This man has pitted keratolysis (PK), characterized by multiple small pits on the soles of the feet. PK is often associated with hyperhidrosis and significant odor. The lesions usually have a punched-out appearance and are flesh-colored. The dark color of these lesions was due to the patient’s footwear.

PK is caused by bacterial overgrowth in the stratum corneum. Corynebacterium is the most common bacterial culprit, but Kytococcus, Actinomyces, and Dermatophilus have also been implicated. The bacterial infection is thought to be secondary to hyperhidrosis or as a result of hygiene, footwear, or other conditions that retain moisture and promote maceration of the soles of the feet. Therefore, treatment includes a 2-pronged approach: Resolve the bacterial infection and reduce excess moisture. Effective antibacterials include topical clindamycin, erythromycin, fusidic acid, and benzoyl peroxide. Oral antibiotics are not often required.

Hyperhidrosis can be treated with prescription strength 20% aluminum chloride antiperspirant applied to the feet in a tapering schedule, first daily and then 2 or 3 times weekly. Aluminum chloride is frequently not covered by insurance companies, but over-the-counter (OTC) 12% formulations (Certain DRI) usually suffice. Additionally, changing socks and using moisture-wicking shoes or socks are helpful measures to keep feet dry.

One study treated PK with topical erythromycin 3% gel twice daily, without the use of aluminum chloride antiperspirants, and found that the hyperhidrosis greatly improved. The authors theorized that the gram-positive bacterial infection upregulated eccrine sweat glands causing hyperhidrosis as a secondary, rather than the primary, cause of PK.

This patient was prescribed topical erythromycin gel twice daily for the soles of his feet. For his hyperhidrosis, he was advised to purchase OTC aluminum chloride antiperspirants to apply to his feet daily for the first week and to then decrease to 2 or 3 times per week. He was counseled to take an extra pair of socks for changing midway through his workday and to return for reevaluation if his skin did not improve.

‌

Image courtesy of Sarah Friedberg, MD, and text courtesy of Daniel Stulberg, MD, FAAFP, and Sarah Friedberg, MD, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This man has pitted keratolysis (PK), characterized by multiple small pits on the soles of the feet. PK is often associated with hyperhidrosis and significant odor. The lesions usually have a punched-out appearance and are flesh-colored. The dark color of these lesions was due to the patient’s footwear.

PK is caused by bacterial overgrowth in the stratum corneum. Corynebacterium is the most common bacterial culprit, but Kytococcus, Actinomyces, and Dermatophilus have also been implicated. The bacterial infection is thought to be secondary to hyperhidrosis or as a result of hygiene, footwear, or other conditions that retain moisture and promote maceration of the soles of the feet. Therefore, treatment includes a 2-pronged approach: Resolve the bacterial infection and reduce excess moisture. Effective antibacterials include topical clindamycin, erythromycin, fusidic acid, and benzoyl peroxide. Oral antibiotics are not often required.

Hyperhidrosis can be treated with prescription strength 20% aluminum chloride antiperspirant applied to the feet in a tapering schedule, first daily and then 2 or 3 times weekly. Aluminum chloride is frequently not covered by insurance companies, but over-the-counter (OTC) 12% formulations (Certain DRI) usually suffice. Additionally, changing socks and using moisture-wicking shoes or socks are helpful measures to keep feet dry.

One study treated PK with topical erythromycin 3% gel twice daily, without the use of aluminum chloride antiperspirants, and found that the hyperhidrosis greatly improved. The authors theorized that the gram-positive bacterial infection upregulated eccrine sweat glands causing hyperhidrosis as a secondary, rather than the primary, cause of PK.

This patient was prescribed topical erythromycin gel twice daily for the soles of his feet. For his hyperhidrosis, he was advised to purchase OTC aluminum chloride antiperspirants to apply to his feet daily for the first week and to then decrease to 2 or 3 times per week. He was counseled to take an extra pair of socks for changing midway through his workday and to return for reevaluation if his skin did not improve.

‌

Image courtesy of Sarah Friedberg, MD, and text courtesy of Daniel Stulberg, MD, FAAFP, and Sarah Friedberg, MD, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This man has pitted keratolysis (PK), characterized by multiple small pits on the soles of the feet. PK is often associated with hyperhidrosis and significant odor. The lesions usually have a punched-out appearance and are flesh-colored. The dark color of these lesions was due to the patient’s footwear.

PK is caused by bacterial overgrowth in the stratum corneum. Corynebacterium is the most common bacterial culprit, but Kytococcus, Actinomyces, and Dermatophilus have also been implicated. The bacterial infection is thought to be secondary to hyperhidrosis or as a result of hygiene, footwear, or other conditions that retain moisture and promote maceration of the soles of the feet. Therefore, treatment includes a 2-pronged approach: Resolve the bacterial infection and reduce excess moisture. Effective antibacterials include topical clindamycin, erythromycin, fusidic acid, and benzoyl peroxide. Oral antibiotics are not often required.

Hyperhidrosis can be treated with prescription strength 20% aluminum chloride antiperspirant applied to the feet in a tapering schedule, first daily and then 2 or 3 times weekly. Aluminum chloride is frequently not covered by insurance companies, but over-the-counter (OTC) 12% formulations (Certain DRI) usually suffice. Additionally, changing socks and using moisture-wicking shoes or socks are helpful measures to keep feet dry.

One study treated PK with topical erythromycin 3% gel twice daily, without the use of aluminum chloride antiperspirants, and found that the hyperhidrosis greatly improved. The authors theorized that the gram-positive bacterial infection upregulated eccrine sweat glands causing hyperhidrosis as a secondary, rather than the primary, cause of PK.

This patient was prescribed topical erythromycin gel twice daily for the soles of his feet. For his hyperhidrosis, he was advised to purchase OTC aluminum chloride antiperspirants to apply to his feet daily for the first week and to then decrease to 2 or 3 times per week. He was counseled to take an extra pair of socks for changing midway through his workday and to return for reevaluation if his skin did not improve.

‌

Image courtesy of Sarah Friedberg, MD, and text courtesy of Daniel Stulberg, MD, FAAFP, and Sarah Friedberg, MD, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This patient had the deep form of erythema annulare centrifugum (EAC). As the name implies, it manifests as an expanding, red circular pattern that often clears in the middle. There is usually a ring of scale that trails behind the advancing border. However, in the deep form, it may be more subtle than the pronounced scale of the superficial form. Pruritus is a very common symptom associated with this condition.

EAC is a hypersensitivity reaction, which can be in response to several stimuli including underlying malignancy, medications, fungal and dermatophyte infections, inflammatory conditions, and pregnancy. A careful history and physical exam can be helpful in determining if a work-up for malignancy is warranted.

Since many medications including nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants, and biologicals can cause this condition, a history of which medications were started within the previous several months may be helpful.

When EAC is due to an underlying malignancy, it is called paraneoplastic erythema annulare centrifugum. It can be secondary to solid tumors or lymphoproliferative disorders.

More than 50% percent of the cases are idiopathic, and no underlying condition is identified. The skin findings may last for weeks—and even years.

If an underlying cause is found, treatment is directed at that condition, and the skin findings usually improve with resolution of the instigating condition. If no specific cause is found, the itching can be managed with systemic antihistamines or topical steroids. Some case studies have reported success with the use of systemic antibiotics, including erythromycin. Improvement with antibiotics may be due to treatment of an occult underlying bacterial process or owing to the anti-inflammatory effects of many antibiotics.

Since the patient in this case had onychomycosis of his toenails, and fungal and dermatophyte infections are a common trigger, he was placed on a 12-week course of oral terbinafine 250 mg/d. The plan was to biopsy the rash if it didn’t resolve. At 3 weeks, the rash had resolved, and the patient was asymptomatic.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This patient had the deep form of erythema annulare centrifugum (EAC). As the name implies, it manifests as an expanding, red circular pattern that often clears in the middle. There is usually a ring of scale that trails behind the advancing border. However, in the deep form, it may be more subtle than the pronounced scale of the superficial form. Pruritus is a very common symptom associated with this condition.

EAC is a hypersensitivity reaction, which can be in response to several stimuli including underlying malignancy, medications, fungal and dermatophyte infections, inflammatory conditions, and pregnancy. A careful history and physical exam can be helpful in determining if a work-up for malignancy is warranted.

Since many medications including nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants, and biologicals can cause this condition, a history of which medications were started within the previous several months may be helpful.

When EAC is due to an underlying malignancy, it is called paraneoplastic erythema annulare centrifugum. It can be secondary to solid tumors or lymphoproliferative disorders.

More than 50% percent of the cases are idiopathic, and no underlying condition is identified. The skin findings may last for weeks—and even years.

If an underlying cause is found, treatment is directed at that condition, and the skin findings usually improve with resolution of the instigating condition. If no specific cause is found, the itching can be managed with systemic antihistamines or topical steroids. Some case studies have reported success with the use of systemic antibiotics, including erythromycin. Improvement with antibiotics may be due to treatment of an occult underlying bacterial process or owing to the anti-inflammatory effects of many antibiotics.

Since the patient in this case had onychomycosis of his toenails, and fungal and dermatophyte infections are a common trigger, he was placed on a 12-week course of oral terbinafine 250 mg/d. The plan was to biopsy the rash if it didn’t resolve. At 3 weeks, the rash had resolved, and the patient was asymptomatic.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This patient had the deep form of erythema annulare centrifugum (EAC). As the name implies, it manifests as an expanding, red circular pattern that often clears in the middle. There is usually a ring of scale that trails behind the advancing border. However, in the deep form, it may be more subtle than the pronounced scale of the superficial form. Pruritus is a very common symptom associated with this condition.

EAC is a hypersensitivity reaction, which can be in response to several stimuli including underlying malignancy, medications, fungal and dermatophyte infections, inflammatory conditions, and pregnancy. A careful history and physical exam can be helpful in determining if a work-up for malignancy is warranted.

Since many medications including nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants, and biologicals can cause this condition, a history of which medications were started within the previous several months may be helpful.

When EAC is due to an underlying malignancy, it is called paraneoplastic erythema annulare centrifugum. It can be secondary to solid tumors or lymphoproliferative disorders.

More than 50% percent of the cases are idiopathic, and no underlying condition is identified. The skin findings may last for weeks—and even years.

If an underlying cause is found, treatment is directed at that condition, and the skin findings usually improve with resolution of the instigating condition. If no specific cause is found, the itching can be managed with systemic antihistamines or topical steroids. Some case studies have reported success with the use of systemic antibiotics, including erythromycin. Improvement with antibiotics may be due to treatment of an occult underlying bacterial process or owing to the anti-inflammatory effects of many antibiotics.

Since the patient in this case had onychomycosis of his toenails, and fungal and dermatophyte infections are a common trigger, he was placed on a 12-week course of oral terbinafine 250 mg/d. The plan was to biopsy the rash if it didn’t resolve. At 3 weeks, the rash had resolved, and the patient was asymptomatic.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

Duvelisib is demonstrating encouraging activity and manageable toxicities among patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) in a phase 2 trial, an investigator said.

The overall response rate in the dose-optimization phase of the PRIMO trial was more than 60% among patients receiving 75 mg of duvelisib twice daily, with a median duration of response exceeding 12 months, said investigator Barbara Pro, MD, of Northwestern University, Chicago.

In the ongoing dose-expansion phase, in which patients start on 75 mg twice daily and then transition to a lower dose, the ORR is over 50%, including complete responses (CRs) in about one-third of patients, Dr. Pro reported at the annual meeting of the American Society of Hematology.

Most previously approved treatments for relapsed/refractory PTCL are associated with ORRs of less than 30%, low rates of CR, and median progression-free survival of less than 4 months, Dr. Pro said in her presentation.

There have been no unexpected toxicities in the dose-expansion phase, and the adverse event profile is consistent with what has been observed previously for this oral phosphatidylinositol 3-kinase (PI3K) inhibitor, according to Dr. Pro.

Based on results to date, Dr. Pro said she and coinvestigators are hopeful that duvelisib will have a place in the treatment armamentarium for relapsed/refractory PTCL in the future.

“This is one of the most effective agents in T-cell lymphoma, and hopefully will be approved and available for treatment soon,” she said in remarks following her presentation of PRIMO study data.

“The next question would be how to try to move this agent up front,” she added. “We’ll have to try to see what could be the possible combinations and evaluate the possible overlapping toxicity with alternative treatments.”

The PRIMO trial provides “very exciting numbers” that include roughly half of relapsed/refractory PTCL patients are responding to the oral therapy, said Andrei R. Shustov, MD, professor of medicine in the division of hematology at the University of Washington, Seattle.

Perhaps more importantly, at least half of those responses have been CRs, Dr. Shustov noted in an interview: “We haven’t seen this yet in T-cell lymphomas, short of brentuximab vedotin targeting CD30,” he said, referring to the 2018 Food and Drug Administration approval of brentuximab vedotin for previously untreated CD30-expressing PTCL.

If duvelisib is approved, it would be the first oral agent with an indication for relapsed/refractory PTCL, which could have important implications for patient quality of life, Dr. Shustov added.

“The fact that you can take a pill at home, and don’t have to be in clinic once a week, or have the port device, or be infused every week would be an incredible change in quality of life,” he said, “and this is really amplified in the older population where quality of life is so important.”

Duvelisib was FDA approved in 2018, at a dose of 25 mg orally twice daily, for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma, and follicular lymphoma, following at least two previous treatments.

In relapsed/refractory PTCL, results of a phase 1 study previously published in Blood showed that duvelisib demonstrated an ORR of 50%, or 8 out of 16 patients treated with 25 or 75 mg twice daily continuously.

The phase 2 study described by Dr. Pro at this year’s ASH meeting included 33 patients with relapsed/refractory PTCL treated with duvelisib 25 mg or 75 mg twice daily as part of a dose-optimization phase, and 25 patients treated in an expansion phase at 75 mg twice daily for two 28-day cycles, followed by treatment at 25 mg twice daily.

Starting at the higher dose of 75 mg twice daily is intended to achieve rapid tumor control, while switching to the lower 25-mg twice-daily dose is to maintain long-term control of the disease while mitigating potential for later toxicities, according to the published abstract for the PRIMO trial.

Results of the dose-optimization phase included an ORR by independent review committee of 62% for patients treated at the 75-mg twice-daily dose, and 40% for those treated at 25 mg twice daily. The median duration of response in the 75-mg twice-daily group was 12.2 months, which Dr. Pro said was significantly higher than what was observed for the lower dose.

In the ongoing dose-expansion phase, the ORR by investigator was 52% (13 of 25 patients), with a CR rate of 36% (9 of 25 patients). The reported data show that with a median duration of follow-up of 3.78 months, the median duration of response thus far is 4.1 months.

The most common grade 3 or higher adverse events were increases in ALT and AST, seen in 24% and 20% of patients, respectively. The most common grade 3 or greater hematologic toxicity was decreased lymphocyte count, seen in 16%.

Three serious treatment-emergent adverse events thought to be related to duvelisib occurred in two patients, including grade 5 pneumonitis in one patient, and skin lesion plus posttransplant lymphoproliferative disorder in the other patient, according to Dr. Pro. Serious treatment-emergent adverse events leading to duvelisib discontinuation included increased ALT/AST in 2 patients and pneumonitis in one patient.

Grade 1-2 adverse events reported at ASH included hypertension, nausea, anemia, fatigue, diarrhea, constipation and pyrexia, among others.

Enrollment in the dose-expansion phase of PRIMO is ongoing and should be complete in February, according to Dr. Pro.

Support for the study came from Verastem Oncology and Secura Bio. Dr. Pro reported research funding from Verastem Oncology, Takeda, and other pharmaceutical companies and honoraria from Takeda and Seattle Genetics.

SOURCE: Pro B et al. ASH 2020, Abstract 44.

Duvelisib is demonstrating encouraging activity and manageable toxicities among patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) in a phase 2 trial, an investigator said.

The overall response rate in the dose-optimization phase of the PRIMO trial was more than 60% among patients receiving 75 mg of duvelisib twice daily, with a median duration of response exceeding 12 months, said investigator Barbara Pro, MD, of Northwestern University, Chicago.

In the ongoing dose-expansion phase, in which patients start on 75 mg twice daily and then transition to a lower dose, the ORR is over 50%, including complete responses (CRs) in about one-third of patients, Dr. Pro reported at the annual meeting of the American Society of Hematology.

Most previously approved treatments for relapsed/refractory PTCL are associated with ORRs of less than 30%, low rates of CR, and median progression-free survival of less than 4 months, Dr. Pro said in her presentation.

There have been no unexpected toxicities in the dose-expansion phase, and the adverse event profile is consistent with what has been observed previously for this oral phosphatidylinositol 3-kinase (PI3K) inhibitor, according to Dr. Pro.

Based on results to date, Dr. Pro said she and coinvestigators are hopeful that duvelisib will have a place in the treatment armamentarium for relapsed/refractory PTCL in the future.

“This is one of the most effective agents in T-cell lymphoma, and hopefully will be approved and available for treatment soon,” she said in remarks following her presentation of PRIMO study data.

“The next question would be how to try to move this agent up front,” she added. “We’ll have to try to see what could be the possible combinations and evaluate the possible overlapping toxicity with alternative treatments.”

The PRIMO trial provides “very exciting numbers” that include roughly half of relapsed/refractory PTCL patients are responding to the oral therapy, said Andrei R. Shustov, MD, professor of medicine in the division of hematology at the University of Washington, Seattle.

Perhaps more importantly, at least half of those responses have been CRs, Dr. Shustov noted in an interview: “We haven’t seen this yet in T-cell lymphomas, short of brentuximab vedotin targeting CD30,” he said, referring to the 2018 Food and Drug Administration approval of brentuximab vedotin for previously untreated CD30-expressing PTCL.

If duvelisib is approved, it would be the first oral agent with an indication for relapsed/refractory PTCL, which could have important implications for patient quality of life, Dr. Shustov added.

“The fact that you can take a pill at home, and don’t have to be in clinic once a week, or have the port device, or be infused every week would be an incredible change in quality of life,” he said, “and this is really amplified in the older population where quality of life is so important.”

Duvelisib was FDA approved in 2018, at a dose of 25 mg orally twice daily, for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma, and follicular lymphoma, following at least two previous treatments.

In relapsed/refractory PTCL, results of a phase 1 study previously published in Blood showed that duvelisib demonstrated an ORR of 50%, or 8 out of 16 patients treated with 25 or 75 mg twice daily continuously.

The phase 2 study described by Dr. Pro at this year’s ASH meeting included 33 patients with relapsed/refractory PTCL treated with duvelisib 25 mg or 75 mg twice daily as part of a dose-optimization phase, and 25 patients treated in an expansion phase at 75 mg twice daily for two 28-day cycles, followed by treatment at 25 mg twice daily.

Starting at the higher dose of 75 mg twice daily is intended to achieve rapid tumor control, while switching to the lower 25-mg twice-daily dose is to maintain long-term control of the disease while mitigating potential for later toxicities, according to the published abstract for the PRIMO trial.

Results of the dose-optimization phase included an ORR by independent review committee of 62% for patients treated at the 75-mg twice-daily dose, and 40% for those treated at 25 mg twice daily. The median duration of response in the 75-mg twice-daily group was 12.2 months, which Dr. Pro said was significantly higher than what was observed for the lower dose.

In the ongoing dose-expansion phase, the ORR by investigator was 52% (13 of 25 patients), with a CR rate of 36% (9 of 25 patients). The reported data show that with a median duration of follow-up of 3.78 months, the median duration of response thus far is 4.1 months.

The most common grade 3 or higher adverse events were increases in ALT and AST, seen in 24% and 20% of patients, respectively. The most common grade 3 or greater hematologic toxicity was decreased lymphocyte count, seen in 16%.

Three serious treatment-emergent adverse events thought to be related to duvelisib occurred in two patients, including grade 5 pneumonitis in one patient, and skin lesion plus posttransplant lymphoproliferative disorder in the other patient, according to Dr. Pro. Serious treatment-emergent adverse events leading to duvelisib discontinuation included increased ALT/AST in 2 patients and pneumonitis in one patient.

Grade 1-2 adverse events reported at ASH included hypertension, nausea, anemia, fatigue, diarrhea, constipation and pyrexia, among others.

Enrollment in the dose-expansion phase of PRIMO is ongoing and should be complete in February, according to Dr. Pro.

Support for the study came from Verastem Oncology and Secura Bio. Dr. Pro reported research funding from Verastem Oncology, Takeda, and other pharmaceutical companies and honoraria from Takeda and Seattle Genetics.

SOURCE: Pro B et al. ASH 2020, Abstract 44.

Duvelisib is demonstrating encouraging activity and manageable toxicities among patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) in a phase 2 trial, an investigator said.

The overall response rate in the dose-optimization phase of the PRIMO trial was more than 60% among patients receiving 75 mg of duvelisib twice daily, with a median duration of response exceeding 12 months, said investigator Barbara Pro, MD, of Northwestern University, Chicago.

In the ongoing dose-expansion phase, in which patients start on 75 mg twice daily and then transition to a lower dose, the ORR is over 50%, including complete responses (CRs) in about one-third of patients, Dr. Pro reported at the annual meeting of the American Society of Hematology.

Most previously approved treatments for relapsed/refractory PTCL are associated with ORRs of less than 30%, low rates of CR, and median progression-free survival of less than 4 months, Dr. Pro said in her presentation.

There have been no unexpected toxicities in the dose-expansion phase, and the adverse event profile is consistent with what has been observed previously for this oral phosphatidylinositol 3-kinase (PI3K) inhibitor, according to Dr. Pro.

Based on results to date, Dr. Pro said she and coinvestigators are hopeful that duvelisib will have a place in the treatment armamentarium for relapsed/refractory PTCL in the future.

“This is one of the most effective agents in T-cell lymphoma, and hopefully will be approved and available for treatment soon,” she said in remarks following her presentation of PRIMO study data.

“The next question would be how to try to move this agent up front,” she added. “We’ll have to try to see what could be the possible combinations and evaluate the possible overlapping toxicity with alternative treatments.”

The PRIMO trial provides “very exciting numbers” that include roughly half of relapsed/refractory PTCL patients are responding to the oral therapy, said Andrei R. Shustov, MD, professor of medicine in the division of hematology at the University of Washington, Seattle.

Perhaps more importantly, at least half of those responses have been CRs, Dr. Shustov noted in an interview: “We haven’t seen this yet in T-cell lymphomas, short of brentuximab vedotin targeting CD30,” he said, referring to the 2018 Food and Drug Administration approval of brentuximab vedotin for previously untreated CD30-expressing PTCL.

If duvelisib is approved, it would be the first oral agent with an indication for relapsed/refractory PTCL, which could have important implications for patient quality of life, Dr. Shustov added.

“The fact that you can take a pill at home, and don’t have to be in clinic once a week, or have the port device, or be infused every week would be an incredible change in quality of life,” he said, “and this is really amplified in the older population where quality of life is so important.”

Duvelisib was FDA approved in 2018, at a dose of 25 mg orally twice daily, for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma, and follicular lymphoma, following at least two previous treatments.

In relapsed/refractory PTCL, results of a phase 1 study previously published in Blood showed that duvelisib demonstrated an ORR of 50%, or 8 out of 16 patients treated with 25 or 75 mg twice daily continuously.

The phase 2 study described by Dr. Pro at this year’s ASH meeting included 33 patients with relapsed/refractory PTCL treated with duvelisib 25 mg or 75 mg twice daily as part of a dose-optimization phase, and 25 patients treated in an expansion phase at 75 mg twice daily for two 28-day cycles, followed by treatment at 25 mg twice daily.

Starting at the higher dose of 75 mg twice daily is intended to achieve rapid tumor control, while switching to the lower 25-mg twice-daily dose is to maintain long-term control of the disease while mitigating potential for later toxicities, according to the published abstract for the PRIMO trial.

Results of the dose-optimization phase included an ORR by independent review committee of 62% for patients treated at the 75-mg twice-daily dose, and 40% for those treated at 25 mg twice daily. The median duration of response in the 75-mg twice-daily group was 12.2 months, which Dr. Pro said was significantly higher than what was observed for the lower dose.

In the ongoing dose-expansion phase, the ORR by investigator was 52% (13 of 25 patients), with a CR rate of 36% (9 of 25 patients). The reported data show that with a median duration of follow-up of 3.78 months, the median duration of response thus far is 4.1 months.

The most common grade 3 or higher adverse events were increases in ALT and AST, seen in 24% and 20% of patients, respectively. The most common grade 3 or greater hematologic toxicity was decreased lymphocyte count, seen in 16%.

Three serious treatment-emergent adverse events thought to be related to duvelisib occurred in two patients, including grade 5 pneumonitis in one patient, and skin lesion plus posttransplant lymphoproliferative disorder in the other patient, according to Dr. Pro. Serious treatment-emergent adverse events leading to duvelisib discontinuation included increased ALT/AST in 2 patients and pneumonitis in one patient.

Grade 1-2 adverse events reported at ASH included hypertension, nausea, anemia, fatigue, diarrhea, constipation and pyrexia, among others.

Enrollment in the dose-expansion phase of PRIMO is ongoing and should be complete in February, according to Dr. Pro.

Support for the study came from Verastem Oncology and Secura Bio. Dr. Pro reported research funding from Verastem Oncology, Takeda, and other pharmaceutical companies and honoraria from Takeda and Seattle Genetics.

SOURCE: Pro B et al. ASH 2020, Abstract 44.

The U.S. Surgeon General and Department of Health & Human Services are calling on health care professionals, hospitals, employers, insurers, women, and the nation to work together to reduce maternal morbidity and mortality – and the disparities that make the risks higher for women of color.

The maternal mortality rate in the United States is the highest among developed countries of the world and continues to rise. In 2018, for every 100,000 live births, approximately 17 women died while pregnant or within 42 days of the end of pregnancy from causes related to pregnancy or delivery – that’s a substantial increase from 7 deaths per 100,000 live births in 1987, according to the surgeon general’s new call to action.

“Our mothers had much lower rates of dying related to pregnancy, compared to women today,” Dorothy Fink, MD, HHS deputy assistant secretary for women’s health, said at a briefing held Dec. 3 to mark the call to action.

Cardiovascular conditions were the most common cause of pregnancy-related deaths between 2011 and 2015, accounting for more than one in three of the deaths. HHS’s related action plan sets a target of achieving blood pressure control in 80% of women of reproductive age with hypertension by 2025.

The plan also seeks to reduce the maternal mortality rate by 50% and decrease low-risk cesarean deliveries by 25% within 5 years.

“A woman dies every 12 hours in this country from pregnancy-related complications,” Surgeon General Jerome Adams, MD, said at the briefing. “This is not just unacceptable, it is just something that we need to understand is not inevitable,” he said, adding that the Centers for Disease Control and Prevention has determined that two thirds of the deaths are preventable.

Dr. Adams also noted that it was important to address maternal health now, especially with COVID-19 raging. “Without attention and action, maternal health could actually worsen because of this pandemic,” he said.

“We cannot discuss maternal health, much less improve it, unless we acknowledge women of color are at a much greater risk of harm related to childbirth,” Dr. Adams said. “Black women are two to three times more likely to die of pregnancy-related causes compared to many other racial and ethnic groups.” The disparity increases with age, according to the CDC.

Studies have shown that education does not eliminate those disparities. Black women with a college degree are twice as likely to die as White or Asian American women who did not finish high school, Dr. Adams said.

He held up a photo of a colleague, Shalone Irving, who he said was a PhD-educated epidemiologist who “died not long ago from pregnancy-related complications.”

Income is also not a factor, said Dr. Adams, noting that pop singer Beyonce had a near-death experience with preeclampsia. He also noted that Serena Williams, a top athlete, also struggled with pregnancy complications.
 

Recommendations not all funded

The HHS action plan is not explicitly funded, although Dr. Fink and Dr. Adams said that President Donald J. Trump’s fiscal 2021 budget includes some specific requests for improving maternal health. It will be up to Congress to grant the requests.

The budget seeks $80 million for the Health Resources and Services Administration to improve access to and quality of care. It also includes money to expand Medicaid coverage for 1 year after birth for women with substance use disorders. The American Medical Association in 2019 adopted a policy urging Medicaid coverage to be expanded to include all women for a year after childbirth. The American College of Obstetricians and Gynecologists has also encouraged this extension.

“We are encouraged that the HHS action plan includes support for policies to close coverage and care gaps for all postpartum women after pregnancy-related Medicaid coverage expires,” Maureen G. Phipps, MD, MPH, CEO of the American College of Obstetricians and Gynecologists, said in an interview.

The HHS could act immediately by approving Medicaid waivers to extend such coverage, Dr. Phipps said.

The budget also requests $24 million to expand maternal mortality review programs to every state, said Dr. Fink. Currently, 43 states and the District of Columbia, have such committees, which are charged with reviewing deaths of women within a year of pregnancy or birth.

The HHS will also join with the March of Dimes to address the disparities in Black women by implementing evidence-based best practices to improve quality in hospital settings.

It is not the first time the Trump administration has taken aim at reducing maternal morbidity and mortality. In 2018, the president signed the Preventing Maternal Deaths Act, which authorized the CDC to award $50 million over 5 years so that every state could form maternal mortality review committees.

A version of this article originally appeared on Medscape.com.

The U.S. Surgeon General and Department of Health & Human Services are calling on health care professionals, hospitals, employers, insurers, women, and the nation to work together to reduce maternal morbidity and mortality – and the disparities that make the risks higher for women of color.

The maternal mortality rate in the United States is the highest among developed countries of the world and continues to rise. In 2018, for every 100,000 live births, approximately 17 women died while pregnant or within 42 days of the end of pregnancy from causes related to pregnancy or delivery – that’s a substantial increase from 7 deaths per 100,000 live births in 1987, according to the surgeon general’s new call to action.

“Our mothers had much lower rates of dying related to pregnancy, compared to women today,” Dorothy Fink, MD, HHS deputy assistant secretary for women’s health, said at a briefing held Dec. 3 to mark the call to action.

Cardiovascular conditions were the most common cause of pregnancy-related deaths between 2011 and 2015, accounting for more than one in three of the deaths. HHS’s related action plan sets a target of achieving blood pressure control in 80% of women of reproductive age with hypertension by 2025.

The plan also seeks to reduce the maternal mortality rate by 50% and decrease low-risk cesarean deliveries by 25% within 5 years.

“A woman dies every 12 hours in this country from pregnancy-related complications,” Surgeon General Jerome Adams, MD, said at the briefing. “This is not just unacceptable, it is just something that we need to understand is not inevitable,” he said, adding that the Centers for Disease Control and Prevention has determined that two thirds of the deaths are preventable.

Dr. Adams also noted that it was important to address maternal health now, especially with COVID-19 raging. “Without attention and action, maternal health could actually worsen because of this pandemic,” he said.

“We cannot discuss maternal health, much less improve it, unless we acknowledge women of color are at a much greater risk of harm related to childbirth,” Dr. Adams said. “Black women are two to three times more likely to die of pregnancy-related causes compared to many other racial and ethnic groups.” The disparity increases with age, according to the CDC.

Studies have shown that education does not eliminate those disparities. Black women with a college degree are twice as likely to die as White or Asian American women who did not finish high school, Dr. Adams said.

He held up a photo of a colleague, Shalone Irving, who he said was a PhD-educated epidemiologist who “died not long ago from pregnancy-related complications.”

Income is also not a factor, said Dr. Adams, noting that pop singer Beyonce had a near-death experience with preeclampsia. He also noted that Serena Williams, a top athlete, also struggled with pregnancy complications.
 

Recommendations not all funded

The HHS action plan is not explicitly funded, although Dr. Fink and Dr. Adams said that President Donald J. Trump’s fiscal 2021 budget includes some specific requests for improving maternal health. It will be up to Congress to grant the requests.

The budget seeks $80 million for the Health Resources and Services Administration to improve access to and quality of care. It also includes money to expand Medicaid coverage for 1 year after birth for women with substance use disorders. The American Medical Association in 2019 adopted a policy urging Medicaid coverage to be expanded to include all women for a year after childbirth. The American College of Obstetricians and Gynecologists has also encouraged this extension.

“We are encouraged that the HHS action plan includes support for policies to close coverage and care gaps for all postpartum women after pregnancy-related Medicaid coverage expires,” Maureen G. Phipps, MD, MPH, CEO of the American College of Obstetricians and Gynecologists, said in an interview.

The HHS could act immediately by approving Medicaid waivers to extend such coverage, Dr. Phipps said.

The budget also requests $24 million to expand maternal mortality review programs to every state, said Dr. Fink. Currently, 43 states and the District of Columbia, have such committees, which are charged with reviewing deaths of women within a year of pregnancy or birth.

The HHS will also join with the March of Dimes to address the disparities in Black women by implementing evidence-based best practices to improve quality in hospital settings.

It is not the first time the Trump administration has taken aim at reducing maternal morbidity and mortality. In 2018, the president signed the Preventing Maternal Deaths Act, which authorized the CDC to award $50 million over 5 years so that every state could form maternal mortality review committees.

A version of this article originally appeared on Medscape.com.

The U.S. Surgeon General and Department of Health & Human Services are calling on health care professionals, hospitals, employers, insurers, women, and the nation to work together to reduce maternal morbidity and mortality – and the disparities that make the risks higher for women of color.

The maternal mortality rate in the United States is the highest among developed countries of the world and continues to rise. In 2018, for every 100,000 live births, approximately 17 women died while pregnant or within 42 days of the end of pregnancy from causes related to pregnancy or delivery – that’s a substantial increase from 7 deaths per 100,000 live births in 1987, according to the surgeon general’s new call to action.

“Our mothers had much lower rates of dying related to pregnancy, compared to women today,” Dorothy Fink, MD, HHS deputy assistant secretary for women’s health, said at a briefing held Dec. 3 to mark the call to action.

Cardiovascular conditions were the most common cause of pregnancy-related deaths between 2011 and 2015, accounting for more than one in three of the deaths. HHS’s related action plan sets a target of achieving blood pressure control in 80% of women of reproductive age with hypertension by 2025.

The plan also seeks to reduce the maternal mortality rate by 50% and decrease low-risk cesarean deliveries by 25% within 5 years.

“A woman dies every 12 hours in this country from pregnancy-related complications,” Surgeon General Jerome Adams, MD, said at the briefing. “This is not just unacceptable, it is just something that we need to understand is not inevitable,” he said, adding that the Centers for Disease Control and Prevention has determined that two thirds of the deaths are preventable.

Dr. Adams also noted that it was important to address maternal health now, especially with COVID-19 raging. “Without attention and action, maternal health could actually worsen because of this pandemic,” he said.

“We cannot discuss maternal health, much less improve it, unless we acknowledge women of color are at a much greater risk of harm related to childbirth,” Dr. Adams said. “Black women are two to three times more likely to die of pregnancy-related causes compared to many other racial and ethnic groups.” The disparity increases with age, according to the CDC.

Studies have shown that education does not eliminate those disparities. Black women with a college degree are twice as likely to die as White or Asian American women who did not finish high school, Dr. Adams said.

He held up a photo of a colleague, Shalone Irving, who he said was a PhD-educated epidemiologist who “died not long ago from pregnancy-related complications.”

Income is also not a factor, said Dr. Adams, noting that pop singer Beyonce had a near-death experience with preeclampsia. He also noted that Serena Williams, a top athlete, also struggled with pregnancy complications.
 

Recommendations not all funded

The HHS action plan is not explicitly funded, although Dr. Fink and Dr. Adams said that President Donald J. Trump’s fiscal 2021 budget includes some specific requests for improving maternal health. It will be up to Congress to grant the requests.

The budget seeks $80 million for the Health Resources and Services Administration to improve access to and quality of care. It also includes money to expand Medicaid coverage for 1 year after birth for women with substance use disorders. The American Medical Association in 2019 adopted a policy urging Medicaid coverage to be expanded to include all women for a year after childbirth. The American College of Obstetricians and Gynecologists has also encouraged this extension.

“We are encouraged that the HHS action plan includes support for policies to close coverage and care gaps for all postpartum women after pregnancy-related Medicaid coverage expires,” Maureen G. Phipps, MD, MPH, CEO of the American College of Obstetricians and Gynecologists, said in an interview.

The HHS could act immediately by approving Medicaid waivers to extend such coverage, Dr. Phipps said.

The budget also requests $24 million to expand maternal mortality review programs to every state, said Dr. Fink. Currently, 43 states and the District of Columbia, have such committees, which are charged with reviewing deaths of women within a year of pregnancy or birth.

The HHS will also join with the March of Dimes to address the disparities in Black women by implementing evidence-based best practices to improve quality in hospital settings.

It is not the first time the Trump administration has taken aim at reducing maternal morbidity and mortality. In 2018, the president signed the Preventing Maternal Deaths Act, which authorized the CDC to award $50 million over 5 years so that every state could form maternal mortality review committees.

A version of this article originally appeared on Medscape.com.

A new analysis of a U.S. national database suggests that surveillance endoscopies are being initiated unnecessarily in patients without a diagnosis of Barrett’s esophagus, and sooner than the recommended interval in patients with nondysplastic Barrett’s esophagus. The study, published in the American Journal of Gastroenterology, found some improvements, suggesting that 2016 recommendations from the American College of Gastroenterology and the American Board of Internal Medicine have had some impact in reducing unnecessary surveillance, but more work may need to be done. The guidelines recommend surveillance of nondysplastic Barrett’s esophagus every 3-5 years, and no biopsy for normal or irregular Z-line (<1 cm of variability).

“There was a notable change in practice after the 2016 ACG guidelines,” said Ziad Gellad, MD, an associate professor of medicine at Duke University, Durham, N.C., in an interview. He noted that fewer providers were recommending 1-2-year surveillance intervals for nondysplastic Barrett’s esophagus and an increase in those who recommended a 3-year interval.

But the study also found frequent biopsies of irregular Z-line. Whether that’s a clear signal of overuse of biopsy is unclear, since the researchers couldn’t determine if other macroscopic or endoscopically visible abnormalities may have been present and driven a decision. “We can’t assume that there wasn’t any other abnormality in the esophagus that deserved to be biopsied,” said Dr. Gellad, who was not involved in the study.

The authors, led by Sachin Wani, MD, of the University of Colorado at Denver, Aurora, and Nicholas J. Shaheen, MD, MPH, of the University of North Carolina at Chapel Hill, analyzed data from the GI Quality Improvement Consortium Registry on 135,704 endoscopies in 114,894 patients, performed between January 2013 and December 2019. Analyzed data included procedure indication, demographics, endoscopy and histology findings, and recommendations for further endoscopy.

Just over 61% of subjects were men, and 91.0% were White. The mean age at time of endoscopy was 61.7 years. 50.2% of procedures produced a pathology-confirmed diagnosis of intestinal metaplasia (IM). Of these, 5.9% were indefinite for dysplasia or low-grade dysplasia (LGD), and 1.5% were high-grade dysplasia (HGD).

In 81.4% of cases with IM and a normal Z-line, the endoscopist recommended surveillance endoscopy. In 44.2%, the repeat was recommended in 3 years. 26.1% were recommended for surveillance in 1-2 years. Surveillance was recommended in 80.7% of cases with IM and an irregular Z-line; 51.5% in 3 years and 19.5% in 1-2 years. Almost 20% of subjects with normal Z-line and no IM were recommended for surveillance endoscopy, most often in 3 years (8.6%). 24% of those with irregular Z-line and no IM were recommended for surveillance endoscopy (15.8% in 3 years). Overall, between 2016 and 2019, compared with 2013-2015, the researchers found an increase in the frequency of recommendation of 3-year intervals, and a decrease in recommendation of 1-2-year intervals.

Among patients with columnar-lined esophagus and confirmed Barrett’s esophagus, 53.4% of the 1- to 3-cm group and 41.8% of the >3-cm group were recommended surveillance endoscopy at 3 years. 21.9% of the 1- to 3-cm group and 30.3% of the >3-cm group were recommended for surveillance endoscopy sooner than 3 years.

“It confirms overuse of upper endoscopy in the management of Barrett’s. However, there is also a nagging question in my mind about what to do about an irregular Z-line,” said Dr. Gellad. He noted that 33.8% of individuals with irregular Z-line had IM, while 3.8% had LGD and 0.7% had HGD. Those patients would have been missed if biopsies had not been taken, which would have been consistent with the new guidelines. However, he noted that pathology findings were not reviewed by an expert pathologist. “Does this data suggest because you find HGD in irregular Z-line, should we now in fact biopsy irregular Z-line? That’s one of the interesting pieces of this,” said Dr. Gellad.

He also believes that there is much more to be learned about what drives the decisions and timing surrounding surveillance endoscopy. “I think that’s an area that’s ripe for research,” said Dr. Gellad.

The study was funded by the University of Colorado department of medicine. The article authors have consulted for various companies. Dr. Gellad has no relevant financial disclosures.

SOURCE: Wani S et al. Am J Gastroenterol. 2020 Oct 11. doi: 10.14309/ajg.0000000000000960.

A new analysis of a U.S. national database suggests that surveillance endoscopies are being initiated unnecessarily in patients without a diagnosis of Barrett’s esophagus, and sooner than the recommended interval in patients with nondysplastic Barrett’s esophagus. The study, published in the American Journal of Gastroenterology, found some improvements, suggesting that 2016 recommendations from the American College of Gastroenterology and the American Board of Internal Medicine have had some impact in reducing unnecessary surveillance, but more work may need to be done. The guidelines recommend surveillance of nondysplastic Barrett’s esophagus every 3-5 years, and no biopsy for normal or irregular Z-line (<1 cm of variability).

“There was a notable change in practice after the 2016 ACG guidelines,” said Ziad Gellad, MD, an associate professor of medicine at Duke University, Durham, N.C., in an interview. He noted that fewer providers were recommending 1-2-year surveillance intervals for nondysplastic Barrett’s esophagus and an increase in those who recommended a 3-year interval.

But the study also found frequent biopsies of irregular Z-line. Whether that’s a clear signal of overuse of biopsy is unclear, since the researchers couldn’t determine if other macroscopic or endoscopically visible abnormalities may have been present and driven a decision. “We can’t assume that there wasn’t any other abnormality in the esophagus that deserved to be biopsied,” said Dr. Gellad, who was not involved in the study.

The authors, led by Sachin Wani, MD, of the University of Colorado at Denver, Aurora, and Nicholas J. Shaheen, MD, MPH, of the University of North Carolina at Chapel Hill, analyzed data from the GI Quality Improvement Consortium Registry on 135,704 endoscopies in 114,894 patients, performed between January 2013 and December 2019. Analyzed data included procedure indication, demographics, endoscopy and histology findings, and recommendations for further endoscopy.

Just over 61% of subjects were men, and 91.0% were White. The mean age at time of endoscopy was 61.7 years. 50.2% of procedures produced a pathology-confirmed diagnosis of intestinal metaplasia (IM). Of these, 5.9% were indefinite for dysplasia or low-grade dysplasia (LGD), and 1.5% were high-grade dysplasia (HGD).

In 81.4% of cases with IM and a normal Z-line, the endoscopist recommended surveillance endoscopy. In 44.2%, the repeat was recommended in 3 years. 26.1% were recommended for surveillance in 1-2 years. Surveillance was recommended in 80.7% of cases with IM and an irregular Z-line; 51.5% in 3 years and 19.5% in 1-2 years. Almost 20% of subjects with normal Z-line and no IM were recommended for surveillance endoscopy, most often in 3 years (8.6%). 24% of those with irregular Z-line and no IM were recommended for surveillance endoscopy (15.8% in 3 years). Overall, between 2016 and 2019, compared with 2013-2015, the researchers found an increase in the frequency of recommendation of 3-year intervals, and a decrease in recommendation of 1-2-year intervals.

Among patients with columnar-lined esophagus and confirmed Barrett’s esophagus, 53.4% of the 1- to 3-cm group and 41.8% of the >3-cm group were recommended surveillance endoscopy at 3 years. 21.9% of the 1- to 3-cm group and 30.3% of the >3-cm group were recommended for surveillance endoscopy sooner than 3 years.

“It confirms overuse of upper endoscopy in the management of Barrett’s. However, there is also a nagging question in my mind about what to do about an irregular Z-line,” said Dr. Gellad. He noted that 33.8% of individuals with irregular Z-line had IM, while 3.8% had LGD and 0.7% had HGD. Those patients would have been missed if biopsies had not been taken, which would have been consistent with the new guidelines. However, he noted that pathology findings were not reviewed by an expert pathologist. “Does this data suggest because you find HGD in irregular Z-line, should we now in fact biopsy irregular Z-line? That’s one of the interesting pieces of this,” said Dr. Gellad.

He also believes that there is much more to be learned about what drives the decisions and timing surrounding surveillance endoscopy. “I think that’s an area that’s ripe for research,” said Dr. Gellad.

The study was funded by the University of Colorado department of medicine. The article authors have consulted for various companies. Dr. Gellad has no relevant financial disclosures.

SOURCE: Wani S et al. Am J Gastroenterol. 2020 Oct 11. doi: 10.14309/ajg.0000000000000960.

A new analysis of a U.S. national database suggests that surveillance endoscopies are being initiated unnecessarily in patients without a diagnosis of Barrett’s esophagus, and sooner than the recommended interval in patients with nondysplastic Barrett’s esophagus. The study, published in the American Journal of Gastroenterology, found some improvements, suggesting that 2016 recommendations from the American College of Gastroenterology and the American Board of Internal Medicine have had some impact in reducing unnecessary surveillance, but more work may need to be done. The guidelines recommend surveillance of nondysplastic Barrett’s esophagus every 3-5 years, and no biopsy for normal or irregular Z-line (<1 cm of variability).

“There was a notable change in practice after the 2016 ACG guidelines,” said Ziad Gellad, MD, an associate professor of medicine at Duke University, Durham, N.C., in an interview. He noted that fewer providers were recommending 1-2-year surveillance intervals for nondysplastic Barrett’s esophagus and an increase in those who recommended a 3-year interval.

But the study also found frequent biopsies of irregular Z-line. Whether that’s a clear signal of overuse of biopsy is unclear, since the researchers couldn’t determine if other macroscopic or endoscopically visible abnormalities may have been present and driven a decision. “We can’t assume that there wasn’t any other abnormality in the esophagus that deserved to be biopsied,” said Dr. Gellad, who was not involved in the study.

The authors, led by Sachin Wani, MD, of the University of Colorado at Denver, Aurora, and Nicholas J. Shaheen, MD, MPH, of the University of North Carolina at Chapel Hill, analyzed data from the GI Quality Improvement Consortium Registry on 135,704 endoscopies in 114,894 patients, performed between January 2013 and December 2019. Analyzed data included procedure indication, demographics, endoscopy and histology findings, and recommendations for further endoscopy.

Just over 61% of subjects were men, and 91.0% were White. The mean age at time of endoscopy was 61.7 years. 50.2% of procedures produced a pathology-confirmed diagnosis of intestinal metaplasia (IM). Of these, 5.9% were indefinite for dysplasia or low-grade dysplasia (LGD), and 1.5% were high-grade dysplasia (HGD).

In 81.4% of cases with IM and a normal Z-line, the endoscopist recommended surveillance endoscopy. In 44.2%, the repeat was recommended in 3 years. 26.1% were recommended for surveillance in 1-2 years. Surveillance was recommended in 80.7% of cases with IM and an irregular Z-line; 51.5% in 3 years and 19.5% in 1-2 years. Almost 20% of subjects with normal Z-line and no IM were recommended for surveillance endoscopy, most often in 3 years (8.6%). 24% of those with irregular Z-line and no IM were recommended for surveillance endoscopy (15.8% in 3 years). Overall, between 2016 and 2019, compared with 2013-2015, the researchers found an increase in the frequency of recommendation of 3-year intervals, and a decrease in recommendation of 1-2-year intervals.

Among patients with columnar-lined esophagus and confirmed Barrett’s esophagus, 53.4% of the 1- to 3-cm group and 41.8% of the >3-cm group were recommended surveillance endoscopy at 3 years. 21.9% of the 1- to 3-cm group and 30.3% of the >3-cm group were recommended for surveillance endoscopy sooner than 3 years.

“It confirms overuse of upper endoscopy in the management of Barrett’s. However, there is also a nagging question in my mind about what to do about an irregular Z-line,” said Dr. Gellad. He noted that 33.8% of individuals with irregular Z-line had IM, while 3.8% had LGD and 0.7% had HGD. Those patients would have been missed if biopsies had not been taken, which would have been consistent with the new guidelines. However, he noted that pathology findings were not reviewed by an expert pathologist. “Does this data suggest because you find HGD in irregular Z-line, should we now in fact biopsy irregular Z-line? That’s one of the interesting pieces of this,” said Dr. Gellad.

He also believes that there is much more to be learned about what drives the decisions and timing surrounding surveillance endoscopy. “I think that’s an area that’s ripe for research,” said Dr. Gellad.

The study was funded by the University of Colorado department of medicine. The article authors have consulted for various companies. Dr. Gellad has no relevant financial disclosures.

SOURCE: Wani S et al. Am J Gastroenterol. 2020 Oct 11. doi: 10.14309/ajg.0000000000000960.

As hematologists debated the role of the anti–von Willebrand factor agent caplacizumab for acquired thrombotic thrombocytopenic purpura (TTP), an investigator on the phase 3 trial that led to its approval had a message.

“If we take finances out” of the picture – a course of treatment is $270,000 – “I think almost every patient except those with a bleeding risk or bleeding problem should get it,” said hematologist Spero Cataland, MD, of the department of internal medicine at Ohio State University in Columbus.

If cost is going to be a factor, and it “has to be in our world these days, it’s more of a discussion,” he said during his presentation at the 2020 Update in Nonneoplastic Hematology virtual conference.

The HERCULES trial Dr. Cataland helped conduct found a median time to platelet count normalization of 2.69 days when caplacizumab was started during plasma exchange versus 2.88 days for placebo; 12% of patients had a TTP recurrence while they continued caplacizumab for 30 days past their last exchange and were followed for an additional 28 days versus 38% randomized to placebo. Caplacizumab subjects needed an average of 5.8 days of plasma exchange versus 9.4 days in the placebo arm (N Engl J Med. 2019 Jan 24;380(4):335-46).

Based on the results, the Food and Drug Administration approved the agent for acquired TTP in combination with plasma exchange and immunosuppressives in Feb. 2019 for 30 days beyond the last plasma exchange, with up to 28 additional days if ADAMTS13 activity remains suppressed. Labeling notes a risk of severe bleeding.

“The data on refractory disease and mortality aren’t quite there yet, but there’s a suggestion [caplacizumab] might impact that as well,” Dr. Cataland said. In its recent TTP guidelines, the International Society on Thrombosis and Haemostasis gave the agent only a conditional recommendation, in part because it’s backed up only by HERCULES and a phase 2 trial.

Also, the group noted that in the phase 2 study caplacizumab patients had a clinically and statistically significant increase in the number of relapses at 12 months: 31% versus 8% placebo. “Caplacizumab may leave patients prone to experience a later recurrence owing to the unresolved ADAMTS13 deficiency and inhibitors,” Dr. Cataland said.

“We do see some early recurrence” when caplacizumab is stopped, suggesting that when the agent’s “protective effect is removed, the risk is still there,” said Dr. Cataland, who was also an author on the ISTH guidelines, as well as the phase 2 trial.

It raises the question of how long patients should be kept on caplacizumab. There are few data on the issue, “but the consensus has been to stop caplacizumab when two consecutive ADAMTS13 measurements show 20% or greater activity,” or perhaps with one reading above 20% in a patient trending in the right direction. “With a bleeding complication, you might stop it sooner,” he said.

Dr. Cataland anticipates TTP management will eventually move away from plasma exchange to more directed therapies, including caplacizumab and perhaps recombinant ADAMTS13, which is in development.

There have been a few reports of TTP patients who refuse plasma exchange on religious grounds being successfully treated with caplacizumab. Dr. Cataland also noted a patient of his with relapsing TTP who didn’t want to be admitted yet again for plasma exchange and steroids at the start of a new episode.

“We managed her with caplacizumab and rituximab, and in a couple weeks she had recovered her ADAMTS13 activity and was able to stop the caplacizumab.” She was a motivated, knowledgeable person, “someone I trusted, so I was comfortable with the approach. I think that may be where we are headed in the future, hopefully,” he said.

Dr. Cataland disclosed research funding and consulting fees from Alexion, caplacizumab’s maker, Sanofi Genzyme, and Takeda,. The conference was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

[email protected]

As hematologists debated the role of the anti–von Willebrand factor agent caplacizumab for acquired thrombotic thrombocytopenic purpura (TTP), an investigator on the phase 3 trial that led to its approval had a message.

“If we take finances out” of the picture – a course of treatment is $270,000 – “I think almost every patient except those with a bleeding risk or bleeding problem should get it,” said hematologist Spero Cataland, MD, of the department of internal medicine at Ohio State University in Columbus.

If cost is going to be a factor, and it “has to be in our world these days, it’s more of a discussion,” he said during his presentation at the 2020 Update in Nonneoplastic Hematology virtual conference.

The HERCULES trial Dr. Cataland helped conduct found a median time to platelet count normalization of 2.69 days when caplacizumab was started during plasma exchange versus 2.88 days for placebo; 12% of patients had a TTP recurrence while they continued caplacizumab for 30 days past their last exchange and were followed for an additional 28 days versus 38% randomized to placebo. Caplacizumab subjects needed an average of 5.8 days of plasma exchange versus 9.4 days in the placebo arm (N Engl J Med. 2019 Jan 24;380(4):335-46).

Based on the results, the Food and Drug Administration approved the agent for acquired TTP in combination with plasma exchange and immunosuppressives in Feb. 2019 for 30 days beyond the last plasma exchange, with up to 28 additional days if ADAMTS13 activity remains suppressed. Labeling notes a risk of severe bleeding.

“The data on refractory disease and mortality aren’t quite there yet, but there’s a suggestion [caplacizumab] might impact that as well,” Dr. Cataland said. In its recent TTP guidelines, the International Society on Thrombosis and Haemostasis gave the agent only a conditional recommendation, in part because it’s backed up only by HERCULES and a phase 2 trial.

Also, the group noted that in the phase 2 study caplacizumab patients had a clinically and statistically significant increase in the number of relapses at 12 months: 31% versus 8% placebo. “Caplacizumab may leave patients prone to experience a later recurrence owing to the unresolved ADAMTS13 deficiency and inhibitors,” Dr. Cataland said.

“We do see some early recurrence” when caplacizumab is stopped, suggesting that when the agent’s “protective effect is removed, the risk is still there,” said Dr. Cataland, who was also an author on the ISTH guidelines, as well as the phase 2 trial.

It raises the question of how long patients should be kept on caplacizumab. There are few data on the issue, “but the consensus has been to stop caplacizumab when two consecutive ADAMTS13 measurements show 20% or greater activity,” or perhaps with one reading above 20% in a patient trending in the right direction. “With a bleeding complication, you might stop it sooner,” he said.

Dr. Cataland anticipates TTP management will eventually move away from plasma exchange to more directed therapies, including caplacizumab and perhaps recombinant ADAMTS13, which is in development.

There have been a few reports of TTP patients who refuse plasma exchange on religious grounds being successfully treated with caplacizumab. Dr. Cataland also noted a patient of his with relapsing TTP who didn’t want to be admitted yet again for plasma exchange and steroids at the start of a new episode.

“We managed her with caplacizumab and rituximab, and in a couple weeks she had recovered her ADAMTS13 activity and was able to stop the caplacizumab.” She was a motivated, knowledgeable person, “someone I trusted, so I was comfortable with the approach. I think that may be where we are headed in the future, hopefully,” he said.

Dr. Cataland disclosed research funding and consulting fees from Alexion, caplacizumab’s maker, Sanofi Genzyme, and Takeda,. The conference was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

[email protected]

As hematologists debated the role of the anti–von Willebrand factor agent caplacizumab for acquired thrombotic thrombocytopenic purpura (TTP), an investigator on the phase 3 trial that led to its approval had a message.

“If we take finances out” of the picture – a course of treatment is $270,000 – “I think almost every patient except those with a bleeding risk or bleeding problem should get it,” said hematologist Spero Cataland, MD, of the department of internal medicine at Ohio State University in Columbus.

If cost is going to be a factor, and it “has to be in our world these days, it’s more of a discussion,” he said during his presentation at the 2020 Update in Nonneoplastic Hematology virtual conference.

The HERCULES trial Dr. Cataland helped conduct found a median time to platelet count normalization of 2.69 days when caplacizumab was started during plasma exchange versus 2.88 days for placebo; 12% of patients had a TTP recurrence while they continued caplacizumab for 30 days past their last exchange and were followed for an additional 28 days versus 38% randomized to placebo. Caplacizumab subjects needed an average of 5.8 days of plasma exchange versus 9.4 days in the placebo arm (N Engl J Med. 2019 Jan 24;380(4):335-46).

Based on the results, the Food and Drug Administration approved the agent for acquired TTP in combination with plasma exchange and immunosuppressives in Feb. 2019 for 30 days beyond the last plasma exchange, with up to 28 additional days if ADAMTS13 activity remains suppressed. Labeling notes a risk of severe bleeding.

“The data on refractory disease and mortality aren’t quite there yet, but there’s a suggestion [caplacizumab] might impact that as well,” Dr. Cataland said. In its recent TTP guidelines, the International Society on Thrombosis and Haemostasis gave the agent only a conditional recommendation, in part because it’s backed up only by HERCULES and a phase 2 trial.

Also, the group noted that in the phase 2 study caplacizumab patients had a clinically and statistically significant increase in the number of relapses at 12 months: 31% versus 8% placebo. “Caplacizumab may leave patients prone to experience a later recurrence owing to the unresolved ADAMTS13 deficiency and inhibitors,” Dr. Cataland said.

“We do see some early recurrence” when caplacizumab is stopped, suggesting that when the agent’s “protective effect is removed, the risk is still there,” said Dr. Cataland, who was also an author on the ISTH guidelines, as well as the phase 2 trial.

It raises the question of how long patients should be kept on caplacizumab. There are few data on the issue, “but the consensus has been to stop caplacizumab when two consecutive ADAMTS13 measurements show 20% or greater activity,” or perhaps with one reading above 20% in a patient trending in the right direction. “With a bleeding complication, you might stop it sooner,” he said.

Dr. Cataland anticipates TTP management will eventually move away from plasma exchange to more directed therapies, including caplacizumab and perhaps recombinant ADAMTS13, which is in development.

There have been a few reports of TTP patients who refuse plasma exchange on religious grounds being successfully treated with caplacizumab. Dr. Cataland also noted a patient of his with relapsing TTP who didn’t want to be admitted yet again for plasma exchange and steroids at the start of a new episode.

“We managed her with caplacizumab and rituximab, and in a couple weeks she had recovered her ADAMTS13 activity and was able to stop the caplacizumab.” She was a motivated, knowledgeable person, “someone I trusted, so I was comfortable with the approach. I think that may be where we are headed in the future, hopefully,” he said.

Dr. Cataland disclosed research funding and consulting fees from Alexion, caplacizumab’s maker, Sanofi Genzyme, and Takeda,. The conference was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

[email protected]

A simple blood test, claimed to detect more than 50 types of cancer, will be used in a pilot trial by National Health Service England in a bid to increase rates of early-stage diagnosis, in particular for cancers that are currently difficult to diagnose.

“Early detection, particularly for hard-to-treat conditions like ovarian and pancreatic cancer, has the potential to save many lives,” said NHS Chief Executive Sir Simon Stevens in a statement.

The pilot trial will use the Galleri blood test, developed by Grail. Sir Stevens described the blood test as “promising” and said it could “be a game changer in cancer care, helping thousands more people to get successful treatment.”

However, some clinicians have expressed concerns over the potential for false-positive results with the test.

Results of a study of the Galleri blood test, published earlier this year, showed that the test detected 50 types of cancer with a specificity of 99.3% and a false positive rate of 0.7%.

It also correctly identified the originating tissue in 90% of cases. However, the sensitivity was lower, at 67%, for the 12 most common cancers, as reported at the time.

The senior author of that study, Michael Seiden, MD, PhD, president of the U.S. Oncology Network, The Woodlands, Tex., noted that it was not a screening study: the test had been used in patients with cancer and in healthy volunteers. He said the test “is intended to be complementary to, and not replace, existing guideline-recommended screening tests and might provide new avenues of investigation for cancers that don’t currently have screening tests.”

The Galleri test uses next-generation sequencing to analyze the arrangement of methyl groups on circulating cell-free DNA in a blood sample.

Several other blood tests for cancer are under development, including the CancerSEEK test, which has been reported to be able to identify eight common cancers. It measures circulating tumor DNA from 16 genes and eight protein biomarkers and then uses machine learning to analyze the data.
 

Improving early detection rates

The pilot trial of the blood test is due to start in mid-2021 and will involve 165,000 people.

The trial will include 140,000 individuals aged 50-79 years who were identified through their health records and who have no cancer symptoms. They will undergo blood tests annually for 3 years and will be referred for investigation if a test result is positive.

A second group will include 25,000 people with potential cancer symptoms. These patients will be offered the blood test to speed up their diagnosis after referral to a hospital via the normal channels.

The results of the pilot are expected in 2023. If successful, the test will be rolled out to 1 million individuals from 2024 to 2025.

The pilot trial is part of the NHS Long Term Plan, which aims to increase early detection of cancer. At present, around half of cancers in England are diagnosed in stage I or II; the NHS aims to increase this to 75% by 2028.

“The NHS has set itself an ambitious target,” commented Peter Johnson, MD, PhD, national clinical director for cancer at NHS England and Improvement.

“Tests like this may help us get there far faster, and I am excited to see how this cutting-edge technology will work out as we test it in clinics across the NHS,” he added.

Lord David Prior, chair of NHS England, noted that almost 200,000 people die from cancer in the United Kingdom every year and that “many of these people are diagnosed too late for treatment to be effective.

“This collaboration between the NHS and Grail offers the chance for a wide range of cancers to be diagnosed much earlier and could fundamentally change the outlook for people with cancer,” he said.

However, some clinicians raised potential concerns.

Stephen Duffy, PhD, Center for Cancer Prevention, Queen Mary University of London, described the pilot as “very exciting,” but cautioned: “We will need to find out just how early the test detects cancers and whether it can it be used in a way which minimizes anxiety from false positives.”

Yong-Jie Lu, MD, PhD, also at Queen Mary University of London, said: “It is not clear how early it aims to catch cancer. For a cancer screen test, it needs very high specificity (>99%), otherwise it may end up in a similar situation as the PSA [prostate-specific antigen] test for prostate cancer, or even worse.”

Mangesh Thorat, MD, Cancer Prevention Trials Unit, King’s College London, warned: “It is likely that for every testing round ... there will be about 1,000 false-positive results, and the test may not be able to pinpoint the location of cancer in 3%-4% of those with a true positive result, necessitating a range of imaging and other investigations in these participants.”

No funding for the study has been declared. The investigators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A simple blood test, claimed to detect more than 50 types of cancer, will be used in a pilot trial by National Health Service England in a bid to increase rates of early-stage diagnosis, in particular for cancers that are currently difficult to diagnose.

“Early detection, particularly for hard-to-treat conditions like ovarian and pancreatic cancer, has the potential to save many lives,” said NHS Chief Executive Sir Simon Stevens in a statement.

The pilot trial will use the Galleri blood test, developed by Grail. Sir Stevens described the blood test as “promising” and said it could “be a game changer in cancer care, helping thousands more people to get successful treatment.”

However, some clinicians have expressed concerns over the potential for false-positive results with the test.

Results of a study of the Galleri blood test, published earlier this year, showed that the test detected 50 types of cancer with a specificity of 99.3% and a false positive rate of 0.7%.

It also correctly identified the originating tissue in 90% of cases. However, the sensitivity was lower, at 67%, for the 12 most common cancers, as reported at the time.

The senior author of that study, Michael Seiden, MD, PhD, president of the U.S. Oncology Network, The Woodlands, Tex., noted that it was not a screening study: the test had been used in patients with cancer and in healthy volunteers. He said the test “is intended to be complementary to, and not replace, existing guideline-recommended screening tests and might provide new avenues of investigation for cancers that don’t currently have screening tests.”

The Galleri test uses next-generation sequencing to analyze the arrangement of methyl groups on circulating cell-free DNA in a blood sample.

Several other blood tests for cancer are under development, including the CancerSEEK test, which has been reported to be able to identify eight common cancers. It measures circulating tumor DNA from 16 genes and eight protein biomarkers and then uses machine learning to analyze the data.
 

Improving early detection rates

The pilot trial of the blood test is due to start in mid-2021 and will involve 165,000 people.

The trial will include 140,000 individuals aged 50-79 years who were identified through their health records and who have no cancer symptoms. They will undergo blood tests annually for 3 years and will be referred for investigation if a test result is positive.

A second group will include 25,000 people with potential cancer symptoms. These patients will be offered the blood test to speed up their diagnosis after referral to a hospital via the normal channels.

The results of the pilot are expected in 2023. If successful, the test will be rolled out to 1 million individuals from 2024 to 2025.

The pilot trial is part of the NHS Long Term Plan, which aims to increase early detection of cancer. At present, around half of cancers in England are diagnosed in stage I or II; the NHS aims to increase this to 75% by 2028.

“The NHS has set itself an ambitious target,” commented Peter Johnson, MD, PhD, national clinical director for cancer at NHS England and Improvement.

“Tests like this may help us get there far faster, and I am excited to see how this cutting-edge technology will work out as we test it in clinics across the NHS,” he added.

Lord David Prior, chair of NHS England, noted that almost 200,000 people die from cancer in the United Kingdom every year and that “many of these people are diagnosed too late for treatment to be effective.

“This collaboration between the NHS and Grail offers the chance for a wide range of cancers to be diagnosed much earlier and could fundamentally change the outlook for people with cancer,” he said.

However, some clinicians raised potential concerns.

Stephen Duffy, PhD, Center for Cancer Prevention, Queen Mary University of London, described the pilot as “very exciting,” but cautioned: “We will need to find out just how early the test detects cancers and whether it can it be used in a way which minimizes anxiety from false positives.”

Yong-Jie Lu, MD, PhD, also at Queen Mary University of London, said: “It is not clear how early it aims to catch cancer. For a cancer screen test, it needs very high specificity (>99%), otherwise it may end up in a similar situation as the PSA [prostate-specific antigen] test for prostate cancer, or even worse.”

Mangesh Thorat, MD, Cancer Prevention Trials Unit, King’s College London, warned: “It is likely that for every testing round ... there will be about 1,000 false-positive results, and the test may not be able to pinpoint the location of cancer in 3%-4% of those with a true positive result, necessitating a range of imaging and other investigations in these participants.”

No funding for the study has been declared. The investigators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A simple blood test, claimed to detect more than 50 types of cancer, will be used in a pilot trial by National Health Service England in a bid to increase rates of early-stage diagnosis, in particular for cancers that are currently difficult to diagnose.

“Early detection, particularly for hard-to-treat conditions like ovarian and pancreatic cancer, has the potential to save many lives,” said NHS Chief Executive Sir Simon Stevens in a statement.

The pilot trial will use the Galleri blood test, developed by Grail. Sir Stevens described the blood test as “promising” and said it could “be a game changer in cancer care, helping thousands more people to get successful treatment.”

However, some clinicians have expressed concerns over the potential for false-positive results with the test.

Results of a study of the Galleri blood test, published earlier this year, showed that the test detected 50 types of cancer with a specificity of 99.3% and a false positive rate of 0.7%.

It also correctly identified the originating tissue in 90% of cases. However, the sensitivity was lower, at 67%, for the 12 most common cancers, as reported at the time.

The senior author of that study, Michael Seiden, MD, PhD, president of the U.S. Oncology Network, The Woodlands, Tex., noted that it was not a screening study: the test had been used in patients with cancer and in healthy volunteers. He said the test “is intended to be complementary to, and not replace, existing guideline-recommended screening tests and might provide new avenues of investigation for cancers that don’t currently have screening tests.”

The Galleri test uses next-generation sequencing to analyze the arrangement of methyl groups on circulating cell-free DNA in a blood sample.

Several other blood tests for cancer are under development, including the CancerSEEK test, which has been reported to be able to identify eight common cancers. It measures circulating tumor DNA from 16 genes and eight protein biomarkers and then uses machine learning to analyze the data.
 

Improving early detection rates

The pilot trial of the blood test is due to start in mid-2021 and will involve 165,000 people.

The trial will include 140,000 individuals aged 50-79 years who were identified through their health records and who have no cancer symptoms. They will undergo blood tests annually for 3 years and will be referred for investigation if a test result is positive.

A second group will include 25,000 people with potential cancer symptoms. These patients will be offered the blood test to speed up their diagnosis after referral to a hospital via the normal channels.

The results of the pilot are expected in 2023. If successful, the test will be rolled out to 1 million individuals from 2024 to 2025.

The pilot trial is part of the NHS Long Term Plan, which aims to increase early detection of cancer. At present, around half of cancers in England are diagnosed in stage I or II; the NHS aims to increase this to 75% by 2028.

“The NHS has set itself an ambitious target,” commented Peter Johnson, MD, PhD, national clinical director for cancer at NHS England and Improvement.

“Tests like this may help us get there far faster, and I am excited to see how this cutting-edge technology will work out as we test it in clinics across the NHS,” he added.

Lord David Prior, chair of NHS England, noted that almost 200,000 people die from cancer in the United Kingdom every year and that “many of these people are diagnosed too late for treatment to be effective.

“This collaboration between the NHS and Grail offers the chance for a wide range of cancers to be diagnosed much earlier and could fundamentally change the outlook for people with cancer,” he said.

However, some clinicians raised potential concerns.

Stephen Duffy, PhD, Center for Cancer Prevention, Queen Mary University of London, described the pilot as “very exciting,” but cautioned: “We will need to find out just how early the test detects cancers and whether it can it be used in a way which minimizes anxiety from false positives.”

Yong-Jie Lu, MD, PhD, also at Queen Mary University of London, said: “It is not clear how early it aims to catch cancer. For a cancer screen test, it needs very high specificity (>99%), otherwise it may end up in a similar situation as the PSA [prostate-specific antigen] test for prostate cancer, or even worse.”

Mangesh Thorat, MD, Cancer Prevention Trials Unit, King’s College London, warned: “It is likely that for every testing round ... there will be about 1,000 false-positive results, and the test may not be able to pinpoint the location of cancer in 3%-4% of those with a true positive result, necessitating a range of imaging and other investigations in these participants.”

No funding for the study has been declared. The investigators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Despite being routinely used in clinical settings, prophylactic use of tranexamic acid, an antifibrinolytic agent administered with platelet transfusions, did not reduce bleeding among patients with blood cancers and severe thrombocytopenia, according to a new study.

The study compared tranexamic acid to placebo and found no significant differences in terms of the number of bleeding events, the number of red blood cell transfusions, or the number of platelet transfusions that were required.

However, the rate of occlusions in the central venous line was significantly higher for patients in the tranexamic acid group, although there was no difference between groups for other types of thrombotic events.

The findings were presented at the annual meeting of the American Society of Hematology, which was held online.

The study was highlighted as potentially practice changing at a press preview webinar by ASH Secretary Robert Brodsky, MD.

“They found absolutely no difference in bleeding or need for transfusion,” said Brodsky. “What they did find was more catheter-associated blood clots in the tranexamic acid group. This is a practice changer in that it probably should not be given prophylactically to patients with thrombocytopenia.”

Senior author Terry B. Gernsheimer, MD, of the University of Washington, Seattle, noted that tranexamic acid has been found to be effective in the treatment of bleeding related to childbirth, surgery, and inherited blood disorders.

It is also used for patients with blood cancers and severe thrombocytopenia. There is little evidence to support this use, which is why the researchers decided to investigate.

“Clearly patients with low platelet counts and blood cancers have a different kind of bleeding than the bleeding experienced by patients who have suffered some kind of trauma or surgery,” Dr. Gernsheimer said in a statement.

“Their bleeding likely is due to endothelial damage – damage to the lining of blood vessels – that tranexamic acid would not treat,” she added.

“To prevent bleeding in these patients, we may need to look at ways to speed the healing of the endothelium that occurs with chemotherapy, radiation, and graft-vs-host disease in patients receiving a transplant,” Dr. Gernsheimer commented.
 

Temper enthusiasm

“Overall, I think these results will temper enthusiasm for using tranexamic acid in this setting,” said Mitul Gandhi, MD, a medical oncologist with Virginia Cancer Specialists, who was approached for comment.

These data do not support the routine use of prophylactic tranexamic acid in chemotherapy-induced thrombocytopenia for patients with platelet counts lower than 30,000/μL, he added.

“The primary objective was not met, and there was an observed increased rate of catheter-associated thrombosis,” he said. “Continued use of judicious transfusion support and correction of a concomitant coagulopathy remains the main clinical approach to these patients.”

Dr. Gandhi commented that tranexamic acid “remains a potentially useful adjunct agent in certain cases of recalcitrant bleeding related to thrombocytopenia or coagulopathy.

“While there is no uniform scenario, it is typically reserved on a case-by-case basis after addressing vascular defects, utilization of platelet, fresh frozen plasma, cryoprecipitate transfusions, vitamin K repletion, and of course excluding any antiplatelet or anticoagulant therapy,» he told this news organization. “For persistent bleeding in spite of all corrective measures or hemorrhage into noncompressible vascular beds, such as with intracranial bleeds, antifibrinolytic therapy may assist in mitigating further blood loss.”

However, this has to be balanced with the potential increased risk for thrombosis after correction of the hemostatic insult.

At present, tranexamic acid “only has an FDA indication for uterine bleeding, but it is frequently used in trauma settings and obstetrical emergencies,” said Douglas Tremblay, MD, an internist at the Icahn School of Medicine at Mount Sinai, New York, who was also approached for comment.

“There is evidence from prior studies that were done 20 or 30 years ago that it may help in this setting, so it is used in some institutions, although we don’t give it prophylactically for patients with a hematologic malignancy.”

Although this was a negative study, Dr. Tremblay pointed out that one thing that may come out of it is that there may be subgroups who can benefit from the prophylactic use of tranexamic acid. “There is very wide inclusion criteria for the study – any type of hematologic malignancy in patients undergoing chemotherapy or stem cell transplant,” he said in an interview. “Even among chemotherapy and transplant patients, there are different risks for bleeding.”

For example, patients undergoing induction chemotherapy for acute myeloid leukemia are at an increased risk of bleeding in comparison with patients with other hematologic malignancies, and those undergoing allogeneic transplant are at an increased risk of bleeding in comparison with patients undergoing autologous transplant. “So while its unclear if a subgroup may benefit from this strategy, lumped together, it doesn’t appear it is of any benefit and potentially harmful, in terms of line occlusions,” he said. “While that may seem to be a nuisance, it can delay chemotherapy or supportive infusions, and that can be a big deal.”
 

No evidence of benefit

Dr. Gernsheimer and colleagues conducted the American Trial Using Tranexamic Acid in Thrombocytopenia (A-TREAT), which evaluated the effects of prophylactic tranexamic acid as an adjunct to routine transfusion therapy on bleeding and transfusion requirements.

A total of 330 patients were randomly assigned to receive either tranexamic acid 1,000 mg IV or 1,300 mg or placebo. Randomization was stratified by site and therapy: chemotherapy, allogeneic transplant, or autologous transplant. It was anticipated that all patients had hypoproliferative thrombocytopenia (expected platelet count, 10,000/µL for at least 5 days).

Treatment continued for 30 days or platelet count recovery (>30,000/µL), diagnosis of thrombosis or veno-occlusive disease, recurrent line occlusion, visible hematuria, or physician or patient request.

The primary endpoint of the study was the proportion of patients with bleeding of World Health Organization grade 2 or above over 30 days after beginning therapy. Secondary endpoints included the number of transfusions and the number of days alive without WHO grade 2+ bleeding during the first 30 days post activation of study drug.

The time to first WHO 2+ bleeding was “remarkably similar” between the tranexamic acid groups and the placebo group, said Dr. Gernsheimer.

In the cohort as a whole, 48.8% in the placebo group experienced a grade 2+ bleed vs. 45.4% in the tranexamic group (odds ratio, 0.86).

Similar results were observed across subgroups: allogeneic transplant, 57.3% vs. 58.8% (OR, 0.94); autologous transplant, 19.9% vs. 24.7% ( OR, 0.71); or chemotherapy, 48% vs. 52.1% (OR, 0.84).

There were no significant differences in mean number of transfusions (difference, 0.1; 95% confidence interval, –1.9 to 2) or days alive without grade 2 or higher bleeding (difference, 0.1; 95% CI, –1.4 to 1.5).

“A post hoc analysis of WHO 3+ bleeding showed these events to be rare and without any improvement with tranexamic acid,” she said.

A higher percentage of patients in the tranexamic acid group experienced thrombotic events (19.5% vs. 11%). “But importantly, in both groups, it was primarily due to central line occlusions without an associated thrombus,” said Dr. Gernsheimer. “This was statistically significant.”

Fewer non–catheter related thrombotic events occurred in the tranexamic acid group (3.7% vs. 5.5%), but the difference was not statistically significant.

There was also no significant difference between groups in veno-occlusive disease after 30 days (1.8% vs. 1.2%) or all-cause mortality at 30 days (2.4% vs. 3%) or 100 days (11.5% vs. 11.5%). No deaths associated with thrombosis had occurred in either group at 120 days.

The study was supported by the University of Washington and the National Heart, Lung, and Blood Institute. Dr. Gernsheimer has relationships with Amgen, Cellphire, Dova Pharmaceuticals, Novartis, Principia, Rigel, Sanofi, and Vertex. Dr. Tremblay and Dr. Gandhi have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Despite being routinely used in clinical settings, prophylactic use of tranexamic acid, an antifibrinolytic agent administered with platelet transfusions, did not reduce bleeding among patients with blood cancers and severe thrombocytopenia, according to a new study.

The study compared tranexamic acid to placebo and found no significant differences in terms of the number of bleeding events, the number of red blood cell transfusions, or the number of platelet transfusions that were required.

However, the rate of occlusions in the central venous line was significantly higher for patients in the tranexamic acid group, although there was no difference between groups for other types of thrombotic events.

The findings were presented at the annual meeting of the American Society of Hematology, which was held online.

The study was highlighted as potentially practice changing at a press preview webinar by ASH Secretary Robert Brodsky, MD.

“They found absolutely no difference in bleeding or need for transfusion,” said Brodsky. “What they did find was more catheter-associated blood clots in the tranexamic acid group. This is a practice changer in that it probably should not be given prophylactically to patients with thrombocytopenia.”

Senior author Terry B. Gernsheimer, MD, of the University of Washington, Seattle, noted that tranexamic acid has been found to be effective in the treatment of bleeding related to childbirth, surgery, and inherited blood disorders.

It is also used for patients with blood cancers and severe thrombocytopenia. There is little evidence to support this use, which is why the researchers decided to investigate.

“Clearly patients with low platelet counts and blood cancers have a different kind of bleeding than the bleeding experienced by patients who have suffered some kind of trauma or surgery,” Dr. Gernsheimer said in a statement.

“Their bleeding likely is due to endothelial damage – damage to the lining of blood vessels – that tranexamic acid would not treat,” she added.

“To prevent bleeding in these patients, we may need to look at ways to speed the healing of the endothelium that occurs with chemotherapy, radiation, and graft-vs-host disease in patients receiving a transplant,” Dr. Gernsheimer commented.
 

Temper enthusiasm

“Overall, I think these results will temper enthusiasm for using tranexamic acid in this setting,” said Mitul Gandhi, MD, a medical oncologist with Virginia Cancer Specialists, who was approached for comment.

These data do not support the routine use of prophylactic tranexamic acid in chemotherapy-induced thrombocytopenia for patients with platelet counts lower than 30,000/μL, he added.

“The primary objective was not met, and there was an observed increased rate of catheter-associated thrombosis,” he said. “Continued use of judicious transfusion support and correction of a concomitant coagulopathy remains the main clinical approach to these patients.”

Dr. Gandhi commented that tranexamic acid “remains a potentially useful adjunct agent in certain cases of recalcitrant bleeding related to thrombocytopenia or coagulopathy.

“While there is no uniform scenario, it is typically reserved on a case-by-case basis after addressing vascular defects, utilization of platelet, fresh frozen plasma, cryoprecipitate transfusions, vitamin K repletion, and of course excluding any antiplatelet or anticoagulant therapy,» he told this news organization. “For persistent bleeding in spite of all corrective measures or hemorrhage into noncompressible vascular beds, such as with intracranial bleeds, antifibrinolytic therapy may assist in mitigating further blood loss.”

However, this has to be balanced with the potential increased risk for thrombosis after correction of the hemostatic insult.

At present, tranexamic acid “only has an FDA indication for uterine bleeding, but it is frequently used in trauma settings and obstetrical emergencies,” said Douglas Tremblay, MD, an internist at the Icahn School of Medicine at Mount Sinai, New York, who was also approached for comment.

“There is evidence from prior studies that were done 20 or 30 years ago that it may help in this setting, so it is used in some institutions, although we don’t give it prophylactically for patients with a hematologic malignancy.”

Although this was a negative study, Dr. Tremblay pointed out that one thing that may come out of it is that there may be subgroups who can benefit from the prophylactic use of tranexamic acid. “There is very wide inclusion criteria for the study – any type of hematologic malignancy in patients undergoing chemotherapy or stem cell transplant,” he said in an interview. “Even among chemotherapy and transplant patients, there are different risks for bleeding.”

For example, patients undergoing induction chemotherapy for acute myeloid leukemia are at an increased risk of bleeding in comparison with patients with other hematologic malignancies, and those undergoing allogeneic transplant are at an increased risk of bleeding in comparison with patients undergoing autologous transplant. “So while its unclear if a subgroup may benefit from this strategy, lumped together, it doesn’t appear it is of any benefit and potentially harmful, in terms of line occlusions,” he said. “While that may seem to be a nuisance, it can delay chemotherapy or supportive infusions, and that can be a big deal.”
 

No evidence of benefit

Dr. Gernsheimer and colleagues conducted the American Trial Using Tranexamic Acid in Thrombocytopenia (A-TREAT), which evaluated the effects of prophylactic tranexamic acid as an adjunct to routine transfusion therapy on bleeding and transfusion requirements.

A total of 330 patients were randomly assigned to receive either tranexamic acid 1,000 mg IV or 1,300 mg or placebo. Randomization was stratified by site and therapy: chemotherapy, allogeneic transplant, or autologous transplant. It was anticipated that all patients had hypoproliferative thrombocytopenia (expected platelet count, 10,000/µL for at least 5 days).

Treatment continued for 30 days or platelet count recovery (>30,000/µL), diagnosis of thrombosis or veno-occlusive disease, recurrent line occlusion, visible hematuria, or physician or patient request.

The primary endpoint of the study was the proportion of patients with bleeding of World Health Organization grade 2 or above over 30 days after beginning therapy. Secondary endpoints included the number of transfusions and the number of days alive without WHO grade 2+ bleeding during the first 30 days post activation of study drug.

The time to first WHO 2+ bleeding was “remarkably similar” between the tranexamic acid groups and the placebo group, said Dr. Gernsheimer.

In the cohort as a whole, 48.8% in the placebo group experienced a grade 2+ bleed vs. 45.4% in the tranexamic group (odds ratio, 0.86).

Similar results were observed across subgroups: allogeneic transplant, 57.3% vs. 58.8% (OR, 0.94); autologous transplant, 19.9% vs. 24.7% ( OR, 0.71); or chemotherapy, 48% vs. 52.1% (OR, 0.84).

There were no significant differences in mean number of transfusions (difference, 0.1; 95% confidence interval, –1.9 to 2) or days alive without grade 2 or higher bleeding (difference, 0.1; 95% CI, –1.4 to 1.5).

“A post hoc analysis of WHO 3+ bleeding showed these events to be rare and without any improvement with tranexamic acid,” she said.

A higher percentage of patients in the tranexamic acid group experienced thrombotic events (19.5% vs. 11%). “But importantly, in both groups, it was primarily due to central line occlusions without an associated thrombus,” said Dr. Gernsheimer. “This was statistically significant.”

Fewer non–catheter related thrombotic events occurred in the tranexamic acid group (3.7% vs. 5.5%), but the difference was not statistically significant.

There was also no significant difference between groups in veno-occlusive disease after 30 days (1.8% vs. 1.2%) or all-cause mortality at 30 days (2.4% vs. 3%) or 100 days (11.5% vs. 11.5%). No deaths associated with thrombosis had occurred in either group at 120 days.

The study was supported by the University of Washington and the National Heart, Lung, and Blood Institute. Dr. Gernsheimer has relationships with Amgen, Cellphire, Dova Pharmaceuticals, Novartis, Principia, Rigel, Sanofi, and Vertex. Dr. Tremblay and Dr. Gandhi have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Despite being routinely used in clinical settings, prophylactic use of tranexamic acid, an antifibrinolytic agent administered with platelet transfusions, did not reduce bleeding among patients with blood cancers and severe thrombocytopenia, according to a new study.

The study compared tranexamic acid to placebo and found no significant differences in terms of the number of bleeding events, the number of red blood cell transfusions, or the number of platelet transfusions that were required.

However, the rate of occlusions in the central venous line was significantly higher for patients in the tranexamic acid group, although there was no difference between groups for other types of thrombotic events.

The findings were presented at the annual meeting of the American Society of Hematology, which was held online.

The study was highlighted as potentially practice changing at a press preview webinar by ASH Secretary Robert Brodsky, MD.

“They found absolutely no difference in bleeding or need for transfusion,” said Brodsky. “What they did find was more catheter-associated blood clots in the tranexamic acid group. This is a practice changer in that it probably should not be given prophylactically to patients with thrombocytopenia.”

Senior author Terry B. Gernsheimer, MD, of the University of Washington, Seattle, noted that tranexamic acid has been found to be effective in the treatment of bleeding related to childbirth, surgery, and inherited blood disorders.

It is also used for patients with blood cancers and severe thrombocytopenia. There is little evidence to support this use, which is why the researchers decided to investigate.

“Clearly patients with low platelet counts and blood cancers have a different kind of bleeding than the bleeding experienced by patients who have suffered some kind of trauma or surgery,” Dr. Gernsheimer said in a statement.

“Their bleeding likely is due to endothelial damage – damage to the lining of blood vessels – that tranexamic acid would not treat,” she added.

“To prevent bleeding in these patients, we may need to look at ways to speed the healing of the endothelium that occurs with chemotherapy, radiation, and graft-vs-host disease in patients receiving a transplant,” Dr. Gernsheimer commented.
 

Temper enthusiasm

“Overall, I think these results will temper enthusiasm for using tranexamic acid in this setting,” said Mitul Gandhi, MD, a medical oncologist with Virginia Cancer Specialists, who was approached for comment.

These data do not support the routine use of prophylactic tranexamic acid in chemotherapy-induced thrombocytopenia for patients with platelet counts lower than 30,000/μL, he added.

“The primary objective was not met, and there was an observed increased rate of catheter-associated thrombosis,” he said. “Continued use of judicious transfusion support and correction of a concomitant coagulopathy remains the main clinical approach to these patients.”

Dr. Gandhi commented that tranexamic acid “remains a potentially useful adjunct agent in certain cases of recalcitrant bleeding related to thrombocytopenia or coagulopathy.

“While there is no uniform scenario, it is typically reserved on a case-by-case basis after addressing vascular defects, utilization of platelet, fresh frozen plasma, cryoprecipitate transfusions, vitamin K repletion, and of course excluding any antiplatelet or anticoagulant therapy,» he told this news organization. “For persistent bleeding in spite of all corrective measures or hemorrhage into noncompressible vascular beds, such as with intracranial bleeds, antifibrinolytic therapy may assist in mitigating further blood loss.”

However, this has to be balanced with the potential increased risk for thrombosis after correction of the hemostatic insult.

At present, tranexamic acid “only has an FDA indication for uterine bleeding, but it is frequently used in trauma settings and obstetrical emergencies,” said Douglas Tremblay, MD, an internist at the Icahn School of Medicine at Mount Sinai, New York, who was also approached for comment.

“There is evidence from prior studies that were done 20 or 30 years ago that it may help in this setting, so it is used in some institutions, although we don’t give it prophylactically for patients with a hematologic malignancy.”

Although this was a negative study, Dr. Tremblay pointed out that one thing that may come out of it is that there may be subgroups who can benefit from the prophylactic use of tranexamic acid. “There is very wide inclusion criteria for the study – any type of hematologic malignancy in patients undergoing chemotherapy or stem cell transplant,” he said in an interview. “Even among chemotherapy and transplant patients, there are different risks for bleeding.”

For example, patients undergoing induction chemotherapy for acute myeloid leukemia are at an increased risk of bleeding in comparison with patients with other hematologic malignancies, and those undergoing allogeneic transplant are at an increased risk of bleeding in comparison with patients undergoing autologous transplant. “So while its unclear if a subgroup may benefit from this strategy, lumped together, it doesn’t appear it is of any benefit and potentially harmful, in terms of line occlusions,” he said. “While that may seem to be a nuisance, it can delay chemotherapy or supportive infusions, and that can be a big deal.”
 

No evidence of benefit

Dr. Gernsheimer and colleagues conducted the American Trial Using Tranexamic Acid in Thrombocytopenia (A-TREAT), which evaluated the effects of prophylactic tranexamic acid as an adjunct to routine transfusion therapy on bleeding and transfusion requirements.

A total of 330 patients were randomly assigned to receive either tranexamic acid 1,000 mg IV or 1,300 mg or placebo. Randomization was stratified by site and therapy: chemotherapy, allogeneic transplant, or autologous transplant. It was anticipated that all patients had hypoproliferative thrombocytopenia (expected platelet count, 10,000/µL for at least 5 days).

Treatment continued for 30 days or platelet count recovery (>30,000/µL), diagnosis of thrombosis or veno-occlusive disease, recurrent line occlusion, visible hematuria, or physician or patient request.

The primary endpoint of the study was the proportion of patients with bleeding of World Health Organization grade 2 or above over 30 days after beginning therapy. Secondary endpoints included the number of transfusions and the number of days alive without WHO grade 2+ bleeding during the first 30 days post activation of study drug.

The time to first WHO 2+ bleeding was “remarkably similar” between the tranexamic acid groups and the placebo group, said Dr. Gernsheimer.

In the cohort as a whole, 48.8% in the placebo group experienced a grade 2+ bleed vs. 45.4% in the tranexamic group (odds ratio, 0.86).

Similar results were observed across subgroups: allogeneic transplant, 57.3% vs. 58.8% (OR, 0.94); autologous transplant, 19.9% vs. 24.7% ( OR, 0.71); or chemotherapy, 48% vs. 52.1% (OR, 0.84).

There were no significant differences in mean number of transfusions (difference, 0.1; 95% confidence interval, –1.9 to 2) or days alive without grade 2 or higher bleeding (difference, 0.1; 95% CI, –1.4 to 1.5).

“A post hoc analysis of WHO 3+ bleeding showed these events to be rare and without any improvement with tranexamic acid,” she said.

A higher percentage of patients in the tranexamic acid group experienced thrombotic events (19.5% vs. 11%). “But importantly, in both groups, it was primarily due to central line occlusions without an associated thrombus,” said Dr. Gernsheimer. “This was statistically significant.”

Fewer non–catheter related thrombotic events occurred in the tranexamic acid group (3.7% vs. 5.5%), but the difference was not statistically significant.

There was also no significant difference between groups in veno-occlusive disease after 30 days (1.8% vs. 1.2%) or all-cause mortality at 30 days (2.4% vs. 3%) or 100 days (11.5% vs. 11.5%). No deaths associated with thrombosis had occurred in either group at 120 days.

The study was supported by the University of Washington and the National Heart, Lung, and Blood Institute. Dr. Gernsheimer has relationships with Amgen, Cellphire, Dova Pharmaceuticals, Novartis, Principia, Rigel, Sanofi, and Vertex. Dr. Tremblay and Dr. Gandhi have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

More than 2 decades on, adult survivors of childhood Hodgkin lymphoma report significantly more neurocognitive impairment than their siblings, but the differences may be related to risk factors in adulthood rather than to treatment in childhood, investigators say.

Among adults with a history of childhood Hodgkin lymphoma and their siblings as controls, the survivors reported significantly worse functioning than their brothers or sisters in four domains of neurocognitive functioning.

In multivariate analysis, however, while sex, race, activity level and smoking status were all significant predictors for worse neurocognitive impairment, there were no significant associations between chemotherapy drugs or chest radiation and neurocognitive impairment, said Annalynn M. Williams, PhD, from St. Jude Children’s Research Hospital in Memphis.

“Hodgkin lymphoma is the most common cancer diagnosed in adolescents, and for many years we’ve had high cure rates, resulting in a growing population of survivors who are now, unfortunately, at an increased risk for cardiovascular, respiratory, endocrine and neurologic late morbidity. The neurocognitive morbidity in this population, however, is unknown,” she said in oral abstract presented at the annual meeting of the American Society of Hematology.
 

Survivors and sibs

To better characterize the potential late neurocognitive effects of intensive Hodgkin lymphoma therapy in childhood, Dr. Williams and colleagues polled survivors of childhood Hodgkin lymphoma and randomly selected sibling controls who were participants in the Childhood Cancer Survivor Study (CCSS).

Participants were asked to complete questionnaires regarding four domains of neurocognitive impairment: task efficiency, emotional regulation, organization, and memory. The investigators defined impairment in each domain as a score lower than that of the 90th percentile of community controls from the St. Jude Lifetime Cohort.

A total of 1,564 survivors and 725 controls completed the questionnaires and were included in the study.

The median age at follow-up was slightly higher among survivors, at 37 versus 32 years. The median age at diagnosis was 14, and the median time since diagnosis was 23 years.

In all, 10.8% of survivors reported impaired task efficiency, compared with 7.7% of controls. Problems with emotional regulation were reported by 16.6% of survivors versus 11.5% of siblings, and difficulties with organization and memory were reported by 12.1% versus10.3%, and 8.1% versus 5.7%, respectively.

In a model adjusted for age, sex, and race, the relative risks for neurocognitive impairment among survivors versus siblings, were as follows: task efficiency (RR,1.37); emotional regulation (RR, 1.56); organization (RR, 1.32); memory (RR, 1.72) (all significant by confidence interval).

In a model adjusted for sex, race, smoking status, exercise, age, time since diagnosis, and treatment exposures, risk factors for neurocognitive impairment among survivors included female versus male sex (significant for emotional regulation and memory deficits); non-White versus White (significant for task efficiency); former smoker versus never (significant for all domains except organization); current smoker versus never (significant for task efficiency and emotional regulation); and meeting Centers for Disease Control and Prevention exercise criteria versus not (negatively significant for task efficiency and organization); (P < .05 for all above comparisons).

However, in a model adjusted for relapse, second malignancy, treatment exposures, age, sex, race, time since diagnosis, smoking status and physical activity, only relapse or second malignancy – surrogates for additional treatment exposures – were significantly associated with neurocognitive impairment, and then only in the domain of task efficiency.

Chronic conditions significantly associated with risk for impairment included cardiovascular disease (significant across all domains), respiratory comorbidities (significant for task efficiency), endocrine disorders (significant for task efficiency), and neurologic disorders (significant in all domains except organization).

“While these analyses give us a sense of the presence of neurocognitive impairment in a large sample of Hodgkin lymphoma survivors from across the U.S., these analyses are limited by the self-reported nature of the data,” Dr. Williams acknowledged.

“Because survivors self-report impairments, these likely represent overt, symptomatic neurocognitive impairments. Many more survivors may experience more subtle neurocognitive impairments, and additional research with objective measures of both chronic health conditions and neurocognitive functioning are warranted,” she added.
 

Smoking gun?

In the question-and-answer session following the presentation, session comoderator Pallawi Torka, MD, from Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., who was not involved in the research, commented that the finding regarding a link between current and former smoking as risk factors for neurocognitive impairment was “intriguing.”

“Do you think that smoking is a cause or an effect of having that impairment in childhood survivors of Hodgkin lymphoma?” she asked.

“That’s a great question, and actually one we have spent a great deal of time discussing, and we’re still trying to tease that apart. We’re still not really sure where that association is coming from,” Dr. Williams replied.

She noted that, in a different sample of CCSS participants from whom biospecimens were collected, the investigators plan to see whether smoking drives inflammation and oxidative stress mechanisms that may be contributing to neurocognitive impairment, or whether smoking is a coping mechanism related to anxiety and depression, which have also been seen in survivors.

Kara Kelly, MD, a pediatric oncologist at Roswell Park, commented that some survivors report symptoms of cognitive dysfunction shortly after treatment, and asked whether there might be a relationship to Hodgkin-specific factors such as B symptoms, in which cytokine-mediated inflammation may play a role.

Dr. Williams said that, “unfortunately, in CCSS these survivors had to be at least 5 years from diagnosis, but in many cases were recruited years after their diagnosis and treatment, so we don’t have data on B symptoms.”

The CCSS is funded by the National Cancer Institute. Dr. Williams, Dr. Palawi, and Dr. Kelly all reported no relevant conflicts of interest to disclose.

SOURCE: Williams AM et al. ASH 2020, Abstract 370.

More than 2 decades on, adult survivors of childhood Hodgkin lymphoma report significantly more neurocognitive impairment than their siblings, but the differences may be related to risk factors in adulthood rather than to treatment in childhood, investigators say.

Among adults with a history of childhood Hodgkin lymphoma and their siblings as controls, the survivors reported significantly worse functioning than their brothers or sisters in four domains of neurocognitive functioning.

In multivariate analysis, however, while sex, race, activity level and smoking status were all significant predictors for worse neurocognitive impairment, there were no significant associations between chemotherapy drugs or chest radiation and neurocognitive impairment, said Annalynn M. Williams, PhD, from St. Jude Children’s Research Hospital in Memphis.

“Hodgkin lymphoma is the most common cancer diagnosed in adolescents, and for many years we’ve had high cure rates, resulting in a growing population of survivors who are now, unfortunately, at an increased risk for cardiovascular, respiratory, endocrine and neurologic late morbidity. The neurocognitive morbidity in this population, however, is unknown,” she said in oral abstract presented at the annual meeting of the American Society of Hematology.
 

Survivors and sibs

To better characterize the potential late neurocognitive effects of intensive Hodgkin lymphoma therapy in childhood, Dr. Williams and colleagues polled survivors of childhood Hodgkin lymphoma and randomly selected sibling controls who were participants in the Childhood Cancer Survivor Study (CCSS).

Participants were asked to complete questionnaires regarding four domains of neurocognitive impairment: task efficiency, emotional regulation, organization, and memory. The investigators defined impairment in each domain as a score lower than that of the 90th percentile of community controls from the St. Jude Lifetime Cohort.

A total of 1,564 survivors and 725 controls completed the questionnaires and were included in the study.

The median age at follow-up was slightly higher among survivors, at 37 versus 32 years. The median age at diagnosis was 14, and the median time since diagnosis was 23 years.

In all, 10.8% of survivors reported impaired task efficiency, compared with 7.7% of controls. Problems with emotional regulation were reported by 16.6% of survivors versus 11.5% of siblings, and difficulties with organization and memory were reported by 12.1% versus10.3%, and 8.1% versus 5.7%, respectively.

In a model adjusted for age, sex, and race, the relative risks for neurocognitive impairment among survivors versus siblings, were as follows: task efficiency (RR,1.37); emotional regulation (RR, 1.56); organization (RR, 1.32); memory (RR, 1.72) (all significant by confidence interval).

In a model adjusted for sex, race, smoking status, exercise, age, time since diagnosis, and treatment exposures, risk factors for neurocognitive impairment among survivors included female versus male sex (significant for emotional regulation and memory deficits); non-White versus White (significant for task efficiency); former smoker versus never (significant for all domains except organization); current smoker versus never (significant for task efficiency and emotional regulation); and meeting Centers for Disease Control and Prevention exercise criteria versus not (negatively significant for task efficiency and organization); (P < .05 for all above comparisons).

However, in a model adjusted for relapse, second malignancy, treatment exposures, age, sex, race, time since diagnosis, smoking status and physical activity, only relapse or second malignancy – surrogates for additional treatment exposures – were significantly associated with neurocognitive impairment, and then only in the domain of task efficiency.

Chronic conditions significantly associated with risk for impairment included cardiovascular disease (significant across all domains), respiratory comorbidities (significant for task efficiency), endocrine disorders (significant for task efficiency), and neurologic disorders (significant in all domains except organization).

“While these analyses give us a sense of the presence of neurocognitive impairment in a large sample of Hodgkin lymphoma survivors from across the U.S., these analyses are limited by the self-reported nature of the data,” Dr. Williams acknowledged.

“Because survivors self-report impairments, these likely represent overt, symptomatic neurocognitive impairments. Many more survivors may experience more subtle neurocognitive impairments, and additional research with objective measures of both chronic health conditions and neurocognitive functioning are warranted,” she added.
 

Smoking gun?

In the question-and-answer session following the presentation, session comoderator Pallawi Torka, MD, from Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., who was not involved in the research, commented that the finding regarding a link between current and former smoking as risk factors for neurocognitive impairment was “intriguing.”

“Do you think that smoking is a cause or an effect of having that impairment in childhood survivors of Hodgkin lymphoma?” she asked.

“That’s a great question, and actually one we have spent a great deal of time discussing, and we’re still trying to tease that apart. We’re still not really sure where that association is coming from,” Dr. Williams replied.

She noted that, in a different sample of CCSS participants from whom biospecimens were collected, the investigators plan to see whether smoking drives inflammation and oxidative stress mechanisms that may be contributing to neurocognitive impairment, or whether smoking is a coping mechanism related to anxiety and depression, which have also been seen in survivors.

Kara Kelly, MD, a pediatric oncologist at Roswell Park, commented that some survivors report symptoms of cognitive dysfunction shortly after treatment, and asked whether there might be a relationship to Hodgkin-specific factors such as B symptoms, in which cytokine-mediated inflammation may play a role.

Dr. Williams said that, “unfortunately, in CCSS these survivors had to be at least 5 years from diagnosis, but in many cases were recruited years after their diagnosis and treatment, so we don’t have data on B symptoms.”

The CCSS is funded by the National Cancer Institute. Dr. Williams, Dr. Palawi, and Dr. Kelly all reported no relevant conflicts of interest to disclose.

SOURCE: Williams AM et al. ASH 2020, Abstract 370.

More than 2 decades on, adult survivors of childhood Hodgkin lymphoma report significantly more neurocognitive impairment than their siblings, but the differences may be related to risk factors in adulthood rather than to treatment in childhood, investigators say.

Among adults with a history of childhood Hodgkin lymphoma and their siblings as controls, the survivors reported significantly worse functioning than their brothers or sisters in four domains of neurocognitive functioning.

In multivariate analysis, however, while sex, race, activity level and smoking status were all significant predictors for worse neurocognitive impairment, there were no significant associations between chemotherapy drugs or chest radiation and neurocognitive impairment, said Annalynn M. Williams, PhD, from St. Jude Children’s Research Hospital in Memphis.

“Hodgkin lymphoma is the most common cancer diagnosed in adolescents, and for many years we’ve had high cure rates, resulting in a growing population of survivors who are now, unfortunately, at an increased risk for cardiovascular, respiratory, endocrine and neurologic late morbidity. The neurocognitive morbidity in this population, however, is unknown,” she said in oral abstract presented at the annual meeting of the American Society of Hematology.
 

Survivors and sibs

To better characterize the potential late neurocognitive effects of intensive Hodgkin lymphoma therapy in childhood, Dr. Williams and colleagues polled survivors of childhood Hodgkin lymphoma and randomly selected sibling controls who were participants in the Childhood Cancer Survivor Study (CCSS).

Participants were asked to complete questionnaires regarding four domains of neurocognitive impairment: task efficiency, emotional regulation, organization, and memory. The investigators defined impairment in each domain as a score lower than that of the 90th percentile of community controls from the St. Jude Lifetime Cohort.

A total of 1,564 survivors and 725 controls completed the questionnaires and were included in the study.

The median age at follow-up was slightly higher among survivors, at 37 versus 32 years. The median age at diagnosis was 14, and the median time since diagnosis was 23 years.

In all, 10.8% of survivors reported impaired task efficiency, compared with 7.7% of controls. Problems with emotional regulation were reported by 16.6% of survivors versus 11.5% of siblings, and difficulties with organization and memory were reported by 12.1% versus10.3%, and 8.1% versus 5.7%, respectively.

In a model adjusted for age, sex, and race, the relative risks for neurocognitive impairment among survivors versus siblings, were as follows: task efficiency (RR,1.37); emotional regulation (RR, 1.56); organization (RR, 1.32); memory (RR, 1.72) (all significant by confidence interval).

In a model adjusted for sex, race, smoking status, exercise, age, time since diagnosis, and treatment exposures, risk factors for neurocognitive impairment among survivors included female versus male sex (significant for emotional regulation and memory deficits); non-White versus White (significant for task efficiency); former smoker versus never (significant for all domains except organization); current smoker versus never (significant for task efficiency and emotional regulation); and meeting Centers for Disease Control and Prevention exercise criteria versus not (negatively significant for task efficiency and organization); (P < .05 for all above comparisons).

However, in a model adjusted for relapse, second malignancy, treatment exposures, age, sex, race, time since diagnosis, smoking status and physical activity, only relapse or second malignancy – surrogates for additional treatment exposures – were significantly associated with neurocognitive impairment, and then only in the domain of task efficiency.

Chronic conditions significantly associated with risk for impairment included cardiovascular disease (significant across all domains), respiratory comorbidities (significant for task efficiency), endocrine disorders (significant for task efficiency), and neurologic disorders (significant in all domains except organization).

“While these analyses give us a sense of the presence of neurocognitive impairment in a large sample of Hodgkin lymphoma survivors from across the U.S., these analyses are limited by the self-reported nature of the data,” Dr. Williams acknowledged.

“Because survivors self-report impairments, these likely represent overt, symptomatic neurocognitive impairments. Many more survivors may experience more subtle neurocognitive impairments, and additional research with objective measures of both chronic health conditions and neurocognitive functioning are warranted,” she added.
 

Smoking gun?

In the question-and-answer session following the presentation, session comoderator Pallawi Torka, MD, from Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., who was not involved in the research, commented that the finding regarding a link between current and former smoking as risk factors for neurocognitive impairment was “intriguing.”

“Do you think that smoking is a cause or an effect of having that impairment in childhood survivors of Hodgkin lymphoma?” she asked.

“That’s a great question, and actually one we have spent a great deal of time discussing, and we’re still trying to tease that apart. We’re still not really sure where that association is coming from,” Dr. Williams replied.

She noted that, in a different sample of CCSS participants from whom biospecimens were collected, the investigators plan to see whether smoking drives inflammation and oxidative stress mechanisms that may be contributing to neurocognitive impairment, or whether smoking is a coping mechanism related to anxiety and depression, which have also been seen in survivors.

Kara Kelly, MD, a pediatric oncologist at Roswell Park, commented that some survivors report symptoms of cognitive dysfunction shortly after treatment, and asked whether there might be a relationship to Hodgkin-specific factors such as B symptoms, in which cytokine-mediated inflammation may play a role.

Dr. Williams said that, “unfortunately, in CCSS these survivors had to be at least 5 years from diagnosis, but in many cases were recruited years after their diagnosis and treatment, so we don’t have data on B symptoms.”

The CCSS is funded by the National Cancer Institute. Dr. Williams, Dr. Palawi, and Dr. Kelly all reported no relevant conflicts of interest to disclose.

SOURCE: Williams AM et al. ASH 2020, Abstract 370.

A majority of hospitals and health care facilities surveyed report operating according to “crisis standards of care” as they struggle to provide sufficient personal protective equipment (PPE).

For example, in a national survey, 73% of 1,083 infection prevention experts said respirator shortages related to care for patients with COVID-19 drove their facility to move beyond conventional standards of care. Furthermore, 69% of facilities are using crisis standards of care (CSC) to provide masks, and 76% are apportioning face shields or eye protection.

Almost 76% of respondents who report reusing respirators said their facility allows them to use each respirator either five times or as many times as possible before replacement; 74% allow similar reuse of masks.

Although the majority of institutions remain in this crisis mode, many health care providers have better access to PPE than they did in the spring 2020, the Association for Professionals in Infection Control and Epidemiology (APIC) noted in its latest national survey.

“It is disheartening to see our healthcare system strained and implementing PPE crisis standards of care more than eight months into the pandemic,” APIC President Connie Steed, MSN, RN, said in a December 3 news release.

The association surveyed experts online between Oct. 22 and Nov. 5. The survey was timed to gauge the extent of resource shortages as COVID-19 cases increase and the 2020-2021 flu season begins.

“Many of us on the front lines are waiting for the other shoe to drop. With the upcoming flu season, we implore people to do what they can to keep safe, protect our healthcare personnel, and lessen the strain on our health care system,” Ms. Steed said.
 

COVID-19 linked to more infections, too

APIC also asked infection prevention specialists about changes in health care–associated infection rates since the onset of the pandemic. The experts reported an almost 28% increase in central line–associated bloodstream infections and 21% more catheter-associated urinary tract infections. They also reported an 18% rise in ventilator-associated pneumonia or ventilator-associated events, compared with before the COVID-19 pandemic.

This is the second PPE survey the APIC has conducted during the pandemic. The organization first reported a dire situation in March. For example, the initial survey found that 48% of facilities were almost out or were out of respirators used to care for patients with COVID-19.

This article first appeared on Medscape.com.

A majority of hospitals and health care facilities surveyed report operating according to “crisis standards of care” as they struggle to provide sufficient personal protective equipment (PPE).

For example, in a national survey, 73% of 1,083 infection prevention experts said respirator shortages related to care for patients with COVID-19 drove their facility to move beyond conventional standards of care. Furthermore, 69% of facilities are using crisis standards of care (CSC) to provide masks, and 76% are apportioning face shields or eye protection.

Almost 76% of respondents who report reusing respirators said their facility allows them to use each respirator either five times or as many times as possible before replacement; 74% allow similar reuse of masks.

Although the majority of institutions remain in this crisis mode, many health care providers have better access to PPE than they did in the spring 2020, the Association for Professionals in Infection Control and Epidemiology (APIC) noted in its latest national survey.

“It is disheartening to see our healthcare system strained and implementing PPE crisis standards of care more than eight months into the pandemic,” APIC President Connie Steed, MSN, RN, said in a December 3 news release.

The association surveyed experts online between Oct. 22 and Nov. 5. The survey was timed to gauge the extent of resource shortages as COVID-19 cases increase and the 2020-2021 flu season begins.

“Many of us on the front lines are waiting for the other shoe to drop. With the upcoming flu season, we implore people to do what they can to keep safe, protect our healthcare personnel, and lessen the strain on our health care system,” Ms. Steed said.
 

COVID-19 linked to more infections, too

APIC also asked infection prevention specialists about changes in health care–associated infection rates since the onset of the pandemic. The experts reported an almost 28% increase in central line–associated bloodstream infections and 21% more catheter-associated urinary tract infections. They also reported an 18% rise in ventilator-associated pneumonia or ventilator-associated events, compared with before the COVID-19 pandemic.

This is the second PPE survey the APIC has conducted during the pandemic. The organization first reported a dire situation in March. For example, the initial survey found that 48% of facilities were almost out or were out of respirators used to care for patients with COVID-19.

This article first appeared on Medscape.com.

A majority of hospitals and health care facilities surveyed report operating according to “crisis standards of care” as they struggle to provide sufficient personal protective equipment (PPE).

For example, in a national survey, 73% of 1,083 infection prevention experts said respirator shortages related to care for patients with COVID-19 drove their facility to move beyond conventional standards of care. Furthermore, 69% of facilities are using crisis standards of care (CSC) to provide masks, and 76% are apportioning face shields or eye protection.

Almost 76% of respondents who report reusing respirators said their facility allows them to use each respirator either five times or as many times as possible before replacement; 74% allow similar reuse of masks.

Although the majority of institutions remain in this crisis mode, many health care providers have better access to PPE than they did in the spring 2020, the Association for Professionals in Infection Control and Epidemiology (APIC) noted in its latest national survey.

“It is disheartening to see our healthcare system strained and implementing PPE crisis standards of care more than eight months into the pandemic,” APIC President Connie Steed, MSN, RN, said in a December 3 news release.

The association surveyed experts online between Oct. 22 and Nov. 5. The survey was timed to gauge the extent of resource shortages as COVID-19 cases increase and the 2020-2021 flu season begins.

“Many of us on the front lines are waiting for the other shoe to drop. With the upcoming flu season, we implore people to do what they can to keep safe, protect our healthcare personnel, and lessen the strain on our health care system,” Ms. Steed said.
 

COVID-19 linked to more infections, too

APIC also asked infection prevention specialists about changes in health care–associated infection rates since the onset of the pandemic. The experts reported an almost 28% increase in central line–associated bloodstream infections and 21% more catheter-associated urinary tract infections. They also reported an 18% rise in ventilator-associated pneumonia or ventilator-associated events, compared with before the COVID-19 pandemic.

This is the second PPE survey the APIC has conducted during the pandemic. The organization first reported a dire situation in March. For example, the initial survey found that 48% of facilities were almost out or were out of respirators used to care for patients with COVID-19.

This article first appeared on Medscape.com.