SAN DIEGO – The results of a small, single-site study suggest that nitrous oxide (NO) can play a significant role in reducing pain during laser tattoo removal.

“Nitrous oxide is a safe and effective option for patients, particularly those who have large tattoos that can’t be adequately numbed with injections or topical numbing,” the study’s lead author, Jared Mallalieu, DO, said in an interview. “NO has allowed us to treat larger tattoos – full sleeve or large back tattoos – in a single setting, which has made treatment more convenient for patients.”

Patients fared better on pain measures when they received NO, compared with topical and injectable anesthetics, according to Dr. Mallalieu, a cosmetic surgeon at the Laser Center of Maryland, Severna Park. The results were so dramatic that EMLA cream is now rarely used for patients in his clinic, although injectable lidocaine is used on smaller tattoos (smaller than 5 inches by 5 inches), he said.

The use of NO comes with challenges, however, in terms of the extra time and patient monitoring required, he said.

Dr. Mallalieu and his associates reported the results in an e-poster at the annual meeting of the American Society for Laser Medicine and Surgery.

Laser tattoo removal can be an agonizing process. “Patients describe it as being significantly more painful than getting a tattoo,” Dr. Mallalieu said. “The intense pain only lasts during the treatment,” he said, “though many patients will note some discomfort for a few hours after a treatment session.”

Most clinics use a topical cream, such as lidocaine/prilocaine (EMLA) or topical benzocaine/lidocaine/tetracaine (BLT), as an anesthetic for these procedures. “Our center has also used 1% lidocaine with epinephrine in small doses of up to 7 mg/kg,” he said. “The injections are much better than the cream.”

Sometimes the clinic uses a device that blows cold air on the skin, which “helps a little,” he added.

For the study, conducted in 2014, 23 laser tattoo removal patients were surveyed about their pain levels using a 1-10 scale, after undergoing a total of 41 single-location procedures.

[email protected]

SAN DIEGO – The results of a small, single-site study suggest that nitrous oxide (NO) can play a significant role in reducing pain during laser tattoo removal.

“Nitrous oxide is a safe and effective option for patients, particularly those who have large tattoos that can’t be adequately numbed with injections or topical numbing,” the study’s lead author, Jared Mallalieu, DO, said in an interview. “NO has allowed us to treat larger tattoos – full sleeve or large back tattoos – in a single setting, which has made treatment more convenient for patients.”

Patients fared better on pain measures when they received NO, compared with topical and injectable anesthetics, according to Dr. Mallalieu, a cosmetic surgeon at the Laser Center of Maryland, Severna Park. The results were so dramatic that EMLA cream is now rarely used for patients in his clinic, although injectable lidocaine is used on smaller tattoos (smaller than 5 inches by 5 inches), he said.

The use of NO comes with challenges, however, in terms of the extra time and patient monitoring required, he said.

Dr. Mallalieu and his associates reported the results in an e-poster at the annual meeting of the American Society for Laser Medicine and Surgery.

Laser tattoo removal can be an agonizing process. “Patients describe it as being significantly more painful than getting a tattoo,” Dr. Mallalieu said. “The intense pain only lasts during the treatment,” he said, “though many patients will note some discomfort for a few hours after a treatment session.”

Most clinics use a topical cream, such as lidocaine/prilocaine (EMLA) or topical benzocaine/lidocaine/tetracaine (BLT), as an anesthetic for these procedures. “Our center has also used 1% lidocaine with epinephrine in small doses of up to 7 mg/kg,” he said. “The injections are much better than the cream.”

Sometimes the clinic uses a device that blows cold air on the skin, which “helps a little,” he added.

For the study, conducted in 2014, 23 laser tattoo removal patients were surveyed about their pain levels using a 1-10 scale, after undergoing a total of 41 single-location procedures.

[email protected]

SAN DIEGO – The results of a small, single-site study suggest that nitrous oxide (NO) can play a significant role in reducing pain during laser tattoo removal.

“Nitrous oxide is a safe and effective option for patients, particularly those who have large tattoos that can’t be adequately numbed with injections or topical numbing,” the study’s lead author, Jared Mallalieu, DO, said in an interview. “NO has allowed us to treat larger tattoos – full sleeve or large back tattoos – in a single setting, which has made treatment more convenient for patients.”

Patients fared better on pain measures when they received NO, compared with topical and injectable anesthetics, according to Dr. Mallalieu, a cosmetic surgeon at the Laser Center of Maryland, Severna Park. The results were so dramatic that EMLA cream is now rarely used for patients in his clinic, although injectable lidocaine is used on smaller tattoos (smaller than 5 inches by 5 inches), he said.

The use of NO comes with challenges, however, in terms of the extra time and patient monitoring required, he said.

Dr. Mallalieu and his associates reported the results in an e-poster at the annual meeting of the American Society for Laser Medicine and Surgery.

Laser tattoo removal can be an agonizing process. “Patients describe it as being significantly more painful than getting a tattoo,” Dr. Mallalieu said. “The intense pain only lasts during the treatment,” he said, “though many patients will note some discomfort for a few hours after a treatment session.”

Most clinics use a topical cream, such as lidocaine/prilocaine (EMLA) or topical benzocaine/lidocaine/tetracaine (BLT), as an anesthetic for these procedures. “Our center has also used 1% lidocaine with epinephrine in small doses of up to 7 mg/kg,” he said. “The injections are much better than the cream.”

Sometimes the clinic uses a device that blows cold air on the skin, which “helps a little,” he added.

For the study, conducted in 2014, 23 laser tattoo removal patients were surveyed about their pain levels using a 1-10 scale, after undergoing a total of 41 single-location procedures.

[email protected]

NEW YORK – Should the first chimeric antigen receptor (CAR) T-cell treatment receive Food and Drug Administration approval for refractory, aggressive non-Hodgkin lymphoma, possibly before the end of 2017, several thousand U.S. patients will be potential candidates for the treatment, Jeremy S. Abramson, MD, predicted at a conference held by Imedex.

Dr. Abramson has led studies using a CAR T cell that differs from the one furthest along in development. He based his predicted timetable for an approved biologics license of the process, with which he can engineer patient-specific T cells that are under development by Kite Pharma, on the “remarkable” level of complete responses the intervention produced in a pivotal phase II study.

Mitchel L. Zoler/Frontline Medical News

Dr. Abramson has been a consultant to Kite Pharma and to AbbVie, Genentech, Gilead, and Seattle Genetics.

[email protected]

On Twitter @mitchelzoler

NEW YORK – Should the first chimeric antigen receptor (CAR) T-cell treatment receive Food and Drug Administration approval for refractory, aggressive non-Hodgkin lymphoma, possibly before the end of 2017, several thousand U.S. patients will be potential candidates for the treatment, Jeremy S. Abramson, MD, predicted at a conference held by Imedex.

Dr. Abramson has led studies using a CAR T cell that differs from the one furthest along in development. He based his predicted timetable for an approved biologics license of the process, with which he can engineer patient-specific T cells that are under development by Kite Pharma, on the “remarkable” level of complete responses the intervention produced in a pivotal phase II study.

Mitchel L. Zoler/Frontline Medical News

Dr. Abramson has been a consultant to Kite Pharma and to AbbVie, Genentech, Gilead, and Seattle Genetics.

[email protected]

On Twitter @mitchelzoler

NEW YORK – Should the first chimeric antigen receptor (CAR) T-cell treatment receive Food and Drug Administration approval for refractory, aggressive non-Hodgkin lymphoma, possibly before the end of 2017, several thousand U.S. patients will be potential candidates for the treatment, Jeremy S. Abramson, MD, predicted at a conference held by Imedex.

Dr. Abramson has led studies using a CAR T cell that differs from the one furthest along in development. He based his predicted timetable for an approved biologics license of the process, with which he can engineer patient-specific T cells that are under development by Kite Pharma, on the “remarkable” level of complete responses the intervention produced in a pivotal phase II study.

Mitchel L. Zoler/Frontline Medical News

Dr. Abramson has been a consultant to Kite Pharma and to AbbVie, Genentech, Gilead, and Seattle Genetics.

[email protected]

On Twitter @mitchelzoler

Patients with psoriasis may be at a greater risk of melanoma and hematologic cancers, compared with the general population, but treatments do not appear to increase risk, according to Shivani P. Reddy of the University of Illinois at Chicago, and associates.

In a retrospective cohort study, they identified 815,765 patients at Kaiser Permanente Southern California who had at least one medical encounter from January 2004 through December 2013. Of these patients, 8,161 (1%) met the diagnostic and inclusion criteria for psoriasis, and there were 7,167 (0.89%) cases of melanoma and 5,399 (0.66%) cases of lymphoma or leukemia.

Among the patients with psoriasis, there were 62 (0.87%) melanoma cases and 47 (0.87%) cases of lymphoma or leukemia.

Of the 109 patients with psoriasis who went on to develop melanoma or lymphoma, the time to diagnosis of melanoma or hematologic cancers was significantly less for patients with psoriasis than for patients without psoriasis (P = .01). The patients with psoriasis had a 1.53 times higher risk of developing a malignancy compared with patients without psoriasis (P less than .01) in the multivariable Cox proportional hazards model.

“There were no differences between patients with melanoma and hematologic cancer by treatment type,” which were phototherapy, tumor necrosis factor inhibitor therapy, and topical medications, they wrote.

“Our study demonstrates that the risk of hematologic cancer and melanoma is increased in patients with psoriasis over time, although this risk is not impacted by psoriasis therapies,” the researchers concluded. “Defining the risk of malignancy in these patients is important for proper workup and management.”

Read the study in the Journal of the American Academy of Dermatology (doi: 10.1016/j.jaad.2016.09.047).
 

[email protected]

Patients with psoriasis may be at a greater risk of melanoma and hematologic cancers, compared with the general population, but treatments do not appear to increase risk, according to Shivani P. Reddy of the University of Illinois at Chicago, and associates.

In a retrospective cohort study, they identified 815,765 patients at Kaiser Permanente Southern California who had at least one medical encounter from January 2004 through December 2013. Of these patients, 8,161 (1%) met the diagnostic and inclusion criteria for psoriasis, and there were 7,167 (0.89%) cases of melanoma and 5,399 (0.66%) cases of lymphoma or leukemia.

Among the patients with psoriasis, there were 62 (0.87%) melanoma cases and 47 (0.87%) cases of lymphoma or leukemia.

Of the 109 patients with psoriasis who went on to develop melanoma or lymphoma, the time to diagnosis of melanoma or hematologic cancers was significantly less for patients with psoriasis than for patients without psoriasis (P = .01). The patients with psoriasis had a 1.53 times higher risk of developing a malignancy compared with patients without psoriasis (P less than .01) in the multivariable Cox proportional hazards model.

“There were no differences between patients with melanoma and hematologic cancer by treatment type,” which were phototherapy, tumor necrosis factor inhibitor therapy, and topical medications, they wrote.

“Our study demonstrates that the risk of hematologic cancer and melanoma is increased in patients with psoriasis over time, although this risk is not impacted by psoriasis therapies,” the researchers concluded. “Defining the risk of malignancy in these patients is important for proper workup and management.”

Read the study in the Journal of the American Academy of Dermatology (doi: 10.1016/j.jaad.2016.09.047).
 

[email protected]

Patients with psoriasis may be at a greater risk of melanoma and hematologic cancers, compared with the general population, but treatments do not appear to increase risk, according to Shivani P. Reddy of the University of Illinois at Chicago, and associates.

In a retrospective cohort study, they identified 815,765 patients at Kaiser Permanente Southern California who had at least one medical encounter from January 2004 through December 2013. Of these patients, 8,161 (1%) met the diagnostic and inclusion criteria for psoriasis, and there were 7,167 (0.89%) cases of melanoma and 5,399 (0.66%) cases of lymphoma or leukemia.

Among the patients with psoriasis, there were 62 (0.87%) melanoma cases and 47 (0.87%) cases of lymphoma or leukemia.

Of the 109 patients with psoriasis who went on to develop melanoma or lymphoma, the time to diagnosis of melanoma or hematologic cancers was significantly less for patients with psoriasis than for patients without psoriasis (P = .01). The patients with psoriasis had a 1.53 times higher risk of developing a malignancy compared with patients without psoriasis (P less than .01) in the multivariable Cox proportional hazards model.

“There were no differences between patients with melanoma and hematologic cancer by treatment type,” which were phototherapy, tumor necrosis factor inhibitor therapy, and topical medications, they wrote.

“Our study demonstrates that the risk of hematologic cancer and melanoma is increased in patients with psoriasis over time, although this risk is not impacted by psoriasis therapies,” the researchers concluded. “Defining the risk of malignancy in these patients is important for proper workup and management.”

Read the study in the Journal of the American Academy of Dermatology (doi: 10.1016/j.jaad.2016.09.047).
 

[email protected]

Nonlocalized bronchiectasis is becoming more common in developing countries and has been difficult to treat. While surgery for localized bronchiectasis has been proven, its role in nonlocalized disease is less established; researchers from China are advocating for a reexamination of surgical resection in this disease based on results of a small cohort study at their academic center.

“Lobectomy for the predominant lesion is a safe procedure in the surgical treatment of nonlocalized bronchiectasis and leads to significant relief of symptoms with good rates of satisfaction,” Jie Dai, PhD, of Shanghai (China) Pulmonary Hospital Tongji University and his coauthors reported in the Journal of Thoracic and Cardiovascular Surgery (2017 Apr;153:979-85).

The researchers reviewed the medical records of 37 consecutive patients – 10 men and 27 women – with nonlocalized bronchiectasis who had lobectomies via thoracotomies during 2010-2013. Twenty-three patients (62.2%) were symptom free after surgery and 10 (27%) reported that their symptoms had improved. Four (10.8%) said their symptoms either did not improve or worsened, but three of them also had chronic occlusive pulmonary disease. There were no deaths, and the morbidity rate was 21.6%.

The researchers used three criteria to select candidates for surgery: persistent symptoms despite medical treatment; an identifiable predominant lesion; and cardiopulmonary function compatible with anesthetic risk. Average age was 54.5 years and more than half (19) had no smoking history.

The surgical technique involved a posterolateral thoracotomy and a double-lumen endotracheal tube to avoid contamination of the opposite side of the lung during surgery. Surgery avoided excessive bronchial dissection and preserved peribronchial tissues. Extrapleural dissection avoided spillage of lung contents into the pleural space.

Treatment of the hilum followed an order from the pulmonary artery to the pulmonary vein and then to the bronchus. An ultrasonic device helped isolate and then ligate or sever distorted bronchial arteries. A mechanical stapler was used to close the bronchial stump. Reinforcement involved an intercostal muscle flap in 16 cases and a pedicled parietal pleural flap in 21. If any sign of pleural infection appeared after hemostasis, pleural space irrigation with 0.5% neomycin (500 mg/L) was initiated. Two chest drains were placed at the bronchial stump, and the bronchial suture checked with bronchoscopy. Airway secretions were removed, and pathology confirmed bronchiectasis all specimens.

The frequency of acute infection and hemoptysis decreased significantly at 1 year postoperatively, from 5.3% to 1.8% and 4.9% to 1.1%, respectively, (P less than .01 for both). Daily sputum volume decreased an average of 26.3 mL (P less than .01) and sputum cultures became sterile in 13 (35%) of patients (P less than .01).

Previously, surgery for nonlocalized bronchiectasis had been reserved for life-threatening symptoms only, but Dr. Dai and his coauthors fashioned their study on previous studies of lobectomy that included patients with nonlocalized bronchiectasis (Br J Surg. 2005;92:836-9; Ann Thorac Surg. 2003;75:382-7).

Two major complications occurred in the Shanghai cohort: empyema and persistent air leak, both of which were managed without a reoperation and had been reported in previous series. Dr. Dai and his coauthors have adopted protocols to reduce complications, among them, requiring that patients have sputum output greater than 20 mL/day with little purulence and no engorgement or edema in the tunica mucosa bronchiorum on bronchoscopy.

But the researchers are not ready to extend surgery as a blanket indication for nonlocalized bronchiectasis. “It is worth mentioning that the surgical benefit is limited to patients who have only one predominant area of bronchiectatic disease that can be localized by CT instead of those with diffuse bronchiectasis,” they wrote. “The ideal surgical candidate has a heterogeneous distribution of diseased areas.”

The investigators pointed out that the study was limited by its small size and lack of information on etiologies of disease.

Dr. Dai and his coauthors had no financial relationships to disclose.
 

Nonlocalized bronchiectasis is becoming more common in developing countries and has been difficult to treat. While surgery for localized bronchiectasis has been proven, its role in nonlocalized disease is less established; researchers from China are advocating for a reexamination of surgical resection in this disease based on results of a small cohort study at their academic center.

“Lobectomy for the predominant lesion is a safe procedure in the surgical treatment of nonlocalized bronchiectasis and leads to significant relief of symptoms with good rates of satisfaction,” Jie Dai, PhD, of Shanghai (China) Pulmonary Hospital Tongji University and his coauthors reported in the Journal of Thoracic and Cardiovascular Surgery (2017 Apr;153:979-85).

The researchers reviewed the medical records of 37 consecutive patients – 10 men and 27 women – with nonlocalized bronchiectasis who had lobectomies via thoracotomies during 2010-2013. Twenty-three patients (62.2%) were symptom free after surgery and 10 (27%) reported that their symptoms had improved. Four (10.8%) said their symptoms either did not improve or worsened, but three of them also had chronic occlusive pulmonary disease. There were no deaths, and the morbidity rate was 21.6%.

The researchers used three criteria to select candidates for surgery: persistent symptoms despite medical treatment; an identifiable predominant lesion; and cardiopulmonary function compatible with anesthetic risk. Average age was 54.5 years and more than half (19) had no smoking history.

The surgical technique involved a posterolateral thoracotomy and a double-lumen endotracheal tube to avoid contamination of the opposite side of the lung during surgery. Surgery avoided excessive bronchial dissection and preserved peribronchial tissues. Extrapleural dissection avoided spillage of lung contents into the pleural space.

Treatment of the hilum followed an order from the pulmonary artery to the pulmonary vein and then to the bronchus. An ultrasonic device helped isolate and then ligate or sever distorted bronchial arteries. A mechanical stapler was used to close the bronchial stump. Reinforcement involved an intercostal muscle flap in 16 cases and a pedicled parietal pleural flap in 21. If any sign of pleural infection appeared after hemostasis, pleural space irrigation with 0.5% neomycin (500 mg/L) was initiated. Two chest drains were placed at the bronchial stump, and the bronchial suture checked with bronchoscopy. Airway secretions were removed, and pathology confirmed bronchiectasis all specimens.

The frequency of acute infection and hemoptysis decreased significantly at 1 year postoperatively, from 5.3% to 1.8% and 4.9% to 1.1%, respectively, (P less than .01 for both). Daily sputum volume decreased an average of 26.3 mL (P less than .01) and sputum cultures became sterile in 13 (35%) of patients (P less than .01).

Previously, surgery for nonlocalized bronchiectasis had been reserved for life-threatening symptoms only, but Dr. Dai and his coauthors fashioned their study on previous studies of lobectomy that included patients with nonlocalized bronchiectasis (Br J Surg. 2005;92:836-9; Ann Thorac Surg. 2003;75:382-7).

Two major complications occurred in the Shanghai cohort: empyema and persistent air leak, both of which were managed without a reoperation and had been reported in previous series. Dr. Dai and his coauthors have adopted protocols to reduce complications, among them, requiring that patients have sputum output greater than 20 mL/day with little purulence and no engorgement or edema in the tunica mucosa bronchiorum on bronchoscopy.

But the researchers are not ready to extend surgery as a blanket indication for nonlocalized bronchiectasis. “It is worth mentioning that the surgical benefit is limited to patients who have only one predominant area of bronchiectatic disease that can be localized by CT instead of those with diffuse bronchiectasis,” they wrote. “The ideal surgical candidate has a heterogeneous distribution of diseased areas.”

The investigators pointed out that the study was limited by its small size and lack of information on etiologies of disease.

Dr. Dai and his coauthors had no financial relationships to disclose.
 

Nonlocalized bronchiectasis is becoming more common in developing countries and has been difficult to treat. While surgery for localized bronchiectasis has been proven, its role in nonlocalized disease is less established; researchers from China are advocating for a reexamination of surgical resection in this disease based on results of a small cohort study at their academic center.

“Lobectomy for the predominant lesion is a safe procedure in the surgical treatment of nonlocalized bronchiectasis and leads to significant relief of symptoms with good rates of satisfaction,” Jie Dai, PhD, of Shanghai (China) Pulmonary Hospital Tongji University and his coauthors reported in the Journal of Thoracic and Cardiovascular Surgery (2017 Apr;153:979-85).

The researchers reviewed the medical records of 37 consecutive patients – 10 men and 27 women – with nonlocalized bronchiectasis who had lobectomies via thoracotomies during 2010-2013. Twenty-three patients (62.2%) were symptom free after surgery and 10 (27%) reported that their symptoms had improved. Four (10.8%) said their symptoms either did not improve or worsened, but three of them also had chronic occlusive pulmonary disease. There were no deaths, and the morbidity rate was 21.6%.

The researchers used three criteria to select candidates for surgery: persistent symptoms despite medical treatment; an identifiable predominant lesion; and cardiopulmonary function compatible with anesthetic risk. Average age was 54.5 years and more than half (19) had no smoking history.

The surgical technique involved a posterolateral thoracotomy and a double-lumen endotracheal tube to avoid contamination of the opposite side of the lung during surgery. Surgery avoided excessive bronchial dissection and preserved peribronchial tissues. Extrapleural dissection avoided spillage of lung contents into the pleural space.

Treatment of the hilum followed an order from the pulmonary artery to the pulmonary vein and then to the bronchus. An ultrasonic device helped isolate and then ligate or sever distorted bronchial arteries. A mechanical stapler was used to close the bronchial stump. Reinforcement involved an intercostal muscle flap in 16 cases and a pedicled parietal pleural flap in 21. If any sign of pleural infection appeared after hemostasis, pleural space irrigation with 0.5% neomycin (500 mg/L) was initiated. Two chest drains were placed at the bronchial stump, and the bronchial suture checked with bronchoscopy. Airway secretions were removed, and pathology confirmed bronchiectasis all specimens.

The frequency of acute infection and hemoptysis decreased significantly at 1 year postoperatively, from 5.3% to 1.8% and 4.9% to 1.1%, respectively, (P less than .01 for both). Daily sputum volume decreased an average of 26.3 mL (P less than .01) and sputum cultures became sterile in 13 (35%) of patients (P less than .01).

Previously, surgery for nonlocalized bronchiectasis had been reserved for life-threatening symptoms only, but Dr. Dai and his coauthors fashioned their study on previous studies of lobectomy that included patients with nonlocalized bronchiectasis (Br J Surg. 2005;92:836-9; Ann Thorac Surg. 2003;75:382-7).

Two major complications occurred in the Shanghai cohort: empyema and persistent air leak, both of which were managed without a reoperation and had been reported in previous series. Dr. Dai and his coauthors have adopted protocols to reduce complications, among them, requiring that patients have sputum output greater than 20 mL/day with little purulence and no engorgement or edema in the tunica mucosa bronchiorum on bronchoscopy.

But the researchers are not ready to extend surgery as a blanket indication for nonlocalized bronchiectasis. “It is worth mentioning that the surgical benefit is limited to patients who have only one predominant area of bronchiectatic disease that can be localized by CT instead of those with diffuse bronchiectasis,” they wrote. “The ideal surgical candidate has a heterogeneous distribution of diseased areas.”

The investigators pointed out that the study was limited by its small size and lack of information on etiologies of disease.

Dr. Dai and his coauthors had no financial relationships to disclose.
 

Adding the thrombopoietin-receptor agonist eltrombopag to standard immunosuppressive therapy markedly improved the frequency, speed, and robustness of hematologic recovery in a phase I-II trial of patients with severe aplastic anemia, according to a report published online April 20 in the New England Journal of Medicine.

Previously, researchers found that eltrombopag was effective against aplastic anemia that was refractory to immunosuppression, inducing higher platelet counts, hemoglobin levels, and neutrophil numbers when used as a single agent. They then examined whether adding the drug to immunosuppression in treatment-naive patients would improve the response in this nonrandomized prospective trial, said Danielle M. Townsley, MD, of the hematology branch, National Heart, Lung, and Blood Institute, and her associates.

Ninety-two consecutive patients aged 3-82 years were divided into three cohorts with different timing and duration of treatment. Cohort 1 (30 patients) received eltrombopag from day 14 to 6 months; cohort 2 (31 patients) received it from day 14 to 3 months; and cohort 3 (31 patients) received it from day 1 to 6 months.

The primary efficacy endpoint – the rate of complete hematologic response at 6 months – was highest, at 58%, in cohort 3, which had the earliest initiation and the longest duration of eltrombopag treatment. It was lowest, at 26%, in cohort 2, which had the shortest duration of eltrombopag treatment. The rate of complete hematologic response was intermediate in cohort 1, at 33% (N Engl J Med. 2017 Apr 20. doi:10.1056/NEJMoa1613878).

These complete response rates all exceeded those reported historically, which range from 10% to 20%. Moreover, the rate of partial or complete hematologic response was 87% across all three cohorts, compared with the 66% partial or complete response rate that would be expected with standard immunosuppression alone. Absolute neutrophil counts and platelet counts in all three cohorts also were higher at both 3 and 6 months than were those that have been reported historically.

The average time to independence from transfusions in the entire study population was 1 month, and clinically meaningful improvements in neutrophil levels were seen within a few weeks of initiating eltrombopag.

Two cases of severe cutaneous eruptions led to discontinuation of the study drug. Liver abnormalities were frequent but transient and did not limit the use of eltrombopag.

If these results are validated in future studies, and if no unexpected late complications are identified, adding eltrombopag to standard immunosuppressive therapy “may help patients optimize the timing of allogeneic stem-cell transplantation or avoid it. Of particular interest would be use of eltrombopag in combination with less toxic immunosuppressive regimens that omit antithymocyte globulin, particularly in older patients, in patients with coexisting conditions, and in developing countries where aplastic anemia is prevalent and conventional therapies [are] extremely costly,” Dr. Townsley and her associates noted.

One such confirmatory study, a large randomized placebo-controlled trial (NCT02099747), is now underway in Europe, they wrote.

This trial was supported by the National Heart, Lung, and Blood Institute. Dr. Townsley and her associates reported ties to GlaxoSmithKline and Novartis, makers of eltrombopag.

Adding the thrombopoietin-receptor agonist eltrombopag to standard immunosuppressive therapy markedly improved the frequency, speed, and robustness of hematologic recovery in a phase I-II trial of patients with severe aplastic anemia, according to a report published online April 20 in the New England Journal of Medicine.

Previously, researchers found that eltrombopag was effective against aplastic anemia that was refractory to immunosuppression, inducing higher platelet counts, hemoglobin levels, and neutrophil numbers when used as a single agent. They then examined whether adding the drug to immunosuppression in treatment-naive patients would improve the response in this nonrandomized prospective trial, said Danielle M. Townsley, MD, of the hematology branch, National Heart, Lung, and Blood Institute, and her associates.

Ninety-two consecutive patients aged 3-82 years were divided into three cohorts with different timing and duration of treatment. Cohort 1 (30 patients) received eltrombopag from day 14 to 6 months; cohort 2 (31 patients) received it from day 14 to 3 months; and cohort 3 (31 patients) received it from day 1 to 6 months.

The primary efficacy endpoint – the rate of complete hematologic response at 6 months – was highest, at 58%, in cohort 3, which had the earliest initiation and the longest duration of eltrombopag treatment. It was lowest, at 26%, in cohort 2, which had the shortest duration of eltrombopag treatment. The rate of complete hematologic response was intermediate in cohort 1, at 33% (N Engl J Med. 2017 Apr 20. doi:10.1056/NEJMoa1613878).

These complete response rates all exceeded those reported historically, which range from 10% to 20%. Moreover, the rate of partial or complete hematologic response was 87% across all three cohorts, compared with the 66% partial or complete response rate that would be expected with standard immunosuppression alone. Absolute neutrophil counts and platelet counts in all three cohorts also were higher at both 3 and 6 months than were those that have been reported historically.

The average time to independence from transfusions in the entire study population was 1 month, and clinically meaningful improvements in neutrophil levels were seen within a few weeks of initiating eltrombopag.

Two cases of severe cutaneous eruptions led to discontinuation of the study drug. Liver abnormalities were frequent but transient and did not limit the use of eltrombopag.

If these results are validated in future studies, and if no unexpected late complications are identified, adding eltrombopag to standard immunosuppressive therapy “may help patients optimize the timing of allogeneic stem-cell transplantation or avoid it. Of particular interest would be use of eltrombopag in combination with less toxic immunosuppressive regimens that omit antithymocyte globulin, particularly in older patients, in patients with coexisting conditions, and in developing countries where aplastic anemia is prevalent and conventional therapies [are] extremely costly,” Dr. Townsley and her associates noted.

One such confirmatory study, a large randomized placebo-controlled trial (NCT02099747), is now underway in Europe, they wrote.

This trial was supported by the National Heart, Lung, and Blood Institute. Dr. Townsley and her associates reported ties to GlaxoSmithKline and Novartis, makers of eltrombopag.

Adding the thrombopoietin-receptor agonist eltrombopag to standard immunosuppressive therapy markedly improved the frequency, speed, and robustness of hematologic recovery in a phase I-II trial of patients with severe aplastic anemia, according to a report published online April 20 in the New England Journal of Medicine.

Previously, researchers found that eltrombopag was effective against aplastic anemia that was refractory to immunosuppression, inducing higher platelet counts, hemoglobin levels, and neutrophil numbers when used as a single agent. They then examined whether adding the drug to immunosuppression in treatment-naive patients would improve the response in this nonrandomized prospective trial, said Danielle M. Townsley, MD, of the hematology branch, National Heart, Lung, and Blood Institute, and her associates.

Ninety-two consecutive patients aged 3-82 years were divided into three cohorts with different timing and duration of treatment. Cohort 1 (30 patients) received eltrombopag from day 14 to 6 months; cohort 2 (31 patients) received it from day 14 to 3 months; and cohort 3 (31 patients) received it from day 1 to 6 months.

The primary efficacy endpoint – the rate of complete hematologic response at 6 months – was highest, at 58%, in cohort 3, which had the earliest initiation and the longest duration of eltrombopag treatment. It was lowest, at 26%, in cohort 2, which had the shortest duration of eltrombopag treatment. The rate of complete hematologic response was intermediate in cohort 1, at 33% (N Engl J Med. 2017 Apr 20. doi:10.1056/NEJMoa1613878).

These complete response rates all exceeded those reported historically, which range from 10% to 20%. Moreover, the rate of partial or complete hematologic response was 87% across all three cohorts, compared with the 66% partial or complete response rate that would be expected with standard immunosuppression alone. Absolute neutrophil counts and platelet counts in all three cohorts also were higher at both 3 and 6 months than were those that have been reported historically.

The average time to independence from transfusions in the entire study population was 1 month, and clinically meaningful improvements in neutrophil levels were seen within a few weeks of initiating eltrombopag.

Two cases of severe cutaneous eruptions led to discontinuation of the study drug. Liver abnormalities were frequent but transient and did not limit the use of eltrombopag.

If these results are validated in future studies, and if no unexpected late complications are identified, adding eltrombopag to standard immunosuppressive therapy “may help patients optimize the timing of allogeneic stem-cell transplantation or avoid it. Of particular interest would be use of eltrombopag in combination with less toxic immunosuppressive regimens that omit antithymocyte globulin, particularly in older patients, in patients with coexisting conditions, and in developing countries where aplastic anemia is prevalent and conventional therapies [are] extremely costly,” Dr. Townsley and her associates noted.

One such confirmatory study, a large randomized placebo-controlled trial (NCT02099747), is now underway in Europe, they wrote.

This trial was supported by the National Heart, Lung, and Blood Institute. Dr. Townsley and her associates reported ties to GlaxoSmithKline and Novartis, makers of eltrombopag.

A 46-year-old woman went to her family doctor after 3 months of abdominal bloating, fatigue, nausea, vomiting, anorexia, and weight loss. Ultrasound imaging revealed hepatic lesions and a mass in the colon; she was diagnosed with colon cancer. The cancer had metastasized to an extent that complete resection wasn’t possible, so she received palliative-intent therapy for the next 18 months.

Related: Colorectal Screening: Available but Underused

Initially, the patient responded to the treatment but then presented to the emergency department (ED) with a severe headache. A CT scan revealed that the cancer had spread to her brain. However, this time resection was possible, and she recovered well.

Three weeks later the patient was back in the ED with an infection. A new CT scan showed no evidence of abscess (one of the differential diagnoses). A transthoracic echocardiogram showed a right atrial lesion, and further imaging confirmed a lesion in the right atrium. “Unexpectedly,” her clinicians reported, the lesion originated from the distal inferior vena cava (IVC): She had shown no signs of symptoms of pulmonary embolus or occlusion of the IVC.

Related: Strollin’ the Colon: A Collaborated Effort to Provide Education and Screening Outreach for the Improvement of Awareness, Access, and Early Detection of Colorectal Cancer

Tumor thrombus is rarely reported with colorectal cancer cases, so the patient’s clinicians at first thought the mass in the IVC was bland thrombus, managed with anticoagulation alone. The clinicians felt that the assumption was  reasonable, given the link between malignancy and venous thromboembolism; also because the patient had an indwelling central venous catheter. Contrast-enhanced CT scan and contrast-enhanced ultrasound, however, supported the diagnosis of tumor thrombus.

Due to the rarity of tumor thrombus in colorectal cancer, there are no guidelines for diagnosis and management, the clinicians say. In the patient’s case, consultation with cardiologists, radiologists, and gastrointestinal specialists at the cancer center resulted in an offer to extract the thrombus, but the risks and the fact that she was asymptomatic led the patient to decline. She was instead restarted on palliative chemotherapy with heparin in case part of the thrombus was indeed bland thrombus.

The patient’s condition deteriorated over the next 3 months. She and her team agreed that supportive care at home was best. The patient still had no symptoms from the tumor thrombus when she died.

Related: Cancer Prevention and Gastrointestinal Risk

Autopsy supported the suspicion that the original lesion was partly tumor thrombus and partly bland thrombus, reduced by anticoagulation. But autopsy results revealed no embolization of tumor thrombus or bland thrombus into the pulmonary arteries, although there were extensive metastases in the brain, lung, liver, adrenals, and ovaries. Ultimately, the patient’s death was attributed not to the tumor thrombus that extended into the right atrium but to multiorgan failure due to cancer--validating the decisions to not choose surgery for the thrombus.

Source:
Meyers D, Nixon NA, Franko A, Ng D, Tam VC. BMJ Case Rep. 2017;2017:pii:bcr2016218107.
doi: 10.1136/bcr-2016-218107.

A 46-year-old woman went to her family doctor after 3 months of abdominal bloating, fatigue, nausea, vomiting, anorexia, and weight loss. Ultrasound imaging revealed hepatic lesions and a mass in the colon; she was diagnosed with colon cancer. The cancer had metastasized to an extent that complete resection wasn’t possible, so she received palliative-intent therapy for the next 18 months.

Related: Colorectal Screening: Available but Underused

Initially, the patient responded to the treatment but then presented to the emergency department (ED) with a severe headache. A CT scan revealed that the cancer had spread to her brain. However, this time resection was possible, and she recovered well.

Three weeks later the patient was back in the ED with an infection. A new CT scan showed no evidence of abscess (one of the differential diagnoses). A transthoracic echocardiogram showed a right atrial lesion, and further imaging confirmed a lesion in the right atrium. “Unexpectedly,” her clinicians reported, the lesion originated from the distal inferior vena cava (IVC): She had shown no signs of symptoms of pulmonary embolus or occlusion of the IVC.

Related: Strollin’ the Colon: A Collaborated Effort to Provide Education and Screening Outreach for the Improvement of Awareness, Access, and Early Detection of Colorectal Cancer

Tumor thrombus is rarely reported with colorectal cancer cases, so the patient’s clinicians at first thought the mass in the IVC was bland thrombus, managed with anticoagulation alone. The clinicians felt that the assumption was  reasonable, given the link between malignancy and venous thromboembolism; also because the patient had an indwelling central venous catheter. Contrast-enhanced CT scan and contrast-enhanced ultrasound, however, supported the diagnosis of tumor thrombus.

Due to the rarity of tumor thrombus in colorectal cancer, there are no guidelines for diagnosis and management, the clinicians say. In the patient’s case, consultation with cardiologists, radiologists, and gastrointestinal specialists at the cancer center resulted in an offer to extract the thrombus, but the risks and the fact that she was asymptomatic led the patient to decline. She was instead restarted on palliative chemotherapy with heparin in case part of the thrombus was indeed bland thrombus.

The patient’s condition deteriorated over the next 3 months. She and her team agreed that supportive care at home was best. The patient still had no symptoms from the tumor thrombus when she died.

Related: Cancer Prevention and Gastrointestinal Risk

Autopsy supported the suspicion that the original lesion was partly tumor thrombus and partly bland thrombus, reduced by anticoagulation. But autopsy results revealed no embolization of tumor thrombus or bland thrombus into the pulmonary arteries, although there were extensive metastases in the brain, lung, liver, adrenals, and ovaries. Ultimately, the patient’s death was attributed not to the tumor thrombus that extended into the right atrium but to multiorgan failure due to cancer--validating the decisions to not choose surgery for the thrombus.

Source:
Meyers D, Nixon NA, Franko A, Ng D, Tam VC. BMJ Case Rep. 2017;2017:pii:bcr2016218107.
doi: 10.1136/bcr-2016-218107.

A 46-year-old woman went to her family doctor after 3 months of abdominal bloating, fatigue, nausea, vomiting, anorexia, and weight loss. Ultrasound imaging revealed hepatic lesions and a mass in the colon; she was diagnosed with colon cancer. The cancer had metastasized to an extent that complete resection wasn’t possible, so she received palliative-intent therapy for the next 18 months.

Related: Colorectal Screening: Available but Underused

Initially, the patient responded to the treatment but then presented to the emergency department (ED) with a severe headache. A CT scan revealed that the cancer had spread to her brain. However, this time resection was possible, and she recovered well.

Three weeks later the patient was back in the ED with an infection. A new CT scan showed no evidence of abscess (one of the differential diagnoses). A transthoracic echocardiogram showed a right atrial lesion, and further imaging confirmed a lesion in the right atrium. “Unexpectedly,” her clinicians reported, the lesion originated from the distal inferior vena cava (IVC): She had shown no signs of symptoms of pulmonary embolus or occlusion of the IVC.

Related: Strollin’ the Colon: A Collaborated Effort to Provide Education and Screening Outreach for the Improvement of Awareness, Access, and Early Detection of Colorectal Cancer

Tumor thrombus is rarely reported with colorectal cancer cases, so the patient’s clinicians at first thought the mass in the IVC was bland thrombus, managed with anticoagulation alone. The clinicians felt that the assumption was  reasonable, given the link between malignancy and venous thromboembolism; also because the patient had an indwelling central venous catheter. Contrast-enhanced CT scan and contrast-enhanced ultrasound, however, supported the diagnosis of tumor thrombus.

Due to the rarity of tumor thrombus in colorectal cancer, there are no guidelines for diagnosis and management, the clinicians say. In the patient’s case, consultation with cardiologists, radiologists, and gastrointestinal specialists at the cancer center resulted in an offer to extract the thrombus, but the risks and the fact that she was asymptomatic led the patient to decline. She was instead restarted on palliative chemotherapy with heparin in case part of the thrombus was indeed bland thrombus.

The patient’s condition deteriorated over the next 3 months. She and her team agreed that supportive care at home was best. The patient still had no symptoms from the tumor thrombus when she died.

Related: Cancer Prevention and Gastrointestinal Risk

Autopsy supported the suspicion that the original lesion was partly tumor thrombus and partly bland thrombus, reduced by anticoagulation. But autopsy results revealed no embolization of tumor thrombus or bland thrombus into the pulmonary arteries, although there were extensive metastases in the brain, lung, liver, adrenals, and ovaries. Ultimately, the patient’s death was attributed not to the tumor thrombus that extended into the right atrium but to multiorgan failure due to cancer--validating the decisions to not choose surgery for the thrombus.

Source:
Meyers D, Nixon NA, Franko A, Ng D, Tam VC. BMJ Case Rep. 2017;2017:pii:bcr2016218107.
doi: 10.1136/bcr-2016-218107.

Pre-exposure prophylaxis ( PrEP)—just 1 pill every day—can reduce the risk HIV infection by > 90%. A recent study shows that > 40% of chlamydia infections and 42% of gonorrhea infections also could be prevented over the next decade if 40% of homosexual and bisexual men took PrEP for HIV and were tested and treated every 6 months.

The CDC estimates that nearly 500,000 men are at “substantial risk” for HIV infection and could benefit from PrEP. But recent evidence suggests that some men may use condoms less when they are taking PrEP. According to researchers from the CDC and The Rollins School of Public Health at Emory University, PrEP prevented some STIs even with a 40% reduction in condom use.

The CDC recommends testing patients who use PrEP for bacterial STIs at least once every 6 months even if they don’t have symptoms. The study found that increasing STI testing from twice a year to 4 times a year would not dramatically affect the prevention of chlamydia or gonorrhea.

PrEP’s effectiveness in preventing HIV is well documented, the CDC says. The new study shows the “potential impact” that following the CDC’s clinical guidelines for PrEP can have on preventing bacterial STIs as well. But about one third of primary health care providers had not heard of PrEP as recently as 2015, the CDC says. To address that need, the CDC has been leading education efforts targeting providers, offering the guidelines, step-by-step PrEP checklists, and interview guides, along with a hotline to answer providers’ questions about when and how to offer PrEP.

Pre-exposure prophylaxis ( PrEP)—just 1 pill every day—can reduce the risk HIV infection by > 90%. A recent study shows that > 40% of chlamydia infections and 42% of gonorrhea infections also could be prevented over the next decade if 40% of homosexual and bisexual men took PrEP for HIV and were tested and treated every 6 months.

The CDC estimates that nearly 500,000 men are at “substantial risk” for HIV infection and could benefit from PrEP. But recent evidence suggests that some men may use condoms less when they are taking PrEP. According to researchers from the CDC and The Rollins School of Public Health at Emory University, PrEP prevented some STIs even with a 40% reduction in condom use.

The CDC recommends testing patients who use PrEP for bacterial STIs at least once every 6 months even if they don’t have symptoms. The study found that increasing STI testing from twice a year to 4 times a year would not dramatically affect the prevention of chlamydia or gonorrhea.

PrEP’s effectiveness in preventing HIV is well documented, the CDC says. The new study shows the “potential impact” that following the CDC’s clinical guidelines for PrEP can have on preventing bacterial STIs as well. But about one third of primary health care providers had not heard of PrEP as recently as 2015, the CDC says. To address that need, the CDC has been leading education efforts targeting providers, offering the guidelines, step-by-step PrEP checklists, and interview guides, along with a hotline to answer providers’ questions about when and how to offer PrEP.

Pre-exposure prophylaxis ( PrEP)—just 1 pill every day—can reduce the risk HIV infection by > 90%. A recent study shows that > 40% of chlamydia infections and 42% of gonorrhea infections also could be prevented over the next decade if 40% of homosexual and bisexual men took PrEP for HIV and were tested and treated every 6 months.

The CDC estimates that nearly 500,000 men are at “substantial risk” for HIV infection and could benefit from PrEP. But recent evidence suggests that some men may use condoms less when they are taking PrEP. According to researchers from the CDC and The Rollins School of Public Health at Emory University, PrEP prevented some STIs even with a 40% reduction in condom use.

The CDC recommends testing patients who use PrEP for bacterial STIs at least once every 6 months even if they don’t have symptoms. The study found that increasing STI testing from twice a year to 4 times a year would not dramatically affect the prevention of chlamydia or gonorrhea.

PrEP’s effectiveness in preventing HIV is well documented, the CDC says. The new study shows the “potential impact” that following the CDC’s clinical guidelines for PrEP can have on preventing bacterial STIs as well. But about one third of primary health care providers had not heard of PrEP as recently as 2015, the CDC says. To address that need, the CDC has been leading education efforts targeting providers, offering the guidelines, step-by-step PrEP checklists, and interview guides, along with a hotline to answer providers’ questions about when and how to offer PrEP.

Photo courtesy of GSK

Adding eltrombopag to immunosuppressive therapy (IST) can produce high rates of response in treatment-naïve severe aplastic anemia (SAA), according to research published in NEJM.

In patients who received eltrombopag for 6 months, the overall response rate (ORR) was 94%, and the complete response (CR) rate was 58%.

Researchers noted that these rates are “markedly higher” than response rates observed in historical controls who received IST alone.

The team also said the safety profile of eltrombopag in this study was consistent with the known safety profile of the drug.

“[E]ltrombopag plus standard immunosuppressive therapy appeared to increase the overall response rate and substantially increase the frequency, speed, and robustness of hematologic recovery in patients with SAA compared to historical controls,” said study author Danielle Townsley, MD, of the National Heart, Lung and Blood Institute (NHLBI).

She and her colleagues at NHLBI conducted this research through a Cooperative Research and Development Agreement with Novartis, the company that markets eltrombopag as Promacta/Revolade.

Patients and treatment

This phase 1/2 trial included 92 patients with treatment-naïve SAA. The patients’ median age was 32 (range, 3-82), and 54% of them were male.

At baseline, the patients’ median neutrophil count was 310/mm³ (range, 0-1810), their median reticulocyte count was 19,950/mm³ (range, 1600-60,400), and their median platelet count was 9000/mm³ (range, 0-37,000). Their median thrombopoietin level was 3163 pg/ml (range, 1806-4955).

All patients received horse antithymocyte globulin on days 1 to 4 and cyclosporine from day 1 to 6 months. The patients also received eltrombopag at an age-dependent dose.

They received eltrombopag at 150 mg daily if they were 12 years or older, 75 mg daily if they were 6 to 11, and 2.5 mg/kg/day if they were 2 to 5 years of age.

Patients were also split into 3 cohorts according to treatment duration:

• Cohort 1 received eltrombopag from day 14 to the 6-month mark.
• Cohort 2 received eltrombopag from day 14 to the 3-month mark.
• Cohort 3 received eltrombopag from day 1 to 6 months.

Response

The study’s primary efficacy endpoint was hematologic CR at 6 months. CR was defined as an absolute neutrophil count of at least 1000/mm³, a hemoglobin level of at least 10 g/dL, and a platelet count of at least 100,000/mm³.

Secondary endpoints included partial response (PR) and ORR, among other endpoints. ORR was the rate of CR plus PR. Patients had a PR if they had blood counts that no longer met the criteria for SAA but they did not meet criteria for CR.

For all cohorts, at 6 months, the ORR was 87%, and the CR rate was 39%.

In cohort 1, the ORR was 80%, and the CR rate was 33%.

In cohort 2, the ORR was 87%, and the CR rate was 26%.

In cohort 3, the ORR was 94%, and the CR rate was 58%.

The researchers noted that ORRs were higher across all cohorts than the ORR observed in a historical cohort (66%). The cohort consisted of 102 patients who had received standard IST while serving as controls in 1 of 2 recent NHLBI clinical trials.

Relapse

Thirty-two percent of responding patients (25/78) relapsed after 6 months.

After the study protocol was amended to allow the continuation of low-dose cyclosporine from 6 months to 2 years, the frequency of relapse decreased.

Fourteen percent of responders receiving low-dose cyclosporine beyond 6 months relapsed (6/43), compared to 54% of patients who stopped cyclosporine at 6 months (19/35).

Restarting full-dose cyclosporine reversed relapse and increased blood counts in 13 of 25 patients. Adding eltrombopag reversed relapse in an additional 10 patients.

Survival

The 2-year overall survival rate was 97% for the entire study population and 99% when data were censored for transplant.

Twelve patients under went transplant after eltrombopag. Six of them had not responded or were still transfusion-dependent, 3 relapsed, and 3 had clonal evolution.

Three patients died—1 while on study and 2 after transplant.

Clonal evolution and PNH

The researchers said the frequency of clonal evolution in this study was similar to that observed in the historical cohort of patients who received standard IST. The rate of clonal evolution at 2 years was 8% in both groups.

In the current study, 7 patients had clonal evolution at 2 years. Five patients had loss of chromosome 7, which was associated with dysplastic bone marrow changes in 3 patients.

One patient with a complex karyotype progressed to acute myeloid leukemia.

Two patients developed hemolytic paroxysmal nocturnal hemoglobinuria (PNH).

Safety

Two severe adverse events (AEs) were attributed to eltrombopag. Both were cutaneous eruptions—a grade 2 and a grade 3 event. Both AEs led to discontinuation of the drug.

Seven patients briefly stopped taking eltrombopag during the first 2 weeks of treatment due to transient elevations in liver enzymes.

AEs not attributed to eltrombopag were neutropenic infections and AEs known to be associated with IST.

The single patient who died on study was a non-responder who died 3 months after starting treatment. The death was due to paraneoplastic encephalopathy, which was attributed to thymoma that predated study entry.

Photo courtesy of GSK

Adding eltrombopag to immunosuppressive therapy (IST) can produce high rates of response in treatment-naïve severe aplastic anemia (SAA), according to research published in NEJM.

In patients who received eltrombopag for 6 months, the overall response rate (ORR) was 94%, and the complete response (CR) rate was 58%.

Researchers noted that these rates are “markedly higher” than response rates observed in historical controls who received IST alone.

The team also said the safety profile of eltrombopag in this study was consistent with the known safety profile of the drug.

“[E]ltrombopag plus standard immunosuppressive therapy appeared to increase the overall response rate and substantially increase the frequency, speed, and robustness of hematologic recovery in patients with SAA compared to historical controls,” said study author Danielle Townsley, MD, of the National Heart, Lung and Blood Institute (NHLBI).

She and her colleagues at NHLBI conducted this research through a Cooperative Research and Development Agreement with Novartis, the company that markets eltrombopag as Promacta/Revolade.

Patients and treatment

This phase 1/2 trial included 92 patients with treatment-naïve SAA. The patients’ median age was 32 (range, 3-82), and 54% of them were male.

At baseline, the patients’ median neutrophil count was 310/mm³ (range, 0-1810), their median reticulocyte count was 19,950/mm³ (range, 1600-60,400), and their median platelet count was 9000/mm³ (range, 0-37,000). Their median thrombopoietin level was 3163 pg/ml (range, 1806-4955).

All patients received horse antithymocyte globulin on days 1 to 4 and cyclosporine from day 1 to 6 months. The patients also received eltrombopag at an age-dependent dose.

They received eltrombopag at 150 mg daily if they were 12 years or older, 75 mg daily if they were 6 to 11, and 2.5 mg/kg/day if they were 2 to 5 years of age.

Patients were also split into 3 cohorts according to treatment duration:

• Cohort 1 received eltrombopag from day 14 to the 6-month mark.
• Cohort 2 received eltrombopag from day 14 to the 3-month mark.
• Cohort 3 received eltrombopag from day 1 to 6 months.

Response

The study’s primary efficacy endpoint was hematologic CR at 6 months. CR was defined as an absolute neutrophil count of at least 1000/mm³, a hemoglobin level of at least 10 g/dL, and a platelet count of at least 100,000/mm³.

Secondary endpoints included partial response (PR) and ORR, among other endpoints. ORR was the rate of CR plus PR. Patients had a PR if they had blood counts that no longer met the criteria for SAA but they did not meet criteria for CR.

For all cohorts, at 6 months, the ORR was 87%, and the CR rate was 39%.

In cohort 1, the ORR was 80%, and the CR rate was 33%.

In cohort 2, the ORR was 87%, and the CR rate was 26%.

In cohort 3, the ORR was 94%, and the CR rate was 58%.

The researchers noted that ORRs were higher across all cohorts than the ORR observed in a historical cohort (66%). The cohort consisted of 102 patients who had received standard IST while serving as controls in 1 of 2 recent NHLBI clinical trials.

Relapse

Thirty-two percent of responding patients (25/78) relapsed after 6 months.

After the study protocol was amended to allow the continuation of low-dose cyclosporine from 6 months to 2 years, the frequency of relapse decreased.

Fourteen percent of responders receiving low-dose cyclosporine beyond 6 months relapsed (6/43), compared to 54% of patients who stopped cyclosporine at 6 months (19/35).

Restarting full-dose cyclosporine reversed relapse and increased blood counts in 13 of 25 patients. Adding eltrombopag reversed relapse in an additional 10 patients.

Survival

The 2-year overall survival rate was 97% for the entire study population and 99% when data were censored for transplant.

Twelve patients under went transplant after eltrombopag. Six of them had not responded or were still transfusion-dependent, 3 relapsed, and 3 had clonal evolution.

Three patients died—1 while on study and 2 after transplant.

Clonal evolution and PNH

The researchers said the frequency of clonal evolution in this study was similar to that observed in the historical cohort of patients who received standard IST. The rate of clonal evolution at 2 years was 8% in both groups.

In the current study, 7 patients had clonal evolution at 2 years. Five patients had loss of chromosome 7, which was associated with dysplastic bone marrow changes in 3 patients.

One patient with a complex karyotype progressed to acute myeloid leukemia.

Two patients developed hemolytic paroxysmal nocturnal hemoglobinuria (PNH).

Safety

Two severe adverse events (AEs) were attributed to eltrombopag. Both were cutaneous eruptions—a grade 2 and a grade 3 event. Both AEs led to discontinuation of the drug.

Seven patients briefly stopped taking eltrombopag during the first 2 weeks of treatment due to transient elevations in liver enzymes.

AEs not attributed to eltrombopag were neutropenic infections and AEs known to be associated with IST.

The single patient who died on study was a non-responder who died 3 months after starting treatment. The death was due to paraneoplastic encephalopathy, which was attributed to thymoma that predated study entry.

Photo courtesy of GSK

Adding eltrombopag to immunosuppressive therapy (IST) can produce high rates of response in treatment-naïve severe aplastic anemia (SAA), according to research published in NEJM.

In patients who received eltrombopag for 6 months, the overall response rate (ORR) was 94%, and the complete response (CR) rate was 58%.

Researchers noted that these rates are “markedly higher” than response rates observed in historical controls who received IST alone.

The team also said the safety profile of eltrombopag in this study was consistent with the known safety profile of the drug.

“[E]ltrombopag plus standard immunosuppressive therapy appeared to increase the overall response rate and substantially increase the frequency, speed, and robustness of hematologic recovery in patients with SAA compared to historical controls,” said study author Danielle Townsley, MD, of the National Heart, Lung and Blood Institute (NHLBI).

She and her colleagues at NHLBI conducted this research through a Cooperative Research and Development Agreement with Novartis, the company that markets eltrombopag as Promacta/Revolade.

Patients and treatment

This phase 1/2 trial included 92 patients with treatment-naïve SAA. The patients’ median age was 32 (range, 3-82), and 54% of them were male.

At baseline, the patients’ median neutrophil count was 310/mm³ (range, 0-1810), their median reticulocyte count was 19,950/mm³ (range, 1600-60,400), and their median platelet count was 9000/mm³ (range, 0-37,000). Their median thrombopoietin level was 3163 pg/ml (range, 1806-4955).

All patients received horse antithymocyte globulin on days 1 to 4 and cyclosporine from day 1 to 6 months. The patients also received eltrombopag at an age-dependent dose.

They received eltrombopag at 150 mg daily if they were 12 years or older, 75 mg daily if they were 6 to 11, and 2.5 mg/kg/day if they were 2 to 5 years of age.

Patients were also split into 3 cohorts according to treatment duration:

• Cohort 1 received eltrombopag from day 14 to the 6-month mark.
• Cohort 2 received eltrombopag from day 14 to the 3-month mark.
• Cohort 3 received eltrombopag from day 1 to 6 months.

Response

The study’s primary efficacy endpoint was hematologic CR at 6 months. CR was defined as an absolute neutrophil count of at least 1000/mm³, a hemoglobin level of at least 10 g/dL, and a platelet count of at least 100,000/mm³.

Secondary endpoints included partial response (PR) and ORR, among other endpoints. ORR was the rate of CR plus PR. Patients had a PR if they had blood counts that no longer met the criteria for SAA but they did not meet criteria for CR.

For all cohorts, at 6 months, the ORR was 87%, and the CR rate was 39%.

In cohort 1, the ORR was 80%, and the CR rate was 33%.

In cohort 2, the ORR was 87%, and the CR rate was 26%.

In cohort 3, the ORR was 94%, and the CR rate was 58%.

The researchers noted that ORRs were higher across all cohorts than the ORR observed in a historical cohort (66%). The cohort consisted of 102 patients who had received standard IST while serving as controls in 1 of 2 recent NHLBI clinical trials.

Relapse

Thirty-two percent of responding patients (25/78) relapsed after 6 months.

After the study protocol was amended to allow the continuation of low-dose cyclosporine from 6 months to 2 years, the frequency of relapse decreased.

Fourteen percent of responders receiving low-dose cyclosporine beyond 6 months relapsed (6/43), compared to 54% of patients who stopped cyclosporine at 6 months (19/35).

Restarting full-dose cyclosporine reversed relapse and increased blood counts in 13 of 25 patients. Adding eltrombopag reversed relapse in an additional 10 patients.

Survival

The 2-year overall survival rate was 97% for the entire study population and 99% when data were censored for transplant.

Twelve patients under went transplant after eltrombopag. Six of them had not responded or were still transfusion-dependent, 3 relapsed, and 3 had clonal evolution.

Three patients died—1 while on study and 2 after transplant.

Clonal evolution and PNH

The researchers said the frequency of clonal evolution in this study was similar to that observed in the historical cohort of patients who received standard IST. The rate of clonal evolution at 2 years was 8% in both groups.

In the current study, 7 patients had clonal evolution at 2 years. Five patients had loss of chromosome 7, which was associated with dysplastic bone marrow changes in 3 patients.

One patient with a complex karyotype progressed to acute myeloid leukemia.

Two patients developed hemolytic paroxysmal nocturnal hemoglobinuria (PNH).

Safety

Two severe adverse events (AEs) were attributed to eltrombopag. Both were cutaneous eruptions—a grade 2 and a grade 3 event. Both AEs led to discontinuation of the drug.

Seven patients briefly stopped taking eltrombopag during the first 2 weeks of treatment due to transient elevations in liver enzymes.

AEs not attributed to eltrombopag were neutropenic infections and AEs known to be associated with IST.

The single patient who died on study was a non-responder who died 3 months after starting treatment. The death was due to paraneoplastic encephalopathy, which was attributed to thymoma that predated study entry.

Lab mouse

Cutting certain amino acids from the diet slows tumor growth and prolongs survival in mouse models of malignancy, according to research published in Nature.

Researchers found that removing 2 non-essential amino acids—serine and glycine (SG)—from the diet of mice slowed the development of lymphoma and intestinal cancer.

The SG-free diet also made lymphoma more susceptible to reactive oxygen species (ROS).

As chemotherapy and radiotherapy boost levels of ROS, the researchers believe an SG-free diet could make conventional cancer treatments more effective.

“Our findings suggest that restricting specific amino acids through a controlled diet plan could be an additional part of treatment for some cancer patients in future, helping to make other treatments more effective,” said study author Oliver Maddocks, PhD, of the University of Glasgow in the UK.

He and his colleagues tested the SG-free diet in mouse models of lymphoma (Eμ-Myc) and observed decreased tumor volume and lymphoma cell numbers as well as a significant improvement in survival compared to controls.

The median survival (from the time of diet change at day 60) was 192 days for mice on the SG-free diet and 59 days for mice on the control diet (P=0.0367).

To test whether increasing ROS could enhance the anticancer effects of the SG-free diet, the researchers crossed Eμ-Myc mice with mice that don’t express Tigar, a protein that can support tumor development by limiting ROS.

The researchers found that Tigar ^-/- mice on the SG-free diet had significantly better survival than Tigar ^-/- mice on the control diet (P=0.0451).

The median survival was 50.5 days for Tigar ^+/+ mice on the control diet, 80 days for Tigar ^+/+ mice on the SG-free diet, 107 days for Tigar ^-/- mice on the control diet, and 226 days for Tigar ^-/- mice on the SG-free diet.

The researchers also found the SG-free diet was less effective in cancers with an activated Kras gene (such as prostate cancer) because the faulty gene boosted the cancer cells’ ability to make their own serine and glycine. The team said this could help in selecting which tumors could be best targeted by diet therapy.

“This is a really interesting look at how cutting off the supply of nutrients essential to cancer cell growth and division could help restrain tumors,” said Emma Smith, PhD, of Cancer Research UK, which funded this study.

“The next steps are clinical trials in people to see if giving a specialized diet that lacks these amino acids is safe and helps slow tumor growth as seen in mice. We’d also need to work out which patients are most likely to benefit, depending on the characteristics of their cancer.”

Lab mouse

Cutting certain amino acids from the diet slows tumor growth and prolongs survival in mouse models of malignancy, according to research published in Nature.

Researchers found that removing 2 non-essential amino acids—serine and glycine (SG)—from the diet of mice slowed the development of lymphoma and intestinal cancer.

The SG-free diet also made lymphoma more susceptible to reactive oxygen species (ROS).

As chemotherapy and radiotherapy boost levels of ROS, the researchers believe an SG-free diet could make conventional cancer treatments more effective.

“Our findings suggest that restricting specific amino acids through a controlled diet plan could be an additional part of treatment for some cancer patients in future, helping to make other treatments more effective,” said study author Oliver Maddocks, PhD, of the University of Glasgow in the UK.

He and his colleagues tested the SG-free diet in mouse models of lymphoma (Eμ-Myc) and observed decreased tumor volume and lymphoma cell numbers as well as a significant improvement in survival compared to controls.

The median survival (from the time of diet change at day 60) was 192 days for mice on the SG-free diet and 59 days for mice on the control diet (P=0.0367).

To test whether increasing ROS could enhance the anticancer effects of the SG-free diet, the researchers crossed Eμ-Myc mice with mice that don’t express Tigar, a protein that can support tumor development by limiting ROS.

The researchers found that Tigar ^-/- mice on the SG-free diet had significantly better survival than Tigar ^-/- mice on the control diet (P=0.0451).

The median survival was 50.5 days for Tigar ^+/+ mice on the control diet, 80 days for Tigar ^+/+ mice on the SG-free diet, 107 days for Tigar ^-/- mice on the control diet, and 226 days for Tigar ^-/- mice on the SG-free diet.

The researchers also found the SG-free diet was less effective in cancers with an activated Kras gene (such as prostate cancer) because the faulty gene boosted the cancer cells’ ability to make their own serine and glycine. The team said this could help in selecting which tumors could be best targeted by diet therapy.

“This is a really interesting look at how cutting off the supply of nutrients essential to cancer cell growth and division could help restrain tumors,” said Emma Smith, PhD, of Cancer Research UK, which funded this study.

“The next steps are clinical trials in people to see if giving a specialized diet that lacks these amino acids is safe and helps slow tumor growth as seen in mice. We’d also need to work out which patients are most likely to benefit, depending on the characteristics of their cancer.”

Lab mouse

Cutting certain amino acids from the diet slows tumor growth and prolongs survival in mouse models of malignancy, according to research published in Nature.

Researchers found that removing 2 non-essential amino acids—serine and glycine (SG)—from the diet of mice slowed the development of lymphoma and intestinal cancer.

The SG-free diet also made lymphoma more susceptible to reactive oxygen species (ROS).

As chemotherapy and radiotherapy boost levels of ROS, the researchers believe an SG-free diet could make conventional cancer treatments more effective.

“Our findings suggest that restricting specific amino acids through a controlled diet plan could be an additional part of treatment for some cancer patients in future, helping to make other treatments more effective,” said study author Oliver Maddocks, PhD, of the University of Glasgow in the UK.

He and his colleagues tested the SG-free diet in mouse models of lymphoma (Eμ-Myc) and observed decreased tumor volume and lymphoma cell numbers as well as a significant improvement in survival compared to controls.

The median survival (from the time of diet change at day 60) was 192 days for mice on the SG-free diet and 59 days for mice on the control diet (P=0.0367).

To test whether increasing ROS could enhance the anticancer effects of the SG-free diet, the researchers crossed Eμ-Myc mice with mice that don’t express Tigar, a protein that can support tumor development by limiting ROS.

The researchers found that Tigar ^-/- mice on the SG-free diet had significantly better survival than Tigar ^-/- mice on the control diet (P=0.0451).

The median survival was 50.5 days for Tigar ^+/+ mice on the control diet, 80 days for Tigar ^+/+ mice on the SG-free diet, 107 days for Tigar ^-/- mice on the control diet, and 226 days for Tigar ^-/- mice on the SG-free diet.

The researchers also found the SG-free diet was less effective in cancers with an activated Kras gene (such as prostate cancer) because the faulty gene boosted the cancer cells’ ability to make their own serine and glycine. The team said this could help in selecting which tumors could be best targeted by diet therapy.

“This is a really interesting look at how cutting off the supply of nutrients essential to cancer cell growth and division could help restrain tumors,” said Emma Smith, PhD, of Cancer Research UK, which funded this study.

“The next steps are clinical trials in people to see if giving a specialized diet that lacks these amino acids is safe and helps slow tumor growth as seen in mice. We’d also need to work out which patients are most likely to benefit, depending on the characteristics of their cancer.”

Photo by Daniel Gay

A new type of hemoglobin-based oxygen carrier has shown early promise as a potential blood substitute, according to researchers.

The team created nanoparticles consisting of bovine hemoglobin coated with the polymer polydopamine (PDA).

Lab tests showed that hemoglobin-PDA nanoparticles effectively carried oxygen, caused minimal cell damage, and acted as antioxidants, scavenging for potentially damaging free radicals and reactive oxygen species (ROS).

Hong Zhou, PhD, of the Beijing Institute of Transfusion Medicine in China, and colleagues reported these results in Biomacromolecules.

Past attempts to develop chemically modified hemoglobin as a blood substitute have been hindered by the formation of methemoglobin.

Methemoglobin doesn’t bind oxygen and therefore decreases the amount of oxygen blood delivers in the body. In addition, the generation of methemoglobin produces hydrogen peroxide, which leads to cell damage.

Dr Zhou and colleagues wanted to see if packaging hemoglobin in a benign envelope could prevent these problems. So the team developed a one-step method for wrapping hemoglobin—extracted from bovine red cells—in PDA.

The researchers said their simple preparation method meant the nanoparticles maintained the integrity of hemoglobin’s chemical structure without introducing any toxic reagent.

In addition, the PDA coating allowed hemoglobin to maintain its oxygen-carrying ability by preventing the formation of methemoglobin.

The researchers found the hemoglobin-PDA nanoparticles to have “excellent antioxidant capacity,” as they scavenged free radicals. The team said the ABTS+ radical scavenging rate reached 89%, and the DPPH radical scavenging rate reached 49%.

The hemoglobin-PDA nanoparticles also demonstrated antioxidant capacity by suppressing ROS generation. They reduced hydrogen peroxide-induced ROS generation in H9c2 cells.

Furthermore, the hemoglobin-PDA nanoparticles had little effect on blood constituents and cell viability.

The researchers found the nanoparticles had minimal effects on platelet aggregation, hemolysis in red blood cells, and coagulation processes.

And the nanoparticles had no significant cytotoxic effects on human umbilical vein endothelial cells.

The researchers therefore concluded that their hemoglobin-PDA nanoparticles represent “promising progress” for hemoglobin-based oxygen carriers.

Photo by Daniel Gay

A new type of hemoglobin-based oxygen carrier has shown early promise as a potential blood substitute, according to researchers.

The team created nanoparticles consisting of bovine hemoglobin coated with the polymer polydopamine (PDA).

Lab tests showed that hemoglobin-PDA nanoparticles effectively carried oxygen, caused minimal cell damage, and acted as antioxidants, scavenging for potentially damaging free radicals and reactive oxygen species (ROS).

Hong Zhou, PhD, of the Beijing Institute of Transfusion Medicine in China, and colleagues reported these results in Biomacromolecules.

Past attempts to develop chemically modified hemoglobin as a blood substitute have been hindered by the formation of methemoglobin.

Methemoglobin doesn’t bind oxygen and therefore decreases the amount of oxygen blood delivers in the body. In addition, the generation of methemoglobin produces hydrogen peroxide, which leads to cell damage.

Dr Zhou and colleagues wanted to see if packaging hemoglobin in a benign envelope could prevent these problems. So the team developed a one-step method for wrapping hemoglobin—extracted from bovine red cells—in PDA.

The researchers said their simple preparation method meant the nanoparticles maintained the integrity of hemoglobin’s chemical structure without introducing any toxic reagent.

In addition, the PDA coating allowed hemoglobin to maintain its oxygen-carrying ability by preventing the formation of methemoglobin.

The researchers found the hemoglobin-PDA nanoparticles to have “excellent antioxidant capacity,” as they scavenged free radicals. The team said the ABTS+ radical scavenging rate reached 89%, and the DPPH radical scavenging rate reached 49%.

The hemoglobin-PDA nanoparticles also demonstrated antioxidant capacity by suppressing ROS generation. They reduced hydrogen peroxide-induced ROS generation in H9c2 cells.

Furthermore, the hemoglobin-PDA nanoparticles had little effect on blood constituents and cell viability.

The researchers found the nanoparticles had minimal effects on platelet aggregation, hemolysis in red blood cells, and coagulation processes.

And the nanoparticles had no significant cytotoxic effects on human umbilical vein endothelial cells.

The researchers therefore concluded that their hemoglobin-PDA nanoparticles represent “promising progress” for hemoglobin-based oxygen carriers.

Photo by Daniel Gay

A new type of hemoglobin-based oxygen carrier has shown early promise as a potential blood substitute, according to researchers.

The team created nanoparticles consisting of bovine hemoglobin coated with the polymer polydopamine (PDA).

Lab tests showed that hemoglobin-PDA nanoparticles effectively carried oxygen, caused minimal cell damage, and acted as antioxidants, scavenging for potentially damaging free radicals and reactive oxygen species (ROS).

Hong Zhou, PhD, of the Beijing Institute of Transfusion Medicine in China, and colleagues reported these results in Biomacromolecules.

Past attempts to develop chemically modified hemoglobin as a blood substitute have been hindered by the formation of methemoglobin.

Methemoglobin doesn’t bind oxygen and therefore decreases the amount of oxygen blood delivers in the body. In addition, the generation of methemoglobin produces hydrogen peroxide, which leads to cell damage.

Dr Zhou and colleagues wanted to see if packaging hemoglobin in a benign envelope could prevent these problems. So the team developed a one-step method for wrapping hemoglobin—extracted from bovine red cells—in PDA.

The researchers said their simple preparation method meant the nanoparticles maintained the integrity of hemoglobin’s chemical structure without introducing any toxic reagent.

In addition, the PDA coating allowed hemoglobin to maintain its oxygen-carrying ability by preventing the formation of methemoglobin.

The researchers found the hemoglobin-PDA nanoparticles to have “excellent antioxidant capacity,” as they scavenged free radicals. The team said the ABTS+ radical scavenging rate reached 89%, and the DPPH radical scavenging rate reached 49%.

The hemoglobin-PDA nanoparticles also demonstrated antioxidant capacity by suppressing ROS generation. They reduced hydrogen peroxide-induced ROS generation in H9c2 cells.

Furthermore, the hemoglobin-PDA nanoparticles had little effect on blood constituents and cell viability.

The researchers found the nanoparticles had minimal effects on platelet aggregation, hemolysis in red blood cells, and coagulation processes.

And the nanoparticles had no significant cytotoxic effects on human umbilical vein endothelial cells.

The researchers therefore concluded that their hemoglobin-PDA nanoparticles represent “promising progress” for hemoglobin-based oxygen carriers.