SAN FRANCISCO – Children diagnosed with atopic dermatitis when they were 1 year old were significantly more likely to have active food allergies and to have those allergies persist throughout childhood to age 18 years, based on findings from a prospective, longitudinal study of 287 Wisconsin children.

Mitchel L. Zoler/MDedge News

The link between atopic dermatitis (AD) and food allergy was especially strong in children who displayed early and recurrent AD; the link was weaker or essentially nonexistent for children with early transient AD or AD that first appeared later in childhood, Anne Marie Singh, MD, said while presenting a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The results also showed that even mild AD linked with an increased prevalence of food allergy when it appeared early and persisted, but more severe AD with this onset and recurrence pattern led to an even greater prevalence of food allergy, said Dr. Singh, a pediatric allergist and asthma specialist at the University of Wisconsin–Madison.

“The data suggest that something about early, recurrent AD increases the risk for food allergy throughout childhood,” Dr. Singh said in an interview. The findings suggest that surveillance for food allergies need to be intensified in infants who present with AD by the time they’re 1 year old and that food allergy surveillance should continue as these children age as long as their AD recurs.

The results also hint that these children might potentially benefit from steps aimed at desensitizing the allergy, although this must be proven in a future intervention study, she said.

The results suggest that a food allergy prevention regimen like the one used in the Learning Early About Peanut Allergy (LEAP) trial (New Engl J Med. 2015 Feb 26;372[9]:803-13) to prevent peanut allergy may be appropriate for selected, high-risk children with early AD, but this hypothesis needs testing, Dr. Singh said. She noted that some important differences exist between the patients enrolled in LEAP and the children studied in the current report: In LEAP, all enrolled children had severe eczema, an established egg allergy, or both. The findings reported by Dr. Singh came from children with AD, but only about 30% had moderate or severe eczema, and her analysis did not subdivide the observed food allergies by the type of food that caused a reaction.

She and her associates used data collected in the Childhood Origins of Asthma (COAST) study, begun in 1998, which enrolled 287 infants prior to birth who had at least one parent who was allergic, asthmatic, or both (Pediatr Allergy Immunol. 2002 Dec;13[s15]:38-43). The data showed that 62% of the infants had either no AD or transient AD, 14% had late onset AD, and 24% had early, recurrent AD. Although the data showed a statistically significant link between AD at 1 year old and food allergies throughout childhood, further analysis that broke the population into three different patterns of AD showed that the link with food allergy primarily existed among children with the early, recurrent form. Children with early, recurrent atopic dermatitis had a food allergy prevalence of 12%-27% annually through the age of 18 years.

“The data suggest that immunologic changes early in life are critical to food allergy development and that these changes have long-lasting effects throughout childhood,” Dr. Singh concluded. “The immunologic mechanisms by which early AD affects food allergy development and disease expression require further investigation.”

COAST received no commercial funding. Dr. Singh reported no relevant financial disclosures.

[email protected]

SOURCE: Singh AM et al. J Allergy Clin Immunol. 2019 Feb;143[2]:AB125.

SAN FRANCISCO – Children diagnosed with atopic dermatitis when they were 1 year old were significantly more likely to have active food allergies and to have those allergies persist throughout childhood to age 18 years, based on findings from a prospective, longitudinal study of 287 Wisconsin children.

Mitchel L. Zoler/MDedge News

The link between atopic dermatitis (AD) and food allergy was especially strong in children who displayed early and recurrent AD; the link was weaker or essentially nonexistent for children with early transient AD or AD that first appeared later in childhood, Anne Marie Singh, MD, said while presenting a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The results also showed that even mild AD linked with an increased prevalence of food allergy when it appeared early and persisted, but more severe AD with this onset and recurrence pattern led to an even greater prevalence of food allergy, said Dr. Singh, a pediatric allergist and asthma specialist at the University of Wisconsin–Madison.

“The data suggest that something about early, recurrent AD increases the risk for food allergy throughout childhood,” Dr. Singh said in an interview. The findings suggest that surveillance for food allergies need to be intensified in infants who present with AD by the time they’re 1 year old and that food allergy surveillance should continue as these children age as long as their AD recurs.

The results also hint that these children might potentially benefit from steps aimed at desensitizing the allergy, although this must be proven in a future intervention study, she said.

The results suggest that a food allergy prevention regimen like the one used in the Learning Early About Peanut Allergy (LEAP) trial (New Engl J Med. 2015 Feb 26;372[9]:803-13) to prevent peanut allergy may be appropriate for selected, high-risk children with early AD, but this hypothesis needs testing, Dr. Singh said. She noted that some important differences exist between the patients enrolled in LEAP and the children studied in the current report: In LEAP, all enrolled children had severe eczema, an established egg allergy, or both. The findings reported by Dr. Singh came from children with AD, but only about 30% had moderate or severe eczema, and her analysis did not subdivide the observed food allergies by the type of food that caused a reaction.

She and her associates used data collected in the Childhood Origins of Asthma (COAST) study, begun in 1998, which enrolled 287 infants prior to birth who had at least one parent who was allergic, asthmatic, or both (Pediatr Allergy Immunol. 2002 Dec;13[s15]:38-43). The data showed that 62% of the infants had either no AD or transient AD, 14% had late onset AD, and 24% had early, recurrent AD. Although the data showed a statistically significant link between AD at 1 year old and food allergies throughout childhood, further analysis that broke the population into three different patterns of AD showed that the link with food allergy primarily existed among children with the early, recurrent form. Children with early, recurrent atopic dermatitis had a food allergy prevalence of 12%-27% annually through the age of 18 years.

“The data suggest that immunologic changes early in life are critical to food allergy development and that these changes have long-lasting effects throughout childhood,” Dr. Singh concluded. “The immunologic mechanisms by which early AD affects food allergy development and disease expression require further investigation.”

COAST received no commercial funding. Dr. Singh reported no relevant financial disclosures.

[email protected]

SOURCE: Singh AM et al. J Allergy Clin Immunol. 2019 Feb;143[2]:AB125.

SAN FRANCISCO – Children diagnosed with atopic dermatitis when they were 1 year old were significantly more likely to have active food allergies and to have those allergies persist throughout childhood to age 18 years, based on findings from a prospective, longitudinal study of 287 Wisconsin children.

Mitchel L. Zoler/MDedge News

The link between atopic dermatitis (AD) and food allergy was especially strong in children who displayed early and recurrent AD; the link was weaker or essentially nonexistent for children with early transient AD or AD that first appeared later in childhood, Anne Marie Singh, MD, said while presenting a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The results also showed that even mild AD linked with an increased prevalence of food allergy when it appeared early and persisted, but more severe AD with this onset and recurrence pattern led to an even greater prevalence of food allergy, said Dr. Singh, a pediatric allergist and asthma specialist at the University of Wisconsin–Madison.

“The data suggest that something about early, recurrent AD increases the risk for food allergy throughout childhood,” Dr. Singh said in an interview. The findings suggest that surveillance for food allergies need to be intensified in infants who present with AD by the time they’re 1 year old and that food allergy surveillance should continue as these children age as long as their AD recurs.

The results also hint that these children might potentially benefit from steps aimed at desensitizing the allergy, although this must be proven in a future intervention study, she said.

The results suggest that a food allergy prevention regimen like the one used in the Learning Early About Peanut Allergy (LEAP) trial (New Engl J Med. 2015 Feb 26;372[9]:803-13) to prevent peanut allergy may be appropriate for selected, high-risk children with early AD, but this hypothesis needs testing, Dr. Singh said. She noted that some important differences exist between the patients enrolled in LEAP and the children studied in the current report: In LEAP, all enrolled children had severe eczema, an established egg allergy, or both. The findings reported by Dr. Singh came from children with AD, but only about 30% had moderate or severe eczema, and her analysis did not subdivide the observed food allergies by the type of food that caused a reaction.

She and her associates used data collected in the Childhood Origins of Asthma (COAST) study, begun in 1998, which enrolled 287 infants prior to birth who had at least one parent who was allergic, asthmatic, or both (Pediatr Allergy Immunol. 2002 Dec;13[s15]:38-43). The data showed that 62% of the infants had either no AD or transient AD, 14% had late onset AD, and 24% had early, recurrent AD. Although the data showed a statistically significant link between AD at 1 year old and food allergies throughout childhood, further analysis that broke the population into three different patterns of AD showed that the link with food allergy primarily existed among children with the early, recurrent form. Children with early, recurrent atopic dermatitis had a food allergy prevalence of 12%-27% annually through the age of 18 years.

“The data suggest that immunologic changes early in life are critical to food allergy development and that these changes have long-lasting effects throughout childhood,” Dr. Singh concluded. “The immunologic mechanisms by which early AD affects food allergy development and disease expression require further investigation.”

COAST received no commercial funding. Dr. Singh reported no relevant financial disclosures.

[email protected]

SOURCE: Singh AM et al. J Allergy Clin Immunol. 2019 Feb;143[2]:AB125.

Patients who test positive on a fecal immunochemical test (FIT), even after a recent colonoscopy, should be offered a repeat colonoscopy. That is the conclusion following a review of 2,228 subjects who were FIT positive, which revealed a greater risk of colorectal cancer (CRC) and advanced colo-rectal neoplasia (ACRN) the longer the gap since the last colonoscopy. The findings support the recommendations of the U.S. Multi-Society Task Force on CRC Screening to offer repeat colonoscopies to FIT-positive patients, even if they recently underwent a colonoscopy.

pixologicstudio/Thinkstock

That recommendation was based on low-quality supporting evidence, and there is currently little agreement about whether annual FIT should be performed along with colonoscopy.

The researchers set out to detect the frequency of CRC and ACRN among patients with a positive FIT test. They analyzed data from the National Cancer Screening Program in Korea, which offers an annual FIT for adults aged 50 years and older as an initial screening, followed by a colonoscopy in case of a positive result.

The researchers analyzed data from 52,376 individuals who underwent FIT at a single center in Korea during January 2013–July 2017. They excluded patients with a history of CRC or colorectal surgery, inflammatory bowel disease, or poor bowel preparation.

FIT-positive and FIT-negative patients were divided into three groups based on the length of time since their last colonoscopy: less than 3 years, 3-10 years, or more than 10 years or no colonoscopy.

Compared with FIT-negative subjects, FIT-positive individuals were more likely to be diagnosed with any colorectal neoplasia (61.3% vs. 51.8%; P less than .001), ACRN (20.0% vs. 10.3%; P less than .001), and CRC (5.0% vs. 1.9%; P less than .001).

A total of 6% of subjects had a positive FIT result, and data from 2,228 were analyzed after exclusions. They were compared with 6,135 participants who had negative FIT results but underwent a colonoscopy.

Of patients with a positive FIT result, 23.1% had a colonoscopy less than 3 years before, 19.2% had one 3-10 years prior, and 57.8% had a colonoscopy more than 10 years earlier or had never had one.

March is Colorectal Cancer Awareness Month. AGA is here to help with patient education materials and a new video series. Visit http://crcawareness.gastro.org/ to access all the resources and share on your practice website and social media channels.

SOURCE: Kim NH et al. Gastrointest Endosc. 2019 Jan 23. doi: 10.1016/j.gie.2019.01.012.

Patients who test positive on a fecal immunochemical test (FIT), even after a recent colonoscopy, should be offered a repeat colonoscopy. That is the conclusion following a review of 2,228 subjects who were FIT positive, which revealed a greater risk of colorectal cancer (CRC) and advanced colo-rectal neoplasia (ACRN) the longer the gap since the last colonoscopy. The findings support the recommendations of the U.S. Multi-Society Task Force on CRC Screening to offer repeat colonoscopies to FIT-positive patients, even if they recently underwent a colonoscopy.

pixologicstudio/Thinkstock

That recommendation was based on low-quality supporting evidence, and there is currently little agreement about whether annual FIT should be performed along with colonoscopy.

The researchers set out to detect the frequency of CRC and ACRN among patients with a positive FIT test. They analyzed data from the National Cancer Screening Program in Korea, which offers an annual FIT for adults aged 50 years and older as an initial screening, followed by a colonoscopy in case of a positive result.

The researchers analyzed data from 52,376 individuals who underwent FIT at a single center in Korea during January 2013–July 2017. They excluded patients with a history of CRC or colorectal surgery, inflammatory bowel disease, or poor bowel preparation.

FIT-positive and FIT-negative patients were divided into three groups based on the length of time since their last colonoscopy: less than 3 years, 3-10 years, or more than 10 years or no colonoscopy.

Compared with FIT-negative subjects, FIT-positive individuals were more likely to be diagnosed with any colorectal neoplasia (61.3% vs. 51.8%; P less than .001), ACRN (20.0% vs. 10.3%; P less than .001), and CRC (5.0% vs. 1.9%; P less than .001).

A total of 6% of subjects had a positive FIT result, and data from 2,228 were analyzed after exclusions. They were compared with 6,135 participants who had negative FIT results but underwent a colonoscopy.

Of patients with a positive FIT result, 23.1% had a colonoscopy less than 3 years before, 19.2% had one 3-10 years prior, and 57.8% had a colonoscopy more than 10 years earlier or had never had one.

March is Colorectal Cancer Awareness Month. AGA is here to help with patient education materials and a new video series. Visit http://crcawareness.gastro.org/ to access all the resources and share on your practice website and social media channels.

SOURCE: Kim NH et al. Gastrointest Endosc. 2019 Jan 23. doi: 10.1016/j.gie.2019.01.012.

Patients who test positive on a fecal immunochemical test (FIT), even after a recent colonoscopy, should be offered a repeat colonoscopy. That is the conclusion following a review of 2,228 subjects who were FIT positive, which revealed a greater risk of colorectal cancer (CRC) and advanced colo-rectal neoplasia (ACRN) the longer the gap since the last colonoscopy. The findings support the recommendations of the U.S. Multi-Society Task Force on CRC Screening to offer repeat colonoscopies to FIT-positive patients, even if they recently underwent a colonoscopy.

pixologicstudio/Thinkstock

That recommendation was based on low-quality supporting evidence, and there is currently little agreement about whether annual FIT should be performed along with colonoscopy.

The researchers set out to detect the frequency of CRC and ACRN among patients with a positive FIT test. They analyzed data from the National Cancer Screening Program in Korea, which offers an annual FIT for adults aged 50 years and older as an initial screening, followed by a colonoscopy in case of a positive result.

The researchers analyzed data from 52,376 individuals who underwent FIT at a single center in Korea during January 2013–July 2017. They excluded patients with a history of CRC or colorectal surgery, inflammatory bowel disease, or poor bowel preparation.

FIT-positive and FIT-negative patients were divided into three groups based on the length of time since their last colonoscopy: less than 3 years, 3-10 years, or more than 10 years or no colonoscopy.

Compared with FIT-negative subjects, FIT-positive individuals were more likely to be diagnosed with any colorectal neoplasia (61.3% vs. 51.8%; P less than .001), ACRN (20.0% vs. 10.3%; P less than .001), and CRC (5.0% vs. 1.9%; P less than .001).

A total of 6% of subjects had a positive FIT result, and data from 2,228 were analyzed after exclusions. They were compared with 6,135 participants who had negative FIT results but underwent a colonoscopy.

Of patients with a positive FIT result, 23.1% had a colonoscopy less than 3 years before, 19.2% had one 3-10 years prior, and 57.8% had a colonoscopy more than 10 years earlier or had never had one.

March is Colorectal Cancer Awareness Month. AGA is here to help with patient education materials and a new video series. Visit http://crcawareness.gastro.org/ to access all the resources and share on your practice website and social media channels.

SOURCE: Kim NH et al. Gastrointest Endosc. 2019 Jan 23. doi: 10.1016/j.gie.2019.01.012.

HOUSTON – Ixazomib may reduce treatment failure in patients with advanced chronic graft-versus-host disease (cGVHD), findings from a phase 2 trial suggest.

Patients who received ixazomib in this trial had a lower rate of treatment failure – a composite endpoint of death, relapse, and need for additional systemic immunosuppressive therapy – than that of historical controls.

Joseph Pidala, MD, PhD, of Moffitt Cancer Center in Tampa, Fla., presented this finding at the Transplantation & Cellular Therapy Meetings.

The trial (NCT02513498) included 50 patients with a median age of 58 years (range, 44-65). Patients had acute leukemia (52%), lymphoma (18%), chronic leukemia (12%), myelodysplastic syndromes/myeloproliferative neoplasms (8%), and myeloma (4%).

Most patients (90%) received peripheral blood transplants, but 10% received bone marrow. Patients had matched unrelated donors (48%), matched related donors (44%), mismatched unrelated donors (6%), and mismatched related donors (2%).

Most patients (84%) had severe cGVHD, but 16% had moderate cGVHD. About half of patients (52%) had four or more organs involved, and 78% received three or more prior lines of systemic therapy for cGVHD. The median time from cGVHD onset to trial enrollment was 33.5 months.

“[I]t was an advanced population that was highly treatment experienced,” Dr. Pidala said.

Initially, patients received ixazomib at 4 mg on days 1, 8, and 15 of a 28-day cycle for up to six cycles. However, the protocol was amended to allow additional cycles for responders.

Fifty-two percent of patients (n = 26) completed at least six cycles of therapy. The remaining patients stopped treatment because of unresolved toxicity, treatment failure, withdrawal, noncompliance, and death.

“Seven patients, in total, did continue therapy beyond six cycles,” Dr. Pidala said. “Six of these had partial response at 6 months, and one had stable disease.”

The overall response rate at 6 months was 40%. All 20 responders had partial responses.

The 6-month treatment failure rate was significantly lower in this trial than in historical controls (Blood 2013 121:2340-6). The rates of treatment failure were 28% and 44%, respectively (P = .01).

Treatment failure was largely due to the need for additional treatment, Dr. Pidala noted. Relapse and nonrelapse mortality were “uncommon” in this trial.

The investigators did not find any patient, transplant, or cGVHD-related factors significantly associated with 6-month treatment failure.

The failure-free survival rate at 6 months was 72% in this trial and 56% in historical controls. The failure-free survival rate at 12 months was 57% and 45%, respectively.

Serious adverse events occurred in 38% of patients on this trial. Patients required ixazomib dose reductions due to thrombocytopenia, fatigue, diarrhea, and infection.

There were five deaths, and two of them were considered possibly related to ixazomib.

“This was driven by the proximity of the death events to the last dose of ixazomib, specifically, within 1 month,” Dr. Pidala said. “One of these death events was a case of respiratory failure. The other was a case of sudden, unexplained death.”

The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At the meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

Dr. Pidala reported having nothing to disclose. Other investigators reported relationships with Pfizer, CSL Behring, Agios, Incyte, Genentech, and Takeda. The trial was sponsored by the Fred Hutchinson Cancer Research Center in collaboration with the National Cancer Institute.

[email protected]

SOURCE: Pidala J et al. TCT 2019, Abstract 35.

HOUSTON – Ixazomib may reduce treatment failure in patients with advanced chronic graft-versus-host disease (cGVHD), findings from a phase 2 trial suggest.

Patients who received ixazomib in this trial had a lower rate of treatment failure – a composite endpoint of death, relapse, and need for additional systemic immunosuppressive therapy – than that of historical controls.

Joseph Pidala, MD, PhD, of Moffitt Cancer Center in Tampa, Fla., presented this finding at the Transplantation & Cellular Therapy Meetings.

The trial (NCT02513498) included 50 patients with a median age of 58 years (range, 44-65). Patients had acute leukemia (52%), lymphoma (18%), chronic leukemia (12%), myelodysplastic syndromes/myeloproliferative neoplasms (8%), and myeloma (4%).

Most patients (90%) received peripheral blood transplants, but 10% received bone marrow. Patients had matched unrelated donors (48%), matched related donors (44%), mismatched unrelated donors (6%), and mismatched related donors (2%).

Most patients (84%) had severe cGVHD, but 16% had moderate cGVHD. About half of patients (52%) had four or more organs involved, and 78% received three or more prior lines of systemic therapy for cGVHD. The median time from cGVHD onset to trial enrollment was 33.5 months.

“[I]t was an advanced population that was highly treatment experienced,” Dr. Pidala said.

Initially, patients received ixazomib at 4 mg on days 1, 8, and 15 of a 28-day cycle for up to six cycles. However, the protocol was amended to allow additional cycles for responders.

Fifty-two percent of patients (n = 26) completed at least six cycles of therapy. The remaining patients stopped treatment because of unresolved toxicity, treatment failure, withdrawal, noncompliance, and death.

“Seven patients, in total, did continue therapy beyond six cycles,” Dr. Pidala said. “Six of these had partial response at 6 months, and one had stable disease.”

The overall response rate at 6 months was 40%. All 20 responders had partial responses.

The 6-month treatment failure rate was significantly lower in this trial than in historical controls (Blood 2013 121:2340-6). The rates of treatment failure were 28% and 44%, respectively (P = .01).

Treatment failure was largely due to the need for additional treatment, Dr. Pidala noted. Relapse and nonrelapse mortality were “uncommon” in this trial.

The investigators did not find any patient, transplant, or cGVHD-related factors significantly associated with 6-month treatment failure.

The failure-free survival rate at 6 months was 72% in this trial and 56% in historical controls. The failure-free survival rate at 12 months was 57% and 45%, respectively.

Serious adverse events occurred in 38% of patients on this trial. Patients required ixazomib dose reductions due to thrombocytopenia, fatigue, diarrhea, and infection.

There were five deaths, and two of them were considered possibly related to ixazomib.

“This was driven by the proximity of the death events to the last dose of ixazomib, specifically, within 1 month,” Dr. Pidala said. “One of these death events was a case of respiratory failure. The other was a case of sudden, unexplained death.”

The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At the meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

Dr. Pidala reported having nothing to disclose. Other investigators reported relationships with Pfizer, CSL Behring, Agios, Incyte, Genentech, and Takeda. The trial was sponsored by the Fred Hutchinson Cancer Research Center in collaboration with the National Cancer Institute.

[email protected]

SOURCE: Pidala J et al. TCT 2019, Abstract 35.

HOUSTON – Ixazomib may reduce treatment failure in patients with advanced chronic graft-versus-host disease (cGVHD), findings from a phase 2 trial suggest.

Patients who received ixazomib in this trial had a lower rate of treatment failure – a composite endpoint of death, relapse, and need for additional systemic immunosuppressive therapy – than that of historical controls.

Joseph Pidala, MD, PhD, of Moffitt Cancer Center in Tampa, Fla., presented this finding at the Transplantation & Cellular Therapy Meetings.

The trial (NCT02513498) included 50 patients with a median age of 58 years (range, 44-65). Patients had acute leukemia (52%), lymphoma (18%), chronic leukemia (12%), myelodysplastic syndromes/myeloproliferative neoplasms (8%), and myeloma (4%).

Most patients (90%) received peripheral blood transplants, but 10% received bone marrow. Patients had matched unrelated donors (48%), matched related donors (44%), mismatched unrelated donors (6%), and mismatched related donors (2%).

Most patients (84%) had severe cGVHD, but 16% had moderate cGVHD. About half of patients (52%) had four or more organs involved, and 78% received three or more prior lines of systemic therapy for cGVHD. The median time from cGVHD onset to trial enrollment was 33.5 months.

“[I]t was an advanced population that was highly treatment experienced,” Dr. Pidala said.

Initially, patients received ixazomib at 4 mg on days 1, 8, and 15 of a 28-day cycle for up to six cycles. However, the protocol was amended to allow additional cycles for responders.

Fifty-two percent of patients (n = 26) completed at least six cycles of therapy. The remaining patients stopped treatment because of unresolved toxicity, treatment failure, withdrawal, noncompliance, and death.

“Seven patients, in total, did continue therapy beyond six cycles,” Dr. Pidala said. “Six of these had partial response at 6 months, and one had stable disease.”

The overall response rate at 6 months was 40%. All 20 responders had partial responses.

The 6-month treatment failure rate was significantly lower in this trial than in historical controls (Blood 2013 121:2340-6). The rates of treatment failure were 28% and 44%, respectively (P = .01).

Treatment failure was largely due to the need for additional treatment, Dr. Pidala noted. Relapse and nonrelapse mortality were “uncommon” in this trial.

The investigators did not find any patient, transplant, or cGVHD-related factors significantly associated with 6-month treatment failure.

The failure-free survival rate at 6 months was 72% in this trial and 56% in historical controls. The failure-free survival rate at 12 months was 57% and 45%, respectively.

Serious adverse events occurred in 38% of patients on this trial. Patients required ixazomib dose reductions due to thrombocytopenia, fatigue, diarrhea, and infection.

There were five deaths, and two of them were considered possibly related to ixazomib.

“This was driven by the proximity of the death events to the last dose of ixazomib, specifically, within 1 month,” Dr. Pidala said. “One of these death events was a case of respiratory failure. The other was a case of sudden, unexplained death.”

The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At the meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

Dr. Pidala reported having nothing to disclose. Other investigators reported relationships with Pfizer, CSL Behring, Agios, Incyte, Genentech, and Takeda. The trial was sponsored by the Fred Hutchinson Cancer Research Center in collaboration with the National Cancer Institute.

[email protected]

SOURCE: Pidala J et al. TCT 2019, Abstract 35.

The incidence of colorectal cancer in patients aged 20-49 years is increasing, but the diagnosis is often delayed in this age group because of a failure by both patients and physicians to recognize the symptoms as related to CRC, a survey suggests.

Of 1,195 colorectal cancer (CRC) patients or survivors aged under 50 years who responded to the web-based survey, 63% waited between 3 and 12 months before visiting their doctor after experiencing symptoms, including bloating, constipation, rectal bleeding, blood in stool, abdominal pain, flatulence, fatigue, or nausea and vomiting, Ronit I. Yarden, PhD, reported during a press conference highlighting data to be presented at the upcoming American Association for Cancer Research (AACR) annual meeting in Atlanta.

More than half of the respondents (56%) had at least three symptoms and still waited at least 3 months before visiting a doctor.

“And almost one in four waited at least a year to visit their doctor or other provider,” said Dr. Yarden, director of medical affairs for the Colorectal Cancer Alliance in Washington, D.C., which conducted the survey.

When patients did seek medical care, they often were initially misdiagnosed. In fact, 67% of the respondents reported having seen at least two physicians, with some seeing more than four physicians, before being diagnosed correctly with CRC, she said, noting that among the most common misdiagnoses were hemorrhoids and inflammatory bowel disease.


The delays in treatment and correct diagnoses have life-threatening implications; data show that, while the overall incidence of CRC is declining, the incidence in younger adults has increased. According to the American Cancer Society, most CRC patients over the age of 50 years are diagnosed in the early stages of disease, whereas 71% of the young-onset survey respondents were diagnosed at stage III or IV, Dr. Yarden said.

This is important, because 5-year survival is only 70% for stage III disease, and is less than 50% for stage IV disease. One in four survey respondents was diagnosed at stage IV, she said.

The survey included young-onset patients and survivors and was administered over social media to track the self-reported clinical, psychosocial, financial, and quality of life experiences of “this often-overlooked group,” she said.

The majority of participants (57%) were diagnosed between the ages of 40 and 49 years, a third were diagnosed between the ages of 30 and 39, and about 10% were diagnosed before the age of 30.

The findings underscore the need for greater awareness that “colorectal cancer, which is one of the most preventable diseases, can happen in younger adults,” Dr. Yarden said, also noting that extended screening is needed “if we want to beat this disease.”

John D. Carpten, PhD, the AACR meeting program chair and press conference comoderator, agreed that the findings could have significant policy implications, as many screening recommendations for CRC call for screening beginning at age 50 years.

“So for those individuals who are diagnosed with colon cancer in their 30s or 40s, this raises a potentially significant problem,” he said. “Additional studies need to be done to actually identify the factors influencing these early onset cancers. ... Hopefully that will improve our ability to detect these cancers earlier and to identify the most appropriate and effective ways to treat these cancers – particularly given that they tend to be diagnosed at more advanced stages.”

Work is also needed to help ensure access to the most appropriate care for younger patients – a concern related to disparities in health care access, he said, noting that the AACR meeting with “have a strong emphasis on disparities.”

Disparities can be related to race/ethnicity, rural versus urban setting, and socioeconomic factors, but they can also be related to age – which might be a particular problem in the case of early-onset CRC, he said.

Adolescent and young adult patients, in particular, represent “sort of a new disparity group,” and “can sometimes get lost in the system,” said Dr. Carpten, professor and chair of translational genomics and director of the Institute of Translational Genomics at the University of Southern California, Los Angeles.

“So we need to find better ways to detect these cancers earlier so we can manage these better,” he said.

This study was funded by the Colorectal Cancer Alliance. Dr. Yarden reported having no conflicts of interest.

SOURCE: Yarden R et al. AACR 2019, Abstract preview.

The incidence of colorectal cancer in patients aged 20-49 years is increasing, but the diagnosis is often delayed in this age group because of a failure by both patients and physicians to recognize the symptoms as related to CRC, a survey suggests.

Of 1,195 colorectal cancer (CRC) patients or survivors aged under 50 years who responded to the web-based survey, 63% waited between 3 and 12 months before visiting their doctor after experiencing symptoms, including bloating, constipation, rectal bleeding, blood in stool, abdominal pain, flatulence, fatigue, or nausea and vomiting, Ronit I. Yarden, PhD, reported during a press conference highlighting data to be presented at the upcoming American Association for Cancer Research (AACR) annual meeting in Atlanta.

More than half of the respondents (56%) had at least three symptoms and still waited at least 3 months before visiting a doctor.

“And almost one in four waited at least a year to visit their doctor or other provider,” said Dr. Yarden, director of medical affairs for the Colorectal Cancer Alliance in Washington, D.C., which conducted the survey.

When patients did seek medical care, they often were initially misdiagnosed. In fact, 67% of the respondents reported having seen at least two physicians, with some seeing more than four physicians, before being diagnosed correctly with CRC, she said, noting that among the most common misdiagnoses were hemorrhoids and inflammatory bowel disease.


The delays in treatment and correct diagnoses have life-threatening implications; data show that, while the overall incidence of CRC is declining, the incidence in younger adults has increased. According to the American Cancer Society, most CRC patients over the age of 50 years are diagnosed in the early stages of disease, whereas 71% of the young-onset survey respondents were diagnosed at stage III or IV, Dr. Yarden said.

This is important, because 5-year survival is only 70% for stage III disease, and is less than 50% for stage IV disease. One in four survey respondents was diagnosed at stage IV, she said.

The survey included young-onset patients and survivors and was administered over social media to track the self-reported clinical, psychosocial, financial, and quality of life experiences of “this often-overlooked group,” she said.

The majority of participants (57%) were diagnosed between the ages of 40 and 49 years, a third were diagnosed between the ages of 30 and 39, and about 10% were diagnosed before the age of 30.

The findings underscore the need for greater awareness that “colorectal cancer, which is one of the most preventable diseases, can happen in younger adults,” Dr. Yarden said, also noting that extended screening is needed “if we want to beat this disease.”

John D. Carpten, PhD, the AACR meeting program chair and press conference comoderator, agreed that the findings could have significant policy implications, as many screening recommendations for CRC call for screening beginning at age 50 years.

“So for those individuals who are diagnosed with colon cancer in their 30s or 40s, this raises a potentially significant problem,” he said. “Additional studies need to be done to actually identify the factors influencing these early onset cancers. ... Hopefully that will improve our ability to detect these cancers earlier and to identify the most appropriate and effective ways to treat these cancers – particularly given that they tend to be diagnosed at more advanced stages.”

Work is also needed to help ensure access to the most appropriate care for younger patients – a concern related to disparities in health care access, he said, noting that the AACR meeting with “have a strong emphasis on disparities.”

Disparities can be related to race/ethnicity, rural versus urban setting, and socioeconomic factors, but they can also be related to age – which might be a particular problem in the case of early-onset CRC, he said.

Adolescent and young adult patients, in particular, represent “sort of a new disparity group,” and “can sometimes get lost in the system,” said Dr. Carpten, professor and chair of translational genomics and director of the Institute of Translational Genomics at the University of Southern California, Los Angeles.

“So we need to find better ways to detect these cancers earlier so we can manage these better,” he said.

This study was funded by the Colorectal Cancer Alliance. Dr. Yarden reported having no conflicts of interest.

SOURCE: Yarden R et al. AACR 2019, Abstract preview.

The incidence of colorectal cancer in patients aged 20-49 years is increasing, but the diagnosis is often delayed in this age group because of a failure by both patients and physicians to recognize the symptoms as related to CRC, a survey suggests.

Of 1,195 colorectal cancer (CRC) patients or survivors aged under 50 years who responded to the web-based survey, 63% waited between 3 and 12 months before visiting their doctor after experiencing symptoms, including bloating, constipation, rectal bleeding, blood in stool, abdominal pain, flatulence, fatigue, or nausea and vomiting, Ronit I. Yarden, PhD, reported during a press conference highlighting data to be presented at the upcoming American Association for Cancer Research (AACR) annual meeting in Atlanta.

More than half of the respondents (56%) had at least three symptoms and still waited at least 3 months before visiting a doctor.

“And almost one in four waited at least a year to visit their doctor or other provider,” said Dr. Yarden, director of medical affairs for the Colorectal Cancer Alliance in Washington, D.C., which conducted the survey.

When patients did seek medical care, they often were initially misdiagnosed. In fact, 67% of the respondents reported having seen at least two physicians, with some seeing more than four physicians, before being diagnosed correctly with CRC, she said, noting that among the most common misdiagnoses were hemorrhoids and inflammatory bowel disease.


The delays in treatment and correct diagnoses have life-threatening implications; data show that, while the overall incidence of CRC is declining, the incidence in younger adults has increased. According to the American Cancer Society, most CRC patients over the age of 50 years are diagnosed in the early stages of disease, whereas 71% of the young-onset survey respondents were diagnosed at stage III or IV, Dr. Yarden said.

This is important, because 5-year survival is only 70% for stage III disease, and is less than 50% for stage IV disease. One in four survey respondents was diagnosed at stage IV, she said.

The survey included young-onset patients and survivors and was administered over social media to track the self-reported clinical, psychosocial, financial, and quality of life experiences of “this often-overlooked group,” she said.

The majority of participants (57%) were diagnosed between the ages of 40 and 49 years, a third were diagnosed between the ages of 30 and 39, and about 10% were diagnosed before the age of 30.

The findings underscore the need for greater awareness that “colorectal cancer, which is one of the most preventable diseases, can happen in younger adults,” Dr. Yarden said, also noting that extended screening is needed “if we want to beat this disease.”

John D. Carpten, PhD, the AACR meeting program chair and press conference comoderator, agreed that the findings could have significant policy implications, as many screening recommendations for CRC call for screening beginning at age 50 years.

“So for those individuals who are diagnosed with colon cancer in their 30s or 40s, this raises a potentially significant problem,” he said. “Additional studies need to be done to actually identify the factors influencing these early onset cancers. ... Hopefully that will improve our ability to detect these cancers earlier and to identify the most appropriate and effective ways to treat these cancers – particularly given that they tend to be diagnosed at more advanced stages.”

Work is also needed to help ensure access to the most appropriate care for younger patients – a concern related to disparities in health care access, he said, noting that the AACR meeting with “have a strong emphasis on disparities.”

Disparities can be related to race/ethnicity, rural versus urban setting, and socioeconomic factors, but they can also be related to age – which might be a particular problem in the case of early-onset CRC, he said.

Adolescent and young adult patients, in particular, represent “sort of a new disparity group,” and “can sometimes get lost in the system,” said Dr. Carpten, professor and chair of translational genomics and director of the Institute of Translational Genomics at the University of Southern California, Los Angeles.

“So we need to find better ways to detect these cancers earlier so we can manage these better,” he said.

This study was funded by the Colorectal Cancer Alliance. Dr. Yarden reported having no conflicts of interest.

SOURCE: Yarden R et al. AACR 2019, Abstract preview.

SAN DIEGO – In the pediatric intensive care unit (PICU), rapid whole genome sequencing (rWGS) with targeted phenotype analysis often leads to specific changes in patient management, similar to what is seen when rWGS is applied to neonatal ICUs. The findings come from the first study to look at outcomes of rWGS in the PICU outside of infancy.

NaiyanaDonraman/Thinkstock

In the NICU, previous studies have shown an rWGS diagnostic rate ranging from 36% to 57%, and an estimated 49%-72% of these diagnoses result in changes to patient management; 38%-45% of those diagnoses had not been previously considered.

The researchers found similar benefits when the age of patients was extended to 18 years in the PICU. “We were happy to see we were able to make specific changes in ICU management, with three of those being medication changes based on the diagnosis, and one being in the transition to palliative care while the patient was still in the PICU,” Erica Sanford, MD, said in an interview.

Dr. Sanford is a pediatric clinical care fellow at the University of California, San Diego. She presented the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Changes as a result of rWGS included factor replacement for a factor XIII deficiency, avoidance of renal biopsy because the diagnosis was made genetically, and use of serial MRI and other imaging methods to identify disorder-related sequela. “We’re hopeful as the turnaround for genome sequencing decreases that we’ll be able to offer this as a test when appropriate when a patient is presenting with an illness that doesn’t have a clear etiologic diagnosis,” said Dr. Sanford.

Certainly not every patient in the PICU should undergo rWGS, given its expense. Although the study was too small to identify candidate patients, there were some trends – patients in cardiac arrest were more likely to be receiving a genetic diagnosis. “We weren’t able to answer the question of which patients in the pediatric ICU should get whole genome sequencing – our next step is to have a larger group of patients so we can determine specifically which patients might benefit,” said Dr. Sanford. The team also plans to do a cost analysis of rWGS in the PICU setting.

The researchers examined data from a PICU at a tertiary children’s hospital, including records from 38 patients who underwent rWGS between July 2016 and May 2018. Based on the initial sequencing results, 18 underwent diagnostic rWGS. The average age of children was 5.7 years (median 3 years), with patients ranging from 4 months to 18 years old.

The most common reasons for PICU admission were shock (16% of all patients, 17% of patients who received diagnostic rWGS), respiratory failure (18% and 17%), cardiac arrest (13% and 22%), and altered mental status (13% and 11%).

Eleven of 18 patients (61%) who received an rWGS diagnosis experienced a subacute, non-ICU change in management. Four diagnoses (22%) led to a change in ICU management, and three led to no changes in patient management.

The National Institutes of Health funded the study. Dr. Sanford had no relevant financial disclosures.

SOURCE: Sanford E et al. CCC48, Abstract 373.

SAN DIEGO – In the pediatric intensive care unit (PICU), rapid whole genome sequencing (rWGS) with targeted phenotype analysis often leads to specific changes in patient management, similar to what is seen when rWGS is applied to neonatal ICUs. The findings come from the first study to look at outcomes of rWGS in the PICU outside of infancy.

NaiyanaDonraman/Thinkstock

In the NICU, previous studies have shown an rWGS diagnostic rate ranging from 36% to 57%, and an estimated 49%-72% of these diagnoses result in changes to patient management; 38%-45% of those diagnoses had not been previously considered.

The researchers found similar benefits when the age of patients was extended to 18 years in the PICU. “We were happy to see we were able to make specific changes in ICU management, with three of those being medication changes based on the diagnosis, and one being in the transition to palliative care while the patient was still in the PICU,” Erica Sanford, MD, said in an interview.

Dr. Sanford is a pediatric clinical care fellow at the University of California, San Diego. She presented the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Changes as a result of rWGS included factor replacement for a factor XIII deficiency, avoidance of renal biopsy because the diagnosis was made genetically, and use of serial MRI and other imaging methods to identify disorder-related sequela. “We’re hopeful as the turnaround for genome sequencing decreases that we’ll be able to offer this as a test when appropriate when a patient is presenting with an illness that doesn’t have a clear etiologic diagnosis,” said Dr. Sanford.

Certainly not every patient in the PICU should undergo rWGS, given its expense. Although the study was too small to identify candidate patients, there were some trends – patients in cardiac arrest were more likely to be receiving a genetic diagnosis. “We weren’t able to answer the question of which patients in the pediatric ICU should get whole genome sequencing – our next step is to have a larger group of patients so we can determine specifically which patients might benefit,” said Dr. Sanford. The team also plans to do a cost analysis of rWGS in the PICU setting.

The researchers examined data from a PICU at a tertiary children’s hospital, including records from 38 patients who underwent rWGS between July 2016 and May 2018. Based on the initial sequencing results, 18 underwent diagnostic rWGS. The average age of children was 5.7 years (median 3 years), with patients ranging from 4 months to 18 years old.

The most common reasons for PICU admission were shock (16% of all patients, 17% of patients who received diagnostic rWGS), respiratory failure (18% and 17%), cardiac arrest (13% and 22%), and altered mental status (13% and 11%).

Eleven of 18 patients (61%) who received an rWGS diagnosis experienced a subacute, non-ICU change in management. Four diagnoses (22%) led to a change in ICU management, and three led to no changes in patient management.

The National Institutes of Health funded the study. Dr. Sanford had no relevant financial disclosures.

SOURCE: Sanford E et al. CCC48, Abstract 373.

SAN DIEGO – In the pediatric intensive care unit (PICU), rapid whole genome sequencing (rWGS) with targeted phenotype analysis often leads to specific changes in patient management, similar to what is seen when rWGS is applied to neonatal ICUs. The findings come from the first study to look at outcomes of rWGS in the PICU outside of infancy.

NaiyanaDonraman/Thinkstock

In the NICU, previous studies have shown an rWGS diagnostic rate ranging from 36% to 57%, and an estimated 49%-72% of these diagnoses result in changes to patient management; 38%-45% of those diagnoses had not been previously considered.

The researchers found similar benefits when the age of patients was extended to 18 years in the PICU. “We were happy to see we were able to make specific changes in ICU management, with three of those being medication changes based on the diagnosis, and one being in the transition to palliative care while the patient was still in the PICU,” Erica Sanford, MD, said in an interview.

Dr. Sanford is a pediatric clinical care fellow at the University of California, San Diego. She presented the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Changes as a result of rWGS included factor replacement for a factor XIII deficiency, avoidance of renal biopsy because the diagnosis was made genetically, and use of serial MRI and other imaging methods to identify disorder-related sequela. “We’re hopeful as the turnaround for genome sequencing decreases that we’ll be able to offer this as a test when appropriate when a patient is presenting with an illness that doesn’t have a clear etiologic diagnosis,” said Dr. Sanford.

Certainly not every patient in the PICU should undergo rWGS, given its expense. Although the study was too small to identify candidate patients, there were some trends – patients in cardiac arrest were more likely to be receiving a genetic diagnosis. “We weren’t able to answer the question of which patients in the pediatric ICU should get whole genome sequencing – our next step is to have a larger group of patients so we can determine specifically which patients might benefit,” said Dr. Sanford. The team also plans to do a cost analysis of rWGS in the PICU setting.

The researchers examined data from a PICU at a tertiary children’s hospital, including records from 38 patients who underwent rWGS between July 2016 and May 2018. Based on the initial sequencing results, 18 underwent diagnostic rWGS. The average age of children was 5.7 years (median 3 years), with patients ranging from 4 months to 18 years old.

The most common reasons for PICU admission were shock (16% of all patients, 17% of patients who received diagnostic rWGS), respiratory failure (18% and 17%), cardiac arrest (13% and 22%), and altered mental status (13% and 11%).

Eleven of 18 patients (61%) who received an rWGS diagnosis experienced a subacute, non-ICU change in management. Four diagnoses (22%) led to a change in ICU management, and three led to no changes in patient management.

The National Institutes of Health funded the study. Dr. Sanford had no relevant financial disclosures.

SOURCE: Sanford E et al. CCC48, Abstract 373.

Case Report

A 60-year-old Cambodian woman presented with recurrent fever (temperature, up to 38.8°C) 7 months after receiving a kidney transplant secondary to polycystic kidney disease. Fever was attributed to recurrent pyelonephritis of the native kidneys while on mycophenolate mofetil, tacrolimus, and prednisone. As a result, she underwent a bilateral native nephrectomy and was found to have peritoneal nodules. Pathology of both native kidneys and peritoneal tissue revealed caseating granulomas and acid-fast bacilli (AFB) diagnostic for kidney and peritoneal tuberculosis (TB). She had no history of TB, and a TB skin test (purified protein derivative [PPD]) upon entering the United States from Cambodia a decade earlier was negative. Additionally, her pretransplantation PPD was negative.

Treatment with isoniazid, ethambutol, pyrazinamide, and levofloxacin was initiated immediately upon diagnosis, and all of her immunosuppressive medications—mycophenolate mofetil, tacrolimus, and prednisone—were discontinued. Her symptoms subsided within 1 week, and she was discharged from the hospital. Over the next 2 months, her immunosuppressive medications were restarted, and her TB medications were periodically discontinued by the Tuberculosis Control Program at the Department of Health (Philadelphia, Pennsylvania) due to severe thrombocytopenia. During this time, she was closely monitored twice weekly in the clinic with blood draws performed weekly.

Approximately 10 weeks after initiation of treatment, she noted recurrent subjective fever (temperature, up to 38.8°C) and painful lesions on the right side of the flank, left breast, and left arm of 3 days’ duration. Physical examination revealed a warm, dull red, tender nodule on the right side of the flank (Figure 1) and subcutaneous nodules with no overlying skin changes on the left breast and left arm. A biopsy of the lesion on the right side of the flank was performed, which resulted in substantial purulent drainage. Histologic analysis showed an inflammatory infiltrate within the deep dermis composed of neutrophils, macrophages, and giant cells, indicative of suppurative granulomatous dermatitis (Figure 2). Ziehl-Neelsen stain demonstrated rare AFB within the cytoplasm of macrophages, suggestive of Mycobacterium tuberculosis infection (Figure 3). A repeat chest radiograph was normal.

Comment

Clinical Presentation
Cutaneous TB is an uncommon manifestation of TB that can occur either exogenously or endogenously.¹ It tends to occur primarily in previously infected TB patients through hematogenous, lymphatic, or contiguous spread.² Due to their immunocompromised state, solid organ transplant recipients have an increased incidence of primary and reactivated latent TB reported to be 20 to 74 times greater than the general population.^3,4 One report stated the total incidence of posttransplant TB as 0.48% in the West and 11.8% in endemic regions such as India.⁵ The occurrence of cutaneous TB is rare among solid organ transplant recipients.¹ On average, a diagnosis of latent TB is made 9 months after transplantation because of the opportunistic nature of M tuberculosis in an immunosuppressed environment.⁶

TB Subtypes
Cutaneous TB can be in the form of localized disease (eg, primary tuberculous chancre, TB verrucosa cutis, lupus vulgaris, smear-negative scrofuloderma), disseminated disease (eg, disseminated TB, TB gumma, orificial TB, miliary cutaneous TB), or tuberculids (eg, papulonecrotic tuberculid, lichen scrofulosorum, erythema induratum).⁷ Due to the pustular epithelioid cell granulomas and AFB positivity of the involved cutaneous lesions, our patient’s TB can be classified as a metastatic TB abscess or gummatous TB.⁷

Metastatic TB abscess, an uncommon subtype of cutaneous TB, generally is only seen in malnourished children and notably immunocompromised individuals.^2,8,9 In these individuals, systemic failure of cell-mediated immunity enables M tuberculosis to hematogenously infect various organs of the body, resulting in alternative forms of TB, such as gummatous-type TB.¹⁰ One study reported that of the 0.1% of dermatology patients presenting with cutaneous TB, only 5.4% of these individuals had the rarer gummatous form.⁷ These metastatic TB abscesses begin as a single or multiple nontender subcutaneous nodule(s), which breaks down and softens to form a draining sinus abscess.^2,8,9 Abscesses are most commonly seen on the trunk and extremities; however, they can be found nearly anywhere on the body.⁸ The pathology of cutaneous TB lesions demonstrates caseating necrosis with epithelioid and giant cells forming a surrounding rim.⁹

Diagnosis
Diagnosis may be difficult because of the vast number of dermatologic conditions that resemble cutaneous TB, including mycoses, sarcoidosis, leishmaniasis, leprosy, syphilis, other non-TB mycobacteria, and Wegener granulomatosis.⁹ Thus, confirmatory diagnosis is made via clinical presentation, detailed history and physical examination, and laboratory tests.¹¹ These tests include the Mantoux tuberculin skin test (PPD or TST) or IFN-γ release assays (QuantiFERON-TB Gold test), identification of AFB on skin biopsy, and isolation of M tuberculosis from tissue culture or polymerase chain reaction.¹¹Given our patient’s history, clinical presentation, and the identification of mycobacteria with AFB stain, the diagnosis of cutaneous gummatous TB was confirmed.

At-Risk Populations
The recommendation for the identification of at-risk populations for latent TB testing and treatment have been clearly defined by the World Health Organization (Table).¹² Our patient met 2 of these criteria: she had been preparing for organ transplantation and was from a country with high TB burden. Such at-risk patients should be tested for a latent TB infection with either IFN-γ release assays or PPD.¹²These recommendations are supported by the American Thoracic Society, which specifies that a positive PPD test in a solid organ transplant recipient is defined as having induration greater than 5 mm.¹³ However, even with a high index of suspicion, it has been reported that as many as 75% to 80% of organ recipients who developed TB had a false-negative pretransplantation PPD due to anergy from immunosuppression.¹⁴ Given the notable risk for TB in organ transplant recipients on immunosuppressive medications, these patients should receive screening tests with high sensitivity and specificity, while controlling for possible anergy. Unfortunately, the role of anergy testing in the diagnosis of latent TB is not well defined, and thus not recommended at this time.^13,15 It is recommended to repeat PPD testing 7 to 10 days after the first test as a booster effect to rule out false-negative results.¹⁵

Finally, thrombocytopenia is an infrequent, life-threatening complication that can be acquired by immunocompromised patients on anti-TB therapy.¹⁷ Drug-induced thrombocytopenia can be caused by a variety of medications, including rifampicin, isoniazid, ethambutol, and pyrazinamide. Diagnosis of drug-induced thrombocytopenia can be confirmed only after discontinuation of the suspected drug and subsequent resolution of the thrombocytopenia.¹⁷ Our patient initially became thrombocytopenic while taking isoniazid, ethambutol, pyrazinamide, and levofloxacin. However, her platelet levels improved once the pyrazinamide was discontinued, thereby suggesting pyrazinamide-induced thrombocytopenia.

Conclusion

The risk for infectious disease reactivation in an immunocompromised patient undergoing transplant surgery is notable. Our findings emphasize the value of a comprehensive pretransplant evaluation, vigilance even when test results appear negative, and treatment of latent TB within this population.^16,18,19 Furthermore, this case illustrates a noteworthy example of a rare form of cutaneous TB, which should be considered and included in the differential for cutaneous lesions in an immunosuppressed patient.

Case Report

A 60-year-old Cambodian woman presented with recurrent fever (temperature, up to 38.8°C) 7 months after receiving a kidney transplant secondary to polycystic kidney disease. Fever was attributed to recurrent pyelonephritis of the native kidneys while on mycophenolate mofetil, tacrolimus, and prednisone. As a result, she underwent a bilateral native nephrectomy and was found to have peritoneal nodules. Pathology of both native kidneys and peritoneal tissue revealed caseating granulomas and acid-fast bacilli (AFB) diagnostic for kidney and peritoneal tuberculosis (TB). She had no history of TB, and a TB skin test (purified protein derivative [PPD]) upon entering the United States from Cambodia a decade earlier was negative. Additionally, her pretransplantation PPD was negative.

Treatment with isoniazid, ethambutol, pyrazinamide, and levofloxacin was initiated immediately upon diagnosis, and all of her immunosuppressive medications—mycophenolate mofetil, tacrolimus, and prednisone—were discontinued. Her symptoms subsided within 1 week, and she was discharged from the hospital. Over the next 2 months, her immunosuppressive medications were restarted, and her TB medications were periodically discontinued by the Tuberculosis Control Program at the Department of Health (Philadelphia, Pennsylvania) due to severe thrombocytopenia. During this time, she was closely monitored twice weekly in the clinic with blood draws performed weekly.

Approximately 10 weeks after initiation of treatment, she noted recurrent subjective fever (temperature, up to 38.8°C) and painful lesions on the right side of the flank, left breast, and left arm of 3 days’ duration. Physical examination revealed a warm, dull red, tender nodule on the right side of the flank (Figure 1) and subcutaneous nodules with no overlying skin changes on the left breast and left arm. A biopsy of the lesion on the right side of the flank was performed, which resulted in substantial purulent drainage. Histologic analysis showed an inflammatory infiltrate within the deep dermis composed of neutrophils, macrophages, and giant cells, indicative of suppurative granulomatous dermatitis (Figure 2). Ziehl-Neelsen stain demonstrated rare AFB within the cytoplasm of macrophages, suggestive of Mycobacterium tuberculosis infection (Figure 3). A repeat chest radiograph was normal.

Comment

Clinical Presentation
Cutaneous TB is an uncommon manifestation of TB that can occur either exogenously or endogenously.¹ It tends to occur primarily in previously infected TB patients through hematogenous, lymphatic, or contiguous spread.² Due to their immunocompromised state, solid organ transplant recipients have an increased incidence of primary and reactivated latent TB reported to be 20 to 74 times greater than the general population.^3,4 One report stated the total incidence of posttransplant TB as 0.48% in the West and 11.8% in endemic regions such as India.⁵ The occurrence of cutaneous TB is rare among solid organ transplant recipients.¹ On average, a diagnosis of latent TB is made 9 months after transplantation because of the opportunistic nature of M tuberculosis in an immunosuppressed environment.⁶

TB Subtypes
Cutaneous TB can be in the form of localized disease (eg, primary tuberculous chancre, TB verrucosa cutis, lupus vulgaris, smear-negative scrofuloderma), disseminated disease (eg, disseminated TB, TB gumma, orificial TB, miliary cutaneous TB), or tuberculids (eg, papulonecrotic tuberculid, lichen scrofulosorum, erythema induratum).⁷ Due to the pustular epithelioid cell granulomas and AFB positivity of the involved cutaneous lesions, our patient’s TB can be classified as a metastatic TB abscess or gummatous TB.⁷

Metastatic TB abscess, an uncommon subtype of cutaneous TB, generally is only seen in malnourished children and notably immunocompromised individuals.^2,8,9 In these individuals, systemic failure of cell-mediated immunity enables M tuberculosis to hematogenously infect various organs of the body, resulting in alternative forms of TB, such as gummatous-type TB.¹⁰ One study reported that of the 0.1% of dermatology patients presenting with cutaneous TB, only 5.4% of these individuals had the rarer gummatous form.⁷ These metastatic TB abscesses begin as a single or multiple nontender subcutaneous nodule(s), which breaks down and softens to form a draining sinus abscess.^2,8,9 Abscesses are most commonly seen on the trunk and extremities; however, they can be found nearly anywhere on the body.⁸ The pathology of cutaneous TB lesions demonstrates caseating necrosis with epithelioid and giant cells forming a surrounding rim.⁹

Diagnosis
Diagnosis may be difficult because of the vast number of dermatologic conditions that resemble cutaneous TB, including mycoses, sarcoidosis, leishmaniasis, leprosy, syphilis, other non-TB mycobacteria, and Wegener granulomatosis.⁹ Thus, confirmatory diagnosis is made via clinical presentation, detailed history and physical examination, and laboratory tests.¹¹ These tests include the Mantoux tuberculin skin test (PPD or TST) or IFN-γ release assays (QuantiFERON-TB Gold test), identification of AFB on skin biopsy, and isolation of M tuberculosis from tissue culture or polymerase chain reaction.¹¹Given our patient’s history, clinical presentation, and the identification of mycobacteria with AFB stain, the diagnosis of cutaneous gummatous TB was confirmed.

At-Risk Populations
The recommendation for the identification of at-risk populations for latent TB testing and treatment have been clearly defined by the World Health Organization (Table).¹² Our patient met 2 of these criteria: she had been preparing for organ transplantation and was from a country with high TB burden. Such at-risk patients should be tested for a latent TB infection with either IFN-γ release assays or PPD.¹²These recommendations are supported by the American Thoracic Society, which specifies that a positive PPD test in a solid organ transplant recipient is defined as having induration greater than 5 mm.¹³ However, even with a high index of suspicion, it has been reported that as many as 75% to 80% of organ recipients who developed TB had a false-negative pretransplantation PPD due to anergy from immunosuppression.¹⁴ Given the notable risk for TB in organ transplant recipients on immunosuppressive medications, these patients should receive screening tests with high sensitivity and specificity, while controlling for possible anergy. Unfortunately, the role of anergy testing in the diagnosis of latent TB is not well defined, and thus not recommended at this time.^13,15 It is recommended to repeat PPD testing 7 to 10 days after the first test as a booster effect to rule out false-negative results.¹⁵

Finally, thrombocytopenia is an infrequent, life-threatening complication that can be acquired by immunocompromised patients on anti-TB therapy.¹⁷ Drug-induced thrombocytopenia can be caused by a variety of medications, including rifampicin, isoniazid, ethambutol, and pyrazinamide. Diagnosis of drug-induced thrombocytopenia can be confirmed only after discontinuation of the suspected drug and subsequent resolution of the thrombocytopenia.¹⁷ Our patient initially became thrombocytopenic while taking isoniazid, ethambutol, pyrazinamide, and levofloxacin. However, her platelet levels improved once the pyrazinamide was discontinued, thereby suggesting pyrazinamide-induced thrombocytopenia.

Conclusion

The risk for infectious disease reactivation in an immunocompromised patient undergoing transplant surgery is notable. Our findings emphasize the value of a comprehensive pretransplant evaluation, vigilance even when test results appear negative, and treatment of latent TB within this population.^16,18,19 Furthermore, this case illustrates a noteworthy example of a rare form of cutaneous TB, which should be considered and included in the differential for cutaneous lesions in an immunosuppressed patient.

Case Report

A 60-year-old Cambodian woman presented with recurrent fever (temperature, up to 38.8°C) 7 months after receiving a kidney transplant secondary to polycystic kidney disease. Fever was attributed to recurrent pyelonephritis of the native kidneys while on mycophenolate mofetil, tacrolimus, and prednisone. As a result, she underwent a bilateral native nephrectomy and was found to have peritoneal nodules. Pathology of both native kidneys and peritoneal tissue revealed caseating granulomas and acid-fast bacilli (AFB) diagnostic for kidney and peritoneal tuberculosis (TB). She had no history of TB, and a TB skin test (purified protein derivative [PPD]) upon entering the United States from Cambodia a decade earlier was negative. Additionally, her pretransplantation PPD was negative.

Treatment with isoniazid, ethambutol, pyrazinamide, and levofloxacin was initiated immediately upon diagnosis, and all of her immunosuppressive medications—mycophenolate mofetil, tacrolimus, and prednisone—were discontinued. Her symptoms subsided within 1 week, and she was discharged from the hospital. Over the next 2 months, her immunosuppressive medications were restarted, and her TB medications were periodically discontinued by the Tuberculosis Control Program at the Department of Health (Philadelphia, Pennsylvania) due to severe thrombocytopenia. During this time, she was closely monitored twice weekly in the clinic with blood draws performed weekly.

Approximately 10 weeks after initiation of treatment, she noted recurrent subjective fever (temperature, up to 38.8°C) and painful lesions on the right side of the flank, left breast, and left arm of 3 days’ duration. Physical examination revealed a warm, dull red, tender nodule on the right side of the flank (Figure 1) and subcutaneous nodules with no overlying skin changes on the left breast and left arm. A biopsy of the lesion on the right side of the flank was performed, which resulted in substantial purulent drainage. Histologic analysis showed an inflammatory infiltrate within the deep dermis composed of neutrophils, macrophages, and giant cells, indicative of suppurative granulomatous dermatitis (Figure 2). Ziehl-Neelsen stain demonstrated rare AFB within the cytoplasm of macrophages, suggestive of Mycobacterium tuberculosis infection (Figure 3). A repeat chest radiograph was normal.

Comment

Clinical Presentation
Cutaneous TB is an uncommon manifestation of TB that can occur either exogenously or endogenously.¹ It tends to occur primarily in previously infected TB patients through hematogenous, lymphatic, or contiguous spread.² Due to their immunocompromised state, solid organ transplant recipients have an increased incidence of primary and reactivated latent TB reported to be 20 to 74 times greater than the general population.^3,4 One report stated the total incidence of posttransplant TB as 0.48% in the West and 11.8% in endemic regions such as India.⁵ The occurrence of cutaneous TB is rare among solid organ transplant recipients.¹ On average, a diagnosis of latent TB is made 9 months after transplantation because of the opportunistic nature of M tuberculosis in an immunosuppressed environment.⁶

TB Subtypes
Cutaneous TB can be in the form of localized disease (eg, primary tuberculous chancre, TB verrucosa cutis, lupus vulgaris, smear-negative scrofuloderma), disseminated disease (eg, disseminated TB, TB gumma, orificial TB, miliary cutaneous TB), or tuberculids (eg, papulonecrotic tuberculid, lichen scrofulosorum, erythema induratum).⁷ Due to the pustular epithelioid cell granulomas and AFB positivity of the involved cutaneous lesions, our patient’s TB can be classified as a metastatic TB abscess or gummatous TB.⁷

Metastatic TB abscess, an uncommon subtype of cutaneous TB, generally is only seen in malnourished children and notably immunocompromised individuals.^2,8,9 In these individuals, systemic failure of cell-mediated immunity enables M tuberculosis to hematogenously infect various organs of the body, resulting in alternative forms of TB, such as gummatous-type TB.¹⁰ One study reported that of the 0.1% of dermatology patients presenting with cutaneous TB, only 5.4% of these individuals had the rarer gummatous form.⁷ These metastatic TB abscesses begin as a single or multiple nontender subcutaneous nodule(s), which breaks down and softens to form a draining sinus abscess.^2,8,9 Abscesses are most commonly seen on the trunk and extremities; however, they can be found nearly anywhere on the body.⁸ The pathology of cutaneous TB lesions demonstrates caseating necrosis with epithelioid and giant cells forming a surrounding rim.⁹

Diagnosis
Diagnosis may be difficult because of the vast number of dermatologic conditions that resemble cutaneous TB, including mycoses, sarcoidosis, leishmaniasis, leprosy, syphilis, other non-TB mycobacteria, and Wegener granulomatosis.⁹ Thus, confirmatory diagnosis is made via clinical presentation, detailed history and physical examination, and laboratory tests.¹¹ These tests include the Mantoux tuberculin skin test (PPD or TST) or IFN-γ release assays (QuantiFERON-TB Gold test), identification of AFB on skin biopsy, and isolation of M tuberculosis from tissue culture or polymerase chain reaction.¹¹Given our patient’s history, clinical presentation, and the identification of mycobacteria with AFB stain, the diagnosis of cutaneous gummatous TB was confirmed.

At-Risk Populations
The recommendation for the identification of at-risk populations for latent TB testing and treatment have been clearly defined by the World Health Organization (Table).¹² Our patient met 2 of these criteria: she had been preparing for organ transplantation and was from a country with high TB burden. Such at-risk patients should be tested for a latent TB infection with either IFN-γ release assays or PPD.¹²These recommendations are supported by the American Thoracic Society, which specifies that a positive PPD test in a solid organ transplant recipient is defined as having induration greater than 5 mm.¹³ However, even with a high index of suspicion, it has been reported that as many as 75% to 80% of organ recipients who developed TB had a false-negative pretransplantation PPD due to anergy from immunosuppression.¹⁴ Given the notable risk for TB in organ transplant recipients on immunosuppressive medications, these patients should receive screening tests with high sensitivity and specificity, while controlling for possible anergy. Unfortunately, the role of anergy testing in the diagnosis of latent TB is not well defined, and thus not recommended at this time.^13,15 It is recommended to repeat PPD testing 7 to 10 days after the first test as a booster effect to rule out false-negative results.¹⁵

Finally, thrombocytopenia is an infrequent, life-threatening complication that can be acquired by immunocompromised patients on anti-TB therapy.¹⁷ Drug-induced thrombocytopenia can be caused by a variety of medications, including rifampicin, isoniazid, ethambutol, and pyrazinamide. Diagnosis of drug-induced thrombocytopenia can be confirmed only after discontinuation of the suspected drug and subsequent resolution of the thrombocytopenia.¹⁷ Our patient initially became thrombocytopenic while taking isoniazid, ethambutol, pyrazinamide, and levofloxacin. However, her platelet levels improved once the pyrazinamide was discontinued, thereby suggesting pyrazinamide-induced thrombocytopenia.

Conclusion

The risk for infectious disease reactivation in an immunocompromised patient undergoing transplant surgery is notable. Our findings emphasize the value of a comprehensive pretransplant evaluation, vigilance even when test results appear negative, and treatment of latent TB within this population.^16,18,19 Furthermore, this case illustrates a noteworthy example of a rare form of cutaneous TB, which should be considered and included in the differential for cutaneous lesions in an immunosuppressed patient.

Sarcoidosis is a systemic noncaseating granuloma­tous disease of unknown etiology. The skin is the second most common location for disease mani­festation following the lungs.¹ Cutaneous sarcoidosis is present in 35% of patients with sarcoidosis and may be further subtyped by its morphologic characteristics (eg, hyperpigmented, papular, nodular, atrophic, ulcer­ative, psoriasiform). Cutaneous sarcoidosis has an increased tendency to occur at areas of prior injury such as surgeries or tattoos.² Although sarcoidosis affects all races and sexes, it is more prevalent in women and in the black population.³ 

The clinical presentation of sarcoidosis is difficult due to its morphologic variation, allowing for a wide differential diagnosis. With our patient’s presentation of atrophic plaques, the differential diagnosis included granuloma annulare, necrobiosis lipoidica, tumid lupus erythematosus, leprosy, and sarcoidosis; however, biopsy is required for definitive diagnosis. The characteristic histopathology for cutaneous sarcoidosis includes nonca­seating granulomas (Figure, A) composed of epithelioid histiocytes with giant cells surrounded by a lympho­cytic infiltrate. Noncaseating granulomas are consid­ered specific to sarcoidosis and are present in 71% to 89% of biopsied lesions.⁴ Interestingly, our patient pre­sented with a rare subtype of atrophic ulcerative cutane­ous sarcoidosis, necrobiosis lipoidica–like sarcoidosis, which is more common in females and in the black population. It is characterized by pink to violaceous plaques with depressed centers and prominent necrotiz­ing granuloma (Figure, B) on histopathology. In a small case series, all 3 patients with necrobiosis lipoidica–like sarcoidosis were female and had systemic involvement at the time of diagnosis.⁵ 

Sarcoidosis typically is a systemic disease with only a limited number of cases presenting with isolated cutane­ous findings. Therefore, patients require a systemic evalu­ation, which may include a chest radiograph, complete blood cell count, ophthalmologic examinations, thyroid testing, and vitamin D monitoring, as well as an echocar­diogram and electrocardiogram.² 

Treatment is guided by the severity of disease. For isolated cutaneous lesions, topical or intralesional high-potency steroids have been shown to be effective.^6,7 Several studies also have shown phototherapy and laser therapy as well as surgical excision to be beneficial.^8-10 Once cutaneous lesions become disfiguring or systemic involvement is found, systemic corticosteroids or other immunomodulatory medications may be warranted.¹¹ Our patient was started on intralesional and topical high-potency steroids, which failed, and she was transitioned to methotrexate and adalimumab. Unfortunately, even with advanced therapies, our patient did not have notableresolution of the lesions.

Sarcoidosis is a systemic noncaseating granuloma­tous disease of unknown etiology. The skin is the second most common location for disease mani­festation following the lungs.¹ Cutaneous sarcoidosis is present in 35% of patients with sarcoidosis and may be further subtyped by its morphologic characteristics (eg, hyperpigmented, papular, nodular, atrophic, ulcer­ative, psoriasiform). Cutaneous sarcoidosis has an increased tendency to occur at areas of prior injury such as surgeries or tattoos.² Although sarcoidosis affects all races and sexes, it is more prevalent in women and in the black population.³ 

The clinical presentation of sarcoidosis is difficult due to its morphologic variation, allowing for a wide differential diagnosis. With our patient’s presentation of atrophic plaques, the differential diagnosis included granuloma annulare, necrobiosis lipoidica, tumid lupus erythematosus, leprosy, and sarcoidosis; however, biopsy is required for definitive diagnosis. The characteristic histopathology for cutaneous sarcoidosis includes nonca­seating granulomas (Figure, A) composed of epithelioid histiocytes with giant cells surrounded by a lympho­cytic infiltrate. Noncaseating granulomas are consid­ered specific to sarcoidosis and are present in 71% to 89% of biopsied lesions.⁴ Interestingly, our patient pre­sented with a rare subtype of atrophic ulcerative cutane­ous sarcoidosis, necrobiosis lipoidica–like sarcoidosis, which is more common in females and in the black population. It is characterized by pink to violaceous plaques with depressed centers and prominent necrotiz­ing granuloma (Figure, B) on histopathology. In a small case series, all 3 patients with necrobiosis lipoidica–like sarcoidosis were female and had systemic involvement at the time of diagnosis.⁵ 

Sarcoidosis typically is a systemic disease with only a limited number of cases presenting with isolated cutane­ous findings. Therefore, patients require a systemic evalu­ation, which may include a chest radiograph, complete blood cell count, ophthalmologic examinations, thyroid testing, and vitamin D monitoring, as well as an echocar­diogram and electrocardiogram.² 

Treatment is guided by the severity of disease. For isolated cutaneous lesions, topical or intralesional high-potency steroids have been shown to be effective.^6,7 Several studies also have shown phototherapy and laser therapy as well as surgical excision to be beneficial.^8-10 Once cutaneous lesions become disfiguring or systemic involvement is found, systemic corticosteroids or other immunomodulatory medications may be warranted.¹¹ Our patient was started on intralesional and topical high-potency steroids, which failed, and she was transitioned to methotrexate and adalimumab. Unfortunately, even with advanced therapies, our patient did not have notableresolution of the lesions.

Sarcoidosis is a systemic noncaseating granuloma­tous disease of unknown etiology. The skin is the second most common location for disease mani­festation following the lungs.¹ Cutaneous sarcoidosis is present in 35% of patients with sarcoidosis and may be further subtyped by its morphologic characteristics (eg, hyperpigmented, papular, nodular, atrophic, ulcer­ative, psoriasiform). Cutaneous sarcoidosis has an increased tendency to occur at areas of prior injury such as surgeries or tattoos.² Although sarcoidosis affects all races and sexes, it is more prevalent in women and in the black population.³ 

The clinical presentation of sarcoidosis is difficult due to its morphologic variation, allowing for a wide differential diagnosis. With our patient’s presentation of atrophic plaques, the differential diagnosis included granuloma annulare, necrobiosis lipoidica, tumid lupus erythematosus, leprosy, and sarcoidosis; however, biopsy is required for definitive diagnosis. The characteristic histopathology for cutaneous sarcoidosis includes nonca­seating granulomas (Figure, A) composed of epithelioid histiocytes with giant cells surrounded by a lympho­cytic infiltrate. Noncaseating granulomas are consid­ered specific to sarcoidosis and are present in 71% to 89% of biopsied lesions.⁴ Interestingly, our patient pre­sented with a rare subtype of atrophic ulcerative cutane­ous sarcoidosis, necrobiosis lipoidica–like sarcoidosis, which is more common in females and in the black population. It is characterized by pink to violaceous plaques with depressed centers and prominent necrotiz­ing granuloma (Figure, B) on histopathology. In a small case series, all 3 patients with necrobiosis lipoidica–like sarcoidosis were female and had systemic involvement at the time of diagnosis.⁵ 

Sarcoidosis typically is a systemic disease with only a limited number of cases presenting with isolated cutane­ous findings. Therefore, patients require a systemic evalu­ation, which may include a chest radiograph, complete blood cell count, ophthalmologic examinations, thyroid testing, and vitamin D monitoring, as well as an echocar­diogram and electrocardiogram.² 

Treatment is guided by the severity of disease. For isolated cutaneous lesions, topical or intralesional high-potency steroids have been shown to be effective.^6,7 Several studies also have shown phototherapy and laser therapy as well as surgical excision to be beneficial.^8-10 Once cutaneous lesions become disfiguring or systemic involvement is found, systemic corticosteroids or other immunomodulatory medications may be warranted.¹¹ Our patient was started on intralesional and topical high-potency steroids, which failed, and she was transitioned to methotrexate and adalimumab. Unfortunately, even with advanced therapies, our patient did not have notableresolution of the lesions.

High expression of cyclin E1 (CCNE1) was associated with resistance to treatment with palbociclib plus fulvestrant in patients with hormone receptor–positive, metastatic breast cancer, according to a gene expression analysis.

Nicholas C. Turner, MD, PhD, of Royal Marsden Hospital and Institute of Cancer Research in London, and his colleagues used a gene expression panel to detect biomarkers related to the efficacy of palbociclib plus fulvestrant in patients with endocrine-pretreated metastatic breast cancer.

“No predictive biomarkers have been identified in randomized trials of CDK4/6 inhibitors,” the researchers wrote in the Journal of Clinical Oncology.

Study participants were randomly assigned to receive either combination palbociclib and fulvestrant (n = 194) or placebo and fulvestrant (n = 108). The primary analysis was completed using data from the PALOMA-3 trial, which included 10 genes selected from a panel search of 2,534 genes.

The association between level of gene expression and efficacy of palbociclib combination therapy was evaluated by way of advanced statistical analysis.

After analysis, the efficacy of palbociclib was found to be reduced with high levels of cyclin E1 mRNA expression compared with low levels (median PFS palbociclib arm, 7.6 vs. 14.1 months; placebo arm, 4.0 vs. 4.8 months; P = .00238).

“These data suggest that CCNE1 mRNA expression may be associated with the benefit from palbociclib in early-stage breast cancer,” they wrote.

The authors acknowledged that one key limitation of the study was that the biomarkers identified may not be relevant to other CDK4/6 inhibitor combinations.

“Additional methodologic and clinical validations are warranted to elucidate the role of CCNE1 mRNA expression as a biomarker of CDK4/6 inhibitor therapy,” they concluded.

The study was supported by Pfizer. The authors reported financial interests with AbbVie, AstraZeneca, Genentech, Novartis, Pfizer, and others.

SOURCE: Turner NC et al. J Clin Oncol. 2019 Feb 26. doi: 10.1200/JCO.18.00925.

High expression of cyclin E1 (CCNE1) was associated with resistance to treatment with palbociclib plus fulvestrant in patients with hormone receptor–positive, metastatic breast cancer, according to a gene expression analysis.

Nicholas C. Turner, MD, PhD, of Royal Marsden Hospital and Institute of Cancer Research in London, and his colleagues used a gene expression panel to detect biomarkers related to the efficacy of palbociclib plus fulvestrant in patients with endocrine-pretreated metastatic breast cancer.

“No predictive biomarkers have been identified in randomized trials of CDK4/6 inhibitors,” the researchers wrote in the Journal of Clinical Oncology.

Study participants were randomly assigned to receive either combination palbociclib and fulvestrant (n = 194) or placebo and fulvestrant (n = 108). The primary analysis was completed using data from the PALOMA-3 trial, which included 10 genes selected from a panel search of 2,534 genes.

The association between level of gene expression and efficacy of palbociclib combination therapy was evaluated by way of advanced statistical analysis.

After analysis, the efficacy of palbociclib was found to be reduced with high levels of cyclin E1 mRNA expression compared with low levels (median PFS palbociclib arm, 7.6 vs. 14.1 months; placebo arm, 4.0 vs. 4.8 months; P = .00238).

“These data suggest that CCNE1 mRNA expression may be associated with the benefit from palbociclib in early-stage breast cancer,” they wrote.

The authors acknowledged that one key limitation of the study was that the biomarkers identified may not be relevant to other CDK4/6 inhibitor combinations.

“Additional methodologic and clinical validations are warranted to elucidate the role of CCNE1 mRNA expression as a biomarker of CDK4/6 inhibitor therapy,” they concluded.

The study was supported by Pfizer. The authors reported financial interests with AbbVie, AstraZeneca, Genentech, Novartis, Pfizer, and others.

SOURCE: Turner NC et al. J Clin Oncol. 2019 Feb 26. doi: 10.1200/JCO.18.00925.

High expression of cyclin E1 (CCNE1) was associated with resistance to treatment with palbociclib plus fulvestrant in patients with hormone receptor–positive, metastatic breast cancer, according to a gene expression analysis.

Nicholas C. Turner, MD, PhD, of Royal Marsden Hospital and Institute of Cancer Research in London, and his colleagues used a gene expression panel to detect biomarkers related to the efficacy of palbociclib plus fulvestrant in patients with endocrine-pretreated metastatic breast cancer.

“No predictive biomarkers have been identified in randomized trials of CDK4/6 inhibitors,” the researchers wrote in the Journal of Clinical Oncology.

Study participants were randomly assigned to receive either combination palbociclib and fulvestrant (n = 194) or placebo and fulvestrant (n = 108). The primary analysis was completed using data from the PALOMA-3 trial, which included 10 genes selected from a panel search of 2,534 genes.

The association between level of gene expression and efficacy of palbociclib combination therapy was evaluated by way of advanced statistical analysis.

After analysis, the efficacy of palbociclib was found to be reduced with high levels of cyclin E1 mRNA expression compared with low levels (median PFS palbociclib arm, 7.6 vs. 14.1 months; placebo arm, 4.0 vs. 4.8 months; P = .00238).

“These data suggest that CCNE1 mRNA expression may be associated with the benefit from palbociclib in early-stage breast cancer,” they wrote.

The authors acknowledged that one key limitation of the study was that the biomarkers identified may not be relevant to other CDK4/6 inhibitor combinations.

“Additional methodologic and clinical validations are warranted to elucidate the role of CCNE1 mRNA expression as a biomarker of CDK4/6 inhibitor therapy,” they concluded.

The study was supported by Pfizer. The authors reported financial interests with AbbVie, AstraZeneca, Genentech, Novartis, Pfizer, and others.

SOURCE: Turner NC et al. J Clin Oncol. 2019 Feb 26. doi: 10.1200/JCO.18.00925.

Elderly people were significantly more likely to experience a fracture while walking a dog in 2017 than they were in 2004, according to data from the U.S. Consumer Product Safety Commission.

The estimated number of fractures associated with walking a leashed dog was 4,396 in 2017 among those aged 65 years and older, compared with 1,671 in 2004, which is a significant increase, Kevin Pirruccio of the University of Pennsylvania, Philadelphia, and his associates wrote in JAMA Surgery.

Over the entire study period, 2004-2017, almost 79% of all fractures occurred in women and 67% of all patients were treated in the emergency department and released. The most common injury was hip fracture (17.3%), although upper-extremity fractures were more common (52.1%) than those of the lower extremities (29.4%), trunk (10.1%), or head and neck (7.3%), the investigators reported.

“For older adults – especially those living alone and with decreased bone mineral density – the risks associated with walking leashed dogs merit consideration. Even one such injury could result in a potentially lethal hip fracture, lifelong complications, or loss of independence,” they wrote.

The retrospective, cross-sectional analysis involved the Consumer Product Safety Commission’s National Electronic Injury Surveillance System database, which includes approximately 100 hospital emergency departments. The investigators did not report any conflicts of interest.

[email protected]

SOURCE: Pirruccio K et al. JAMA Surg. 2019 Mar 6. doi: 10.1001/jamasurg.2019.0061.

Elderly people were significantly more likely to experience a fracture while walking a dog in 2017 than they were in 2004, according to data from the U.S. Consumer Product Safety Commission.

The estimated number of fractures associated with walking a leashed dog was 4,396 in 2017 among those aged 65 years and older, compared with 1,671 in 2004, which is a significant increase, Kevin Pirruccio of the University of Pennsylvania, Philadelphia, and his associates wrote in JAMA Surgery.

Over the entire study period, 2004-2017, almost 79% of all fractures occurred in women and 67% of all patients were treated in the emergency department and released. The most common injury was hip fracture (17.3%), although upper-extremity fractures were more common (52.1%) than those of the lower extremities (29.4%), trunk (10.1%), or head and neck (7.3%), the investigators reported.

“For older adults – especially those living alone and with decreased bone mineral density – the risks associated with walking leashed dogs merit consideration. Even one such injury could result in a potentially lethal hip fracture, lifelong complications, or loss of independence,” they wrote.

The retrospective, cross-sectional analysis involved the Consumer Product Safety Commission’s National Electronic Injury Surveillance System database, which includes approximately 100 hospital emergency departments. The investigators did not report any conflicts of interest.

[email protected]

SOURCE: Pirruccio K et al. JAMA Surg. 2019 Mar 6. doi: 10.1001/jamasurg.2019.0061.

Elderly people were significantly more likely to experience a fracture while walking a dog in 2017 than they were in 2004, according to data from the U.S. Consumer Product Safety Commission.

The estimated number of fractures associated with walking a leashed dog was 4,396 in 2017 among those aged 65 years and older, compared with 1,671 in 2004, which is a significant increase, Kevin Pirruccio of the University of Pennsylvania, Philadelphia, and his associates wrote in JAMA Surgery.

Over the entire study period, 2004-2017, almost 79% of all fractures occurred in women and 67% of all patients were treated in the emergency department and released. The most common injury was hip fracture (17.3%), although upper-extremity fractures were more common (52.1%) than those of the lower extremities (29.4%), trunk (10.1%), or head and neck (7.3%), the investigators reported.

“For older adults – especially those living alone and with decreased bone mineral density – the risks associated with walking leashed dogs merit consideration. Even one such injury could result in a potentially lethal hip fracture, lifelong complications, or loss of independence,” they wrote.

The retrospective, cross-sectional analysis involved the Consumer Product Safety Commission’s National Electronic Injury Surveillance System database, which includes approximately 100 hospital emergency departments. The investigators did not report any conflicts of interest.

[email protected]

SOURCE: Pirruccio K et al. JAMA Surg. 2019 Mar 6. doi: 10.1001/jamasurg.2019.0061.