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Anticoagulant granted fast track designation
Image by Kevin MacKenzie
The US Food and Drug Administration (FDA) has granted fast track designation to betrixaban as extended-duration venous thromboembolism (VTE) prophylaxis for acute medically ill patients.
This includes patients who are hospitalized for serious medical conditions such as heart failure, stroke, infection, and pulmonary disease.
Betrixaban is an investigational oral anticoagulant that directly inhibits the activity of factor Xa.
According to Portola Pharmaceuticals, the company developing betrixaban, the drug has distinct properties that may allow it to demonstrate clinical benefit without significantly increasing the risk of fatal bleeding and certain other serious side effects.
These benefits include a 19- to 25-hour half-life for once-daily dosing, a low peak-to-trough drug concentration ratio that minimizes anticoagulant variability, low renal clearance, and no significant CYP3A4 metabolism, which may reduce the risk of drug-drug interactions.
Betrixaban trials
In the phase 2 Explore-Xa trial, researchers compared betrixaban and warfarin in patients with atrial fibrillation. The team randomized 508 patients to 1 of 3 blinded doses of betrixaban (40 mg, 60 mg, or 80 mg once daily) or unblinded warfarin, adjusted to an international normalized ratio of 2.0-3.0.
The primary outcome was major or clinically relevant non-major bleeding. At a mean follow-up of 147 days, the primary outcome had been met by 1 patient in the 40 mg betrixaban arm, 5 each in the 60 mg and 80 mg betrixaban arms, and 7 in the warfarin arm.
One patient each in the 60 mg and 80 mg arms experienced an ischemic stroke. And there were 2 vascular deaths, 1 each in the 40 mg arm and the warfarin arm.
In the phase 2 EXPERT trial, researchers compared betrixaban and enoxaparin as VTE prophylaxis in patients who underwent total knee replacement.
The team enrolled 215 patients and assigned them to 1 of 3 post-operative prophylaxis regimens: betrixaban at 15 mg twice daily, betrixaban at 40 mg twice daily, or enoxaparin at 30 mg every 12 hours—all for 10 to 14 days.
The primary efficacy outcome was the incidence of VTE during the dosing period, and 175 patients were evaluable for this outcome. VTE occurred in 20% of patients in the 15 mg betrixaban arm (14/70), 15% in the 40 mg betrixaban arm (10/65), and 10% (4/40) in the enoxaparin arm.
Safety outcomes included major and clinically significant non-major bleeds through 48 hours after treatment. There were no bleeds in the 15 mg betrixaban arm, 2 (2.4%) clinically significant non-major bleeds in the 40 mg betrixaban arm, and 1 (2.3%) major bleed and 2 (4.6%) clinically significant non-major bleeds in the enoxaparin arm.
Betrixaban is currently being tested in the phase 3 APEX trial for the prevention of VTE in acute medically ill patients. Portola said it expects to complete enrollment in APEX by the end of this year and report top-line data in the first quarter of 2016.
If the trial is successful, the company plans to submit a new drug application to the FDA later in 2016 under the fast track designation.
About fast track designation
The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers. 
Image by Kevin MacKenzie
The US Food and Drug Administration (FDA) has granted fast track designation to betrixaban as extended-duration venous thromboembolism (VTE) prophylaxis for acute medically ill patients.
This includes patients who are hospitalized for serious medical conditions such as heart failure, stroke, infection, and pulmonary disease.
Betrixaban is an investigational oral anticoagulant that directly inhibits the activity of factor Xa.
According to Portola Pharmaceuticals, the company developing betrixaban, the drug has distinct properties that may allow it to demonstrate clinical benefit without significantly increasing the risk of fatal bleeding and certain other serious side effects.
These benefits include a 19- to 25-hour half-life for once-daily dosing, a low peak-to-trough drug concentration ratio that minimizes anticoagulant variability, low renal clearance, and no significant CYP3A4 metabolism, which may reduce the risk of drug-drug interactions.
Betrixaban trials
In the phase 2 Explore-Xa trial, researchers compared betrixaban and warfarin in patients with atrial fibrillation. The team randomized 508 patients to 1 of 3 blinded doses of betrixaban (40 mg, 60 mg, or 80 mg once daily) or unblinded warfarin, adjusted to an international normalized ratio of 2.0-3.0.
The primary outcome was major or clinically relevant non-major bleeding. At a mean follow-up of 147 days, the primary outcome had been met by 1 patient in the 40 mg betrixaban arm, 5 each in the 60 mg and 80 mg betrixaban arms, and 7 in the warfarin arm.
One patient each in the 60 mg and 80 mg arms experienced an ischemic stroke. And there were 2 vascular deaths, 1 each in the 40 mg arm and the warfarin arm.
In the phase 2 EXPERT trial, researchers compared betrixaban and enoxaparin as VTE prophylaxis in patients who underwent total knee replacement.
The team enrolled 215 patients and assigned them to 1 of 3 post-operative prophylaxis regimens: betrixaban at 15 mg twice daily, betrixaban at 40 mg twice daily, or enoxaparin at 30 mg every 12 hours—all for 10 to 14 days.
The primary efficacy outcome was the incidence of VTE during the dosing period, and 175 patients were evaluable for this outcome. VTE occurred in 20% of patients in the 15 mg betrixaban arm (14/70), 15% in the 40 mg betrixaban arm (10/65), and 10% (4/40) in the enoxaparin arm.
Safety outcomes included major and clinically significant non-major bleeds through 48 hours after treatment. There were no bleeds in the 15 mg betrixaban arm, 2 (2.4%) clinically significant non-major bleeds in the 40 mg betrixaban arm, and 1 (2.3%) major bleed and 2 (4.6%) clinically significant non-major bleeds in the enoxaparin arm.
Betrixaban is currently being tested in the phase 3 APEX trial for the prevention of VTE in acute medically ill patients. Portola said it expects to complete enrollment in APEX by the end of this year and report top-line data in the first quarter of 2016.
If the trial is successful, the company plans to submit a new drug application to the FDA later in 2016 under the fast track designation.
About fast track designation
The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers.
Image by Kevin MacKenzie
The US Food and Drug Administration (FDA) has granted fast track designation to betrixaban as extended-duration venous thromboembolism (VTE) prophylaxis for acute medically ill patients.
This includes patients who are hospitalized for serious medical conditions such as heart failure, stroke, infection, and pulmonary disease.
Betrixaban is an investigational oral anticoagulant that directly inhibits the activity of factor Xa.
According to Portola Pharmaceuticals, the company developing betrixaban, the drug has distinct properties that may allow it to demonstrate clinical benefit without significantly increasing the risk of fatal bleeding and certain other serious side effects.
These benefits include a 19- to 25-hour half-life for once-daily dosing, a low peak-to-trough drug concentration ratio that minimizes anticoagulant variability, low renal clearance, and no significant CYP3A4 metabolism, which may reduce the risk of drug-drug interactions.
Betrixaban trials
In the phase 2 Explore-Xa trial, researchers compared betrixaban and warfarin in patients with atrial fibrillation. The team randomized 508 patients to 1 of 3 blinded doses of betrixaban (40 mg, 60 mg, or 80 mg once daily) or unblinded warfarin, adjusted to an international normalized ratio of 2.0-3.0.
The primary outcome was major or clinically relevant non-major bleeding. At a mean follow-up of 147 days, the primary outcome had been met by 1 patient in the 40 mg betrixaban arm, 5 each in the 60 mg and 80 mg betrixaban arms, and 7 in the warfarin arm.
One patient each in the 60 mg and 80 mg arms experienced an ischemic stroke. And there were 2 vascular deaths, 1 each in the 40 mg arm and the warfarin arm.
In the phase 2 EXPERT trial, researchers compared betrixaban and enoxaparin as VTE prophylaxis in patients who underwent total knee replacement.
The team enrolled 215 patients and assigned them to 1 of 3 post-operative prophylaxis regimens: betrixaban at 15 mg twice daily, betrixaban at 40 mg twice daily, or enoxaparin at 30 mg every 12 hours—all for 10 to 14 days.
The primary efficacy outcome was the incidence of VTE during the dosing period, and 175 patients were evaluable for this outcome. VTE occurred in 20% of patients in the 15 mg betrixaban arm (14/70), 15% in the 40 mg betrixaban arm (10/65), and 10% (4/40) in the enoxaparin arm.
Safety outcomes included major and clinically significant non-major bleeds through 48 hours after treatment. There were no bleeds in the 15 mg betrixaban arm, 2 (2.4%) clinically significant non-major bleeds in the 40 mg betrixaban arm, and 1 (2.3%) major bleed and 2 (4.6%) clinically significant non-major bleeds in the enoxaparin arm.
Betrixaban is currently being tested in the phase 3 APEX trial for the prevention of VTE in acute medically ill patients. Portola said it expects to complete enrollment in APEX by the end of this year and report top-line data in the first quarter of 2016.
If the trial is successful, the company plans to submit a new drug application to the FDA later in 2016 under the fast track designation.
About fast track designation
The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers.
Cancer survivors have poor diets, study suggests
New research suggests that cancer survivors in the US may need dietary interventions to improve their health.
The study showed that, overall, cancer survivors did not adhere to federal dietary guidelines as well as a matched control population.
Cancer survivors tended to consume more empty calories and less fiber than controls.
Fang Fang Zhang, MD, PhD, of Tufts University in Boston, Massachusetts, and his colleagues reported these findings in Cancer.
The team evaluated the diets of 1533 adult cancer survivors who participated in the National Health and Nutrition Examination Survey from 1999 to 2010. The investigators also assessed the diets of 3075 individuals who had no history of cancer and were matched to the cancer survivors by age, sex, and race/ethnicity.
The goal was to determine how subjects’ diets aligned with advice from the 2010 Dietary Guidelines for Americans, which was jointly issued by the Department of Agriculture and the Department of Health and Human Services.
Cancer survivors had poor adherence to the guidelines, with a total Healthy Eating Index score of 47.2 out of 100, compared with a score of 48.3 in the adults without a history of cancer (P=0.03).
Cancer survivors had a significantly lower mean score for empty calories compared to the noncancer group—13.6 and 14.4, respectively (P=0.001). This suggested the cancer group had a higher consumption of calories from solid fats, alcohol, and added sugars.
Cancer survivors also had significantly lower dietary intake of fiber than the noncancer group—15.0 and 15.9 g per day, respectively (P=0.02).
Compared to recommended values, cancer survivors had low dietary intakes of vitamin D (31% of the recommended intake), vitamin E (47%), potassium (55%), and calcium (73%) but high intakes of saturated fat (112%) and sodium (133%).
The investigators noted that diet quality in cancer survivors increased linearly with age. The older the age, the better the diet quality.
Survivors with lower education (high school or less) had significantly worse diet quality than those with higher education. And survivors who were current smokers had significantly worse diet quality than non-smokers or former smokers.
For the 4 major cancer types in the US (breast, prostate, lung, and colorectal), breast cancer survivors had the best diet quality, and lung cancer survivors had the worst diet quality.
The investigators said that knowing how well cancer survivors adhere to federal dietary guidelines can help inform evidence-based priorities for improving their nutritional intake.
“Dietary changes that include more fiber, fruit, and vegetables in the diet and less fat, sodium, and added sugar would be important for cancer survivors,” Dr Zhang said.
“Oncology care providers can play critical roles in reinforcing the importance of a healthful diet and can refer patients to registered dietitians who are experts in oncology care or to other reputable sources in order to improve survivors’ overall health.”
New research suggests that cancer survivors in the US may need dietary interventions to improve their health.
The study showed that, overall, cancer survivors did not adhere to federal dietary guidelines as well as a matched control population.
Cancer survivors tended to consume more empty calories and less fiber than controls.
Fang Fang Zhang, MD, PhD, of Tufts University in Boston, Massachusetts, and his colleagues reported these findings in Cancer.
The team evaluated the diets of 1533 adult cancer survivors who participated in the National Health and Nutrition Examination Survey from 1999 to 2010. The investigators also assessed the diets of 3075 individuals who had no history of cancer and were matched to the cancer survivors by age, sex, and race/ethnicity.
The goal was to determine how subjects’ diets aligned with advice from the 2010 Dietary Guidelines for Americans, which was jointly issued by the Department of Agriculture and the Department of Health and Human Services.
Cancer survivors had poor adherence to the guidelines, with a total Healthy Eating Index score of 47.2 out of 100, compared with a score of 48.3 in the adults without a history of cancer (P=0.03).
Cancer survivors had a significantly lower mean score for empty calories compared to the noncancer group—13.6 and 14.4, respectively (P=0.001). This suggested the cancer group had a higher consumption of calories from solid fats, alcohol, and added sugars.
Cancer survivors also had significantly lower dietary intake of fiber than the noncancer group—15.0 and 15.9 g per day, respectively (P=0.02).
Compared to recommended values, cancer survivors had low dietary intakes of vitamin D (31% of the recommended intake), vitamin E (47%), potassium (55%), and calcium (73%) but high intakes of saturated fat (112%) and sodium (133%).
The investigators noted that diet quality in cancer survivors increased linearly with age. The older the age, the better the diet quality.
Survivors with lower education (high school or less) had significantly worse diet quality than those with higher education. And survivors who were current smokers had significantly worse diet quality than non-smokers or former smokers.
For the 4 major cancer types in the US (breast, prostate, lung, and colorectal), breast cancer survivors had the best diet quality, and lung cancer survivors had the worst diet quality.
The investigators said that knowing how well cancer survivors adhere to federal dietary guidelines can help inform evidence-based priorities for improving their nutritional intake.
“Dietary changes that include more fiber, fruit, and vegetables in the diet and less fat, sodium, and added sugar would be important for cancer survivors,” Dr Zhang said.
“Oncology care providers can play critical roles in reinforcing the importance of a healthful diet and can refer patients to registered dietitians who are experts in oncology care or to other reputable sources in order to improve survivors’ overall health.”
New research suggests that cancer survivors in the US may need dietary interventions to improve their health.
The study showed that, overall, cancer survivors did not adhere to federal dietary guidelines as well as a matched control population.
Cancer survivors tended to consume more empty calories and less fiber than controls.
Fang Fang Zhang, MD, PhD, of Tufts University in Boston, Massachusetts, and his colleagues reported these findings in Cancer.
The team evaluated the diets of 1533 adult cancer survivors who participated in the National Health and Nutrition Examination Survey from 1999 to 2010. The investigators also assessed the diets of 3075 individuals who had no history of cancer and were matched to the cancer survivors by age, sex, and race/ethnicity.
The goal was to determine how subjects’ diets aligned with advice from the 2010 Dietary Guidelines for Americans, which was jointly issued by the Department of Agriculture and the Department of Health and Human Services.
Cancer survivors had poor adherence to the guidelines, with a total Healthy Eating Index score of 47.2 out of 100, compared with a score of 48.3 in the adults without a history of cancer (P=0.03).
Cancer survivors had a significantly lower mean score for empty calories compared to the noncancer group—13.6 and 14.4, respectively (P=0.001). This suggested the cancer group had a higher consumption of calories from solid fats, alcohol, and added sugars.
Cancer survivors also had significantly lower dietary intake of fiber than the noncancer group—15.0 and 15.9 g per day, respectively (P=0.02).
Compared to recommended values, cancer survivors had low dietary intakes of vitamin D (31% of the recommended intake), vitamin E (47%), potassium (55%), and calcium (73%) but high intakes of saturated fat (112%) and sodium (133%).
The investigators noted that diet quality in cancer survivors increased linearly with age. The older the age, the better the diet quality.
Survivors with lower education (high school or less) had significantly worse diet quality than those with higher education. And survivors who were current smokers had significantly worse diet quality than non-smokers or former smokers.
For the 4 major cancer types in the US (breast, prostate, lung, and colorectal), breast cancer survivors had the best diet quality, and lung cancer survivors had the worst diet quality.
The investigators said that knowing how well cancer survivors adhere to federal dietary guidelines can help inform evidence-based priorities for improving their nutritional intake.
“Dietary changes that include more fiber, fruit, and vegetables in the diet and less fat, sodium, and added sugar would be important for cancer survivors,” Dr Zhang said.
“Oncology care providers can play critical roles in reinforcing the importance of a healthful diet and can refer patients to registered dietitians who are experts in oncology care or to other reputable sources in order to improve survivors’ overall health.”
Tracking system helps reduce blood use
Photo by Juan D. Alfonso
CHICAGO—Researchers say an electronic tracking system has enabled a group of hospitals to significantly reduce the amount of blood transfused after operations.
This system also cut costs by an estimated $2.5 million over 2 years and contributed to lower infection rates without harming patients.
These results were presented at the 2015 Clinical Congress of the American College of Surgeons and published in the Journal of the American College of Surgeons.
In 2012, Intermountain Healthcare implemented the blood ordering and tracking system, along with a program to educate hospital staff, in 22 hospitals across Utah. This includes trauma centers, small rural hospitals, and large community medical centers.
Intermountain employs approximately 1200 physicians and 550 advanced practice clinicians, and another 3000 to 4000 independent physicians have privileges at Intermountain hospitals.
Before Intermountain implemented its blood tracking system, general surgeons, orthopedic surgeons, and urologists each used different hematocrit levels to order blood.
Now, Intermountain uses a consistent threshold across all disciplines—less than 23%. However, physicians can still order blood for patients with hematocrit above that threshold when they feel it is medically necessary.
Results
In 2011, 6% of all patients at Intermountain facilities received blood. Today, only 4% do, according to study author Mark J. Ott, MD, chief medical director of Intermountain Healthcare’s central region.
“So a third of our patients didn’t get blood who used to,” Dr Ott said. “That’s a giant change. That’s tens of thousands of units of blood a year that didn’t get used.”
Before the program started (January 1, 2012), Intermountain facilities transfused almost 50 units of packed red blood cells per 1000 patient days. By January 31, 2015, that rate had declined to about 35.5 units, a reduction of around 30%.
Over the same time period, the percentage of patients transfused with a hematocrit of 23% or greater decreased from 60% to 34%.
The researchers said these reductions in blood use reduced costs by about $2.5 million over the 2-year period, assuming each unit of packed red blood cells costs $300.
In addition, the rate of hospital-acquired infections for both the general hospital population and patients who received blood declined significantly over the 2-year period.
The overall infection rate fell from 1.66 to 0.81 per 1000 patient days. Among patients who received blood, infection rates declined around 33%.
Dr Ott noted that the reduction in infections was also impacted by other initiatives within the health system aimed at reducing surgical site infections and ambulating patients earlier after operations.
“So I cannot tell you that those decreases in hospital-acquired infections are solely due to patients receiving less blood, but it’s part of the picture,” he said. “And we did not see worse outcomes in patients.”
Photo by Juan D. Alfonso
CHICAGO—Researchers say an electronic tracking system has enabled a group of hospitals to significantly reduce the amount of blood transfused after operations.
This system also cut costs by an estimated $2.5 million over 2 years and contributed to lower infection rates without harming patients.
These results were presented at the 2015 Clinical Congress of the American College of Surgeons and published in the Journal of the American College of Surgeons.
In 2012, Intermountain Healthcare implemented the blood ordering and tracking system, along with a program to educate hospital staff, in 22 hospitals across Utah. This includes trauma centers, small rural hospitals, and large community medical centers.
Intermountain employs approximately 1200 physicians and 550 advanced practice clinicians, and another 3000 to 4000 independent physicians have privileges at Intermountain hospitals.
Before Intermountain implemented its blood tracking system, general surgeons, orthopedic surgeons, and urologists each used different hematocrit levels to order blood.
Now, Intermountain uses a consistent threshold across all disciplines—less than 23%. However, physicians can still order blood for patients with hematocrit above that threshold when they feel it is medically necessary.
Results
In 2011, 6% of all patients at Intermountain facilities received blood. Today, only 4% do, according to study author Mark J. Ott, MD, chief medical director of Intermountain Healthcare’s central region.
“So a third of our patients didn’t get blood who used to,” Dr Ott said. “That’s a giant change. That’s tens of thousands of units of blood a year that didn’t get used.”
Before the program started (January 1, 2012), Intermountain facilities transfused almost 50 units of packed red blood cells per 1000 patient days. By January 31, 2015, that rate had declined to about 35.5 units, a reduction of around 30%.
Over the same time period, the percentage of patients transfused with a hematocrit of 23% or greater decreased from 60% to 34%.
The researchers said these reductions in blood use reduced costs by about $2.5 million over the 2-year period, assuming each unit of packed red blood cells costs $300.
In addition, the rate of hospital-acquired infections for both the general hospital population and patients who received blood declined significantly over the 2-year period.
The overall infection rate fell from 1.66 to 0.81 per 1000 patient days. Among patients who received blood, infection rates declined around 33%.
Dr Ott noted that the reduction in infections was also impacted by other initiatives within the health system aimed at reducing surgical site infections and ambulating patients earlier after operations.
“So I cannot tell you that those decreases in hospital-acquired infections are solely due to patients receiving less blood, but it’s part of the picture,” he said. “And we did not see worse outcomes in patients.”
Photo by Juan D. Alfonso
CHICAGO—Researchers say an electronic tracking system has enabled a group of hospitals to significantly reduce the amount of blood transfused after operations.
This system also cut costs by an estimated $2.5 million over 2 years and contributed to lower infection rates without harming patients.
These results were presented at the 2015 Clinical Congress of the American College of Surgeons and published in the Journal of the American College of Surgeons.
In 2012, Intermountain Healthcare implemented the blood ordering and tracking system, along with a program to educate hospital staff, in 22 hospitals across Utah. This includes trauma centers, small rural hospitals, and large community medical centers.
Intermountain employs approximately 1200 physicians and 550 advanced practice clinicians, and another 3000 to 4000 independent physicians have privileges at Intermountain hospitals.
Before Intermountain implemented its blood tracking system, general surgeons, orthopedic surgeons, and urologists each used different hematocrit levels to order blood.
Now, Intermountain uses a consistent threshold across all disciplines—less than 23%. However, physicians can still order blood for patients with hematocrit above that threshold when they feel it is medically necessary.
Results
In 2011, 6% of all patients at Intermountain facilities received blood. Today, only 4% do, according to study author Mark J. Ott, MD, chief medical director of Intermountain Healthcare’s central region.
“So a third of our patients didn’t get blood who used to,” Dr Ott said. “That’s a giant change. That’s tens of thousands of units of blood a year that didn’t get used.”
Before the program started (January 1, 2012), Intermountain facilities transfused almost 50 units of packed red blood cells per 1000 patient days. By January 31, 2015, that rate had declined to about 35.5 units, a reduction of around 30%.
Over the same time period, the percentage of patients transfused with a hematocrit of 23% or greater decreased from 60% to 34%.
The researchers said these reductions in blood use reduced costs by about $2.5 million over the 2-year period, assuming each unit of packed red blood cells costs $300.
In addition, the rate of hospital-acquired infections for both the general hospital population and patients who received blood declined significantly over the 2-year period.
The overall infection rate fell from 1.66 to 0.81 per 1000 patient days. Among patients who received blood, infection rates declined around 33%.
Dr Ott noted that the reduction in infections was also impacted by other initiatives within the health system aimed at reducing surgical site infections and ambulating patients earlier after operations.
“So I cannot tell you that those decreases in hospital-acquired infections are solely due to patients receiving less blood, but it’s part of the picture,” he said. “And we did not see worse outcomes in patients.”
Eltrombopag can benefit kids with chronic ITP
Photo by Logan Tuttle
Results of 2 studies suggest eltrombopag can be safe and effective in children of all ages affected by chronic immune thrombocytopenia (ITP).
In both trials, patients who received eltrombopag were significantly more likely to achieve stable platelet counts than patients who received placebo.
And eltrombopag did not increase the rate of serious adverse events (AEs).
These studies are the phase 2 PETIT trial, which was published in The Lancet Haematology, and the phase 3 PETIT2 trial, which was published in The Lancet.
“The studies, funded by GlaxoSmithKline, provide clinicians with much-needed evidence to help decide when eltrombopag would benefit pediatric patients and provide dosage regimens suitable for pediatric patients,” said investigator John Grainger, PhD, of The University of Manchester in the UK.
Phase 2 trial
The PETIT trial included 67 ITP patients who were stratified by age cohort (12-17 years, 6-11 years, and 1-5 years) and randomized (2:1) to receive eltrombopag or placebo for 7 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 109/L.
The primary efficacy endpoint was the proportion of subjects achieving platelet counts of 50 x 109/L or higher at least once between days 8 and 43 of the randomized period of the study.
Significantly more patients in the eltrombopag arm met this endpoint—62.2%—compared to 31.8% in the placebo arm (P=0.011).
The most common AEs (in the eltrombopag and placebo groups, respectively) were headache (30% vs 43%), upper respiratory tract infection (25% vs 10%), and diarrhea (16% vs 5%).
Grade 3/4 AEs occurred in 11% of patients receiving eltrombopag and 19% of patients receiving placebo. Serious AEs occurred in 9% and 10%, respectively. There were no thrombotic events or malignancies in either group.
Phase 3 trial
The PETIT2 trial included 92 patients with chronic ITP who were randomized (2:1) to receive eltrombopag or placebo for 13 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 109/L.
The primary efficacy endpoint was the proportion of subjects who achieved platelet counts of 50 x 109/L or higher for at least 6 out of 8 weeks, between weeks 5 and 12 of the randomized period.
Significantly more patients in the eltrombopag arm met this endpoint—41.3%, compared to 3.4% of patients in the placebo arm (P<0.001).
AEs that occurred more frequently with eltrombopag than with placebo included nasopharyngitis (17%), rhinitis (16%), upper respiratory tract infection (11%), and cough (11%).
Serious AEs occurred in 8% of patients who received eltrombopag and 14% who received placebo. There were no deaths, malignancies, or thromboses during this trial.
It was based on these studies that eltrombopag was approved for use in US children older than 1 year of age. The drug is currently under review for this indication in the European Union.
Photo by Logan Tuttle
Results of 2 studies suggest eltrombopag can be safe and effective in children of all ages affected by chronic immune thrombocytopenia (ITP).
In both trials, patients who received eltrombopag were significantly more likely to achieve stable platelet counts than patients who received placebo.
And eltrombopag did not increase the rate of serious adverse events (AEs).
These studies are the phase 2 PETIT trial, which was published in The Lancet Haematology, and the phase 3 PETIT2 trial, which was published in The Lancet.
“The studies, funded by GlaxoSmithKline, provide clinicians with much-needed evidence to help decide when eltrombopag would benefit pediatric patients and provide dosage regimens suitable for pediatric patients,” said investigator John Grainger, PhD, of The University of Manchester in the UK.
Phase 2 trial
The PETIT trial included 67 ITP patients who were stratified by age cohort (12-17 years, 6-11 years, and 1-5 years) and randomized (2:1) to receive eltrombopag or placebo for 7 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 109/L.
The primary efficacy endpoint was the proportion of subjects achieving platelet counts of 50 x 109/L or higher at least once between days 8 and 43 of the randomized period of the study.
Significantly more patients in the eltrombopag arm met this endpoint—62.2%—compared to 31.8% in the placebo arm (P=0.011).
The most common AEs (in the eltrombopag and placebo groups, respectively) were headache (30% vs 43%), upper respiratory tract infection (25% vs 10%), and diarrhea (16% vs 5%).
Grade 3/4 AEs occurred in 11% of patients receiving eltrombopag and 19% of patients receiving placebo. Serious AEs occurred in 9% and 10%, respectively. There were no thrombotic events or malignancies in either group.
Phase 3 trial
The PETIT2 trial included 92 patients with chronic ITP who were randomized (2:1) to receive eltrombopag or placebo for 13 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 109/L.
The primary efficacy endpoint was the proportion of subjects who achieved platelet counts of 50 x 109/L or higher for at least 6 out of 8 weeks, between weeks 5 and 12 of the randomized period.
Significantly more patients in the eltrombopag arm met this endpoint—41.3%, compared to 3.4% of patients in the placebo arm (P<0.001).
AEs that occurred more frequently with eltrombopag than with placebo included nasopharyngitis (17%), rhinitis (16%), upper respiratory tract infection (11%), and cough (11%).
Serious AEs occurred in 8% of patients who received eltrombopag and 14% who received placebo. There were no deaths, malignancies, or thromboses during this trial.
It was based on these studies that eltrombopag was approved for use in US children older than 1 year of age. The drug is currently under review for this indication in the European Union.
Photo by Logan Tuttle
Results of 2 studies suggest eltrombopag can be safe and effective in children of all ages affected by chronic immune thrombocytopenia (ITP).
In both trials, patients who received eltrombopag were significantly more likely to achieve stable platelet counts than patients who received placebo.
And eltrombopag did not increase the rate of serious adverse events (AEs).
These studies are the phase 2 PETIT trial, which was published in The Lancet Haematology, and the phase 3 PETIT2 trial, which was published in The Lancet.
“The studies, funded by GlaxoSmithKline, provide clinicians with much-needed evidence to help decide when eltrombopag would benefit pediatric patients and provide dosage regimens suitable for pediatric patients,” said investigator John Grainger, PhD, of The University of Manchester in the UK.
Phase 2 trial
The PETIT trial included 67 ITP patients who were stratified by age cohort (12-17 years, 6-11 years, and 1-5 years) and randomized (2:1) to receive eltrombopag or placebo for 7 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 109/L.
The primary efficacy endpoint was the proportion of subjects achieving platelet counts of 50 x 109/L or higher at least once between days 8 and 43 of the randomized period of the study.
Significantly more patients in the eltrombopag arm met this endpoint—62.2%—compared to 31.8% in the placebo arm (P=0.011).
The most common AEs (in the eltrombopag and placebo groups, respectively) were headache (30% vs 43%), upper respiratory tract infection (25% vs 10%), and diarrhea (16% vs 5%).
Grade 3/4 AEs occurred in 11% of patients receiving eltrombopag and 19% of patients receiving placebo. Serious AEs occurred in 9% and 10%, respectively. There were no thrombotic events or malignancies in either group.
Phase 3 trial
The PETIT2 trial included 92 patients with chronic ITP who were randomized (2:1) to receive eltrombopag or placebo for 13 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 109/L.
The primary efficacy endpoint was the proportion of subjects who achieved platelet counts of 50 x 109/L or higher for at least 6 out of 8 weeks, between weeks 5 and 12 of the randomized period.
Significantly more patients in the eltrombopag arm met this endpoint—41.3%, compared to 3.4% of patients in the placebo arm (P<0.001).
AEs that occurred more frequently with eltrombopag than with placebo included nasopharyngitis (17%), rhinitis (16%), upper respiratory tract infection (11%), and cough (11%).
Serious AEs occurred in 8% of patients who received eltrombopag and 14% who received placebo. There were no deaths, malignancies, or thromboses during this trial.
It was based on these studies that eltrombopag was approved for use in US children older than 1 year of age. The drug is currently under review for this indication in the European Union.
Regimen may lengthen survival in AL amyloidosis
High-dose melphalan and autologous stem cell transplant (HDM/SCT) may enable long-term survival in patients with light-chain (AL) amyloidosis, according to research published in Blood.
The study included more than 500 patients who were followed for a median of 8 years, and the median overall survival (OS) was 7.63 years.
Patients tended to live longer if they had a hematologic complete response (CR) to treatment and if they received the full dose of melphalan as opposed to a modified dose.
“While survival is strongly dependent upon achieving hematologic CR, the survival of patients who did not achieve a CR and of those who relapsed after CR is notable, suggesting a benefit of aggressive treatment,” said Vaishali Sanchorawala, MD, of Boston University School of Medicine in Massachusetts.
Dr Sanchorawala and her colleagues conducted this study by analyzing data from 629 patients with AL amyloidosis who received HDM/SCT between 1994 and 2014. The patients’ median age was 57 (range, 28 to 80).
They received full-dose melphalan at 200 mg/m2 (n=350, 55.6%) or modified-dose melphalan at 100-140 mg/m2 (n=279, 44.3%), based on their age and organ function. All patients received growth factor for stem cell mobilization.
Treatment-related mortality (TRM) was defined as death within 100 days of SCT. The rate of TRM was 7.4% (n=47). Eleven deaths occurred during stem cell mobilization and collection (before melphalan was given).
After 2005, there were no deaths during stem cell mobilization and collection, and TRM improved to 3.4% (n=10).
Overall, 543 patients (86.3%) were evaluable for response at 6 to 12 months after SCT. Of these patients, 40.3% (n=219) achieved a hematologic CR. However, 18.2% (n=40) of these patients later relapsed, at a median of 3.97 years (range, 1.89-12.45).
Hematologic CR was more likely among patients who received full-dose melphalan than those who received the modified dose, occurring in 44.9% and 33.7% of patients, respectively (P=0.0091).
Relapse was more likely among patients who received melphalan at the modified dose than the full dose, occurring in 60% and 40%, respectively.
At a median follow-up of 8 years, the median OS was 7.63 years. The median OS has not been reached among patients achieving a hematologic CR, but it was 6.3 years for patients who did not achieve a hematologic CR (P<0.0001). The median OS for patients who relapsed was 4.3 years.
The median OS was significantly longer for patients who received full-dose melphalan—10.47 years, compared to 5.15 years for patients who received the modified dose (P<0.0001).
Likewise, the estimated OS rates at 1, 5, 10, and 15 years were higher for patients with a hematologic CR than for those without one. The 1-year OS is 100% and 94%, respectively. The OS at 5 years is 88% and 60%, respectively. The 10-year OS is 72% and 34%, respectively. And the OS at 15 years is 57% and 18%, respectively.
Forty patients who achieved a hematologic CR died of a cause other than relapse, including sudden death (n=7), metastatic malignancy (n=6), heart failure (n=5), renal failure (n=5), therapy-related myelodysplastic syndrome/acute myeloid leukemia (n=4), sepsis (n=4), stroke (n=3), bleeding complications (n=2), and unknown cause (n=4).
“Strategies to better understand which patients may benefit the most from this treatment and reducing treatment-related mortality, as well as using combination therapies with novel agents to increase the CR rate, will likely improve outcomes in the future for patients who, just a few years ago, were considered to have a rapidly fatal diagnosis,” Dr Sanchorawala said.
She and her colleagues also noted that this study included a “highly selected” group of new patients.
High-dose melphalan and autologous stem cell transplant (HDM/SCT) may enable long-term survival in patients with light-chain (AL) amyloidosis, according to research published in Blood.
The study included more than 500 patients who were followed for a median of 8 years, and the median overall survival (OS) was 7.63 years.
Patients tended to live longer if they had a hematologic complete response (CR) to treatment and if they received the full dose of melphalan as opposed to a modified dose.
“While survival is strongly dependent upon achieving hematologic CR, the survival of patients who did not achieve a CR and of those who relapsed after CR is notable, suggesting a benefit of aggressive treatment,” said Vaishali Sanchorawala, MD, of Boston University School of Medicine in Massachusetts.
Dr Sanchorawala and her colleagues conducted this study by analyzing data from 629 patients with AL amyloidosis who received HDM/SCT between 1994 and 2014. The patients’ median age was 57 (range, 28 to 80).
They received full-dose melphalan at 200 mg/m2 (n=350, 55.6%) or modified-dose melphalan at 100-140 mg/m2 (n=279, 44.3%), based on their age and organ function. All patients received growth factor for stem cell mobilization.
Treatment-related mortality (TRM) was defined as death within 100 days of SCT. The rate of TRM was 7.4% (n=47). Eleven deaths occurred during stem cell mobilization and collection (before melphalan was given).
After 2005, there were no deaths during stem cell mobilization and collection, and TRM improved to 3.4% (n=10).
Overall, 543 patients (86.3%) were evaluable for response at 6 to 12 months after SCT. Of these patients, 40.3% (n=219) achieved a hematologic CR. However, 18.2% (n=40) of these patients later relapsed, at a median of 3.97 years (range, 1.89-12.45).
Hematologic CR was more likely among patients who received full-dose melphalan than those who received the modified dose, occurring in 44.9% and 33.7% of patients, respectively (P=0.0091).
Relapse was more likely among patients who received melphalan at the modified dose than the full dose, occurring in 60% and 40%, respectively.
At a median follow-up of 8 years, the median OS was 7.63 years. The median OS has not been reached among patients achieving a hematologic CR, but it was 6.3 years for patients who did not achieve a hematologic CR (P<0.0001). The median OS for patients who relapsed was 4.3 years.
The median OS was significantly longer for patients who received full-dose melphalan—10.47 years, compared to 5.15 years for patients who received the modified dose (P<0.0001).
Likewise, the estimated OS rates at 1, 5, 10, and 15 years were higher for patients with a hematologic CR than for those without one. The 1-year OS is 100% and 94%, respectively. The OS at 5 years is 88% and 60%, respectively. The 10-year OS is 72% and 34%, respectively. And the OS at 15 years is 57% and 18%, respectively.
Forty patients who achieved a hematologic CR died of a cause other than relapse, including sudden death (n=7), metastatic malignancy (n=6), heart failure (n=5), renal failure (n=5), therapy-related myelodysplastic syndrome/acute myeloid leukemia (n=4), sepsis (n=4), stroke (n=3), bleeding complications (n=2), and unknown cause (n=4).
“Strategies to better understand which patients may benefit the most from this treatment and reducing treatment-related mortality, as well as using combination therapies with novel agents to increase the CR rate, will likely improve outcomes in the future for patients who, just a few years ago, were considered to have a rapidly fatal diagnosis,” Dr Sanchorawala said.
She and her colleagues also noted that this study included a “highly selected” group of new patients.
High-dose melphalan and autologous stem cell transplant (HDM/SCT) may enable long-term survival in patients with light-chain (AL) amyloidosis, according to research published in Blood.
The study included more than 500 patients who were followed for a median of 8 years, and the median overall survival (OS) was 7.63 years.
Patients tended to live longer if they had a hematologic complete response (CR) to treatment and if they received the full dose of melphalan as opposed to a modified dose.
“While survival is strongly dependent upon achieving hematologic CR, the survival of patients who did not achieve a CR and of those who relapsed after CR is notable, suggesting a benefit of aggressive treatment,” said Vaishali Sanchorawala, MD, of Boston University School of Medicine in Massachusetts.
Dr Sanchorawala and her colleagues conducted this study by analyzing data from 629 patients with AL amyloidosis who received HDM/SCT between 1994 and 2014. The patients’ median age was 57 (range, 28 to 80).
They received full-dose melphalan at 200 mg/m2 (n=350, 55.6%) or modified-dose melphalan at 100-140 mg/m2 (n=279, 44.3%), based on their age and organ function. All patients received growth factor for stem cell mobilization.
Treatment-related mortality (TRM) was defined as death within 100 days of SCT. The rate of TRM was 7.4% (n=47). Eleven deaths occurred during stem cell mobilization and collection (before melphalan was given).
After 2005, there were no deaths during stem cell mobilization and collection, and TRM improved to 3.4% (n=10).
Overall, 543 patients (86.3%) were evaluable for response at 6 to 12 months after SCT. Of these patients, 40.3% (n=219) achieved a hematologic CR. However, 18.2% (n=40) of these patients later relapsed, at a median of 3.97 years (range, 1.89-12.45).
Hematologic CR was more likely among patients who received full-dose melphalan than those who received the modified dose, occurring in 44.9% and 33.7% of patients, respectively (P=0.0091).
Relapse was more likely among patients who received melphalan at the modified dose than the full dose, occurring in 60% and 40%, respectively.
At a median follow-up of 8 years, the median OS was 7.63 years. The median OS has not been reached among patients achieving a hematologic CR, but it was 6.3 years for patients who did not achieve a hematologic CR (P<0.0001). The median OS for patients who relapsed was 4.3 years.
The median OS was significantly longer for patients who received full-dose melphalan—10.47 years, compared to 5.15 years for patients who received the modified dose (P<0.0001).
Likewise, the estimated OS rates at 1, 5, 10, and 15 years were higher for patients with a hematologic CR than for those without one. The 1-year OS is 100% and 94%, respectively. The OS at 5 years is 88% and 60%, respectively. The 10-year OS is 72% and 34%, respectively. And the OS at 15 years is 57% and 18%, respectively.
Forty patients who achieved a hematologic CR died of a cause other than relapse, including sudden death (n=7), metastatic malignancy (n=6), heart failure (n=5), renal failure (n=5), therapy-related myelodysplastic syndrome/acute myeloid leukemia (n=4), sepsis (n=4), stroke (n=3), bleeding complications (n=2), and unknown cause (n=4).
“Strategies to better understand which patients may benefit the most from this treatment and reducing treatment-related mortality, as well as using combination therapies with novel agents to increase the CR rate, will likely improve outcomes in the future for patients who, just a few years ago, were considered to have a rapidly fatal diagnosis,” Dr Sanchorawala said.
She and her colleagues also noted that this study included a “highly selected” group of new patients.
Haplo-HSCT appears comparable to fully matched HSCT
Photo by Chad McNeeley
A retrospective study suggests that, for patients with hematologic disorders, a haploidentical hematopoietic stem cell transplant (HSCT)
can be roughly as safe and effective as a fully matched HSCT.
The study showed that, when patients received an identical conditioning regimen, graft T-cell dose, and graft-vs-host disease (GVHD) prophylaxis, haploidentical and fully matched HSCTs produced comparable results.
Patients had similar rates of overall and progression-free survival, relapse, non-relapse mortality, and chronic GVHD.
However, patients who received haploidentical transplants had higher rates of grade 2-4 acute GVHD and cytomegalovirus reactivation.
Researchers reported these results in Biology of Blood and Marrow Transplantation.
“This is the first study to compare the gold standard to a half-match using an identical protocol,” said Neal Flomenberg, MD, of Thomas Jefferson University in Philadelphia, Pennsylvania.
“The field has debated whether the differences in outcomes between full and partial matches were caused by the quality of the match or by all the procedures the patient goes through before and after the donor cells are administered. We haven’t had a clear answer.”
With that in mind, Dr Flomenberg and his colleagues compared 3-year outcome data from patients who received haploidentical HSCTs (n=50) or fully matched HSCTs (n=27), when both groups of patients were treated with a 2-step protocol.
The patients had acute myeloid leukemia (n=38), acute lymphoblastic leukemia (n=20), myelodysplastic syndromes/myeloproliferative neoplasms (n=7), non-Hodgkin lymphoma (n=11), and aplastic anemia (n=1).
The 2-step protocol
All patients received a myeloablative conditioning regimen consisting of 12 Gy of total body irradiation administered in 8 fractions over 4 days. After the last fraction, they received a fixed T-cell dose (2 x 108 cells/kg), which was followed, 2 days later, by cyclophosphamide at 60 mg/kg/day for 2 days.
Twenty-four hours after they completed cyclophosphamide, patients received CD34-selected peripheral blood stem cells from a half-matched or fully matched donor.
On day -1, patients began taking tacrolimus and mycophenolate mofetil as GVHD prophylaxis. They also received growth factor support (granulocyte-macrophage colony-stimulating factor at 250 μg/m2) starting on day +1.
In the absence of GVHD, mycophenolate mofetil was discontinued on day 28 and tacrolimus was tapered, starting on day +60 after HSCT.
Results
The researchers said that early immune recovery was comparable between the patient groups in nearly all assessed T-cell subsets. The exception was the median CD3/CD8 cell count, which was significantly higher at day 28 in the fully matched group than the haploidentical group (P=0.029).
Survival rates were comparable between the groups. The estimated 3-year overall survival was 70% in the haploidentical group and 71% in the fully matched group (P=0.81). The 3-year progression-free survival was 68% and 70%, respectively (P=0.97).
The 3-year cumulative incidence of non-relapse mortality was 10% in the haploidentical group and 4% in the fully matched group (P=0.34). The 3-year cumulative incidence of relapse was 21% and 27%, respectively (P=0.93).
The 100-day cumulative incidence of grade 2-4 acute GVHD was significantly higher in the haploidentical group than the fully matched group—40% and 8%, respectively (P<0.001). But there was no significant difference in the incidence of grade 3-4 acute GVHD—6% and 4%, respectively (P=0.49).
The cumulative incidence of chronic GVHD at 2 years was not significantly different between the haploidentical and fully matched groups—19% and 12%, respectively (P=0.47). The same was true for severe chronic GVHD—4% and 8%, respectively (P=0.49).
The cumulative incidence of cytomegalovirus reactivation was significantly higher in the haploidentical group than the fully matched group—68% and 19%, respectively (P<0.001).
There were no deaths from infections or GVHD in either group.
“The results of the current study are certainly encouraging and suggest that outcomes from a half-matched, related donor are similar to fully matched donors,” said study author Sameh Gaballa, MD, also of Thomas Jefferson University.
“It might be time to reassess whether half-matched, related transplants can be considered the best alternative donor source for patients lacking a fully matched family member donor. For that, we’ll need more evidence from a randomly controlled, prospective trial, rather than studies that look at patient data retrospectively, to help solidify our findings here.”
Photo by Chad McNeeley
A retrospective study suggests that, for patients with hematologic disorders, a haploidentical hematopoietic stem cell transplant (HSCT)
can be roughly as safe and effective as a fully matched HSCT.
The study showed that, when patients received an identical conditioning regimen, graft T-cell dose, and graft-vs-host disease (GVHD) prophylaxis, haploidentical and fully matched HSCTs produced comparable results.
Patients had similar rates of overall and progression-free survival, relapse, non-relapse mortality, and chronic GVHD.
However, patients who received haploidentical transplants had higher rates of grade 2-4 acute GVHD and cytomegalovirus reactivation.
Researchers reported these results in Biology of Blood and Marrow Transplantation.
“This is the first study to compare the gold standard to a half-match using an identical protocol,” said Neal Flomenberg, MD, of Thomas Jefferson University in Philadelphia, Pennsylvania.
“The field has debated whether the differences in outcomes between full and partial matches were caused by the quality of the match or by all the procedures the patient goes through before and after the donor cells are administered. We haven’t had a clear answer.”
With that in mind, Dr Flomenberg and his colleagues compared 3-year outcome data from patients who received haploidentical HSCTs (n=50) or fully matched HSCTs (n=27), when both groups of patients were treated with a 2-step protocol.
The patients had acute myeloid leukemia (n=38), acute lymphoblastic leukemia (n=20), myelodysplastic syndromes/myeloproliferative neoplasms (n=7), non-Hodgkin lymphoma (n=11), and aplastic anemia (n=1).
The 2-step protocol
All patients received a myeloablative conditioning regimen consisting of 12 Gy of total body irradiation administered in 8 fractions over 4 days. After the last fraction, they received a fixed T-cell dose (2 x 108 cells/kg), which was followed, 2 days later, by cyclophosphamide at 60 mg/kg/day for 2 days.
Twenty-four hours after they completed cyclophosphamide, patients received CD34-selected peripheral blood stem cells from a half-matched or fully matched donor.
On day -1, patients began taking tacrolimus and mycophenolate mofetil as GVHD prophylaxis. They also received growth factor support (granulocyte-macrophage colony-stimulating factor at 250 μg/m2) starting on day +1.
In the absence of GVHD, mycophenolate mofetil was discontinued on day 28 and tacrolimus was tapered, starting on day +60 after HSCT.
Results
The researchers said that early immune recovery was comparable between the patient groups in nearly all assessed T-cell subsets. The exception was the median CD3/CD8 cell count, which was significantly higher at day 28 in the fully matched group than the haploidentical group (P=0.029).
Survival rates were comparable between the groups. The estimated 3-year overall survival was 70% in the haploidentical group and 71% in the fully matched group (P=0.81). The 3-year progression-free survival was 68% and 70%, respectively (P=0.97).
The 3-year cumulative incidence of non-relapse mortality was 10% in the haploidentical group and 4% in the fully matched group (P=0.34). The 3-year cumulative incidence of relapse was 21% and 27%, respectively (P=0.93).
The 100-day cumulative incidence of grade 2-4 acute GVHD was significantly higher in the haploidentical group than the fully matched group—40% and 8%, respectively (P<0.001). But there was no significant difference in the incidence of grade 3-4 acute GVHD—6% and 4%, respectively (P=0.49).
The cumulative incidence of chronic GVHD at 2 years was not significantly different between the haploidentical and fully matched groups—19% and 12%, respectively (P=0.47). The same was true for severe chronic GVHD—4% and 8%, respectively (P=0.49).
The cumulative incidence of cytomegalovirus reactivation was significantly higher in the haploidentical group than the fully matched group—68% and 19%, respectively (P<0.001).
There were no deaths from infections or GVHD in either group.
“The results of the current study are certainly encouraging and suggest that outcomes from a half-matched, related donor are similar to fully matched donors,” said study author Sameh Gaballa, MD, also of Thomas Jefferson University.
“It might be time to reassess whether half-matched, related transplants can be considered the best alternative donor source for patients lacking a fully matched family member donor. For that, we’ll need more evidence from a randomly controlled, prospective trial, rather than studies that look at patient data retrospectively, to help solidify our findings here.”
Photo by Chad McNeeley
A retrospective study suggests that, for patients with hematologic disorders, a haploidentical hematopoietic stem cell transplant (HSCT)
can be roughly as safe and effective as a fully matched HSCT.
The study showed that, when patients received an identical conditioning regimen, graft T-cell dose, and graft-vs-host disease (GVHD) prophylaxis, haploidentical and fully matched HSCTs produced comparable results.
Patients had similar rates of overall and progression-free survival, relapse, non-relapse mortality, and chronic GVHD.
However, patients who received haploidentical transplants had higher rates of grade 2-4 acute GVHD and cytomegalovirus reactivation.
Researchers reported these results in Biology of Blood and Marrow Transplantation.
“This is the first study to compare the gold standard to a half-match using an identical protocol,” said Neal Flomenberg, MD, of Thomas Jefferson University in Philadelphia, Pennsylvania.
“The field has debated whether the differences in outcomes between full and partial matches were caused by the quality of the match or by all the procedures the patient goes through before and after the donor cells are administered. We haven’t had a clear answer.”
With that in mind, Dr Flomenberg and his colleagues compared 3-year outcome data from patients who received haploidentical HSCTs (n=50) or fully matched HSCTs (n=27), when both groups of patients were treated with a 2-step protocol.
The patients had acute myeloid leukemia (n=38), acute lymphoblastic leukemia (n=20), myelodysplastic syndromes/myeloproliferative neoplasms (n=7), non-Hodgkin lymphoma (n=11), and aplastic anemia (n=1).
The 2-step protocol
All patients received a myeloablative conditioning regimen consisting of 12 Gy of total body irradiation administered in 8 fractions over 4 days. After the last fraction, they received a fixed T-cell dose (2 x 108 cells/kg), which was followed, 2 days later, by cyclophosphamide at 60 mg/kg/day for 2 days.
Twenty-four hours after they completed cyclophosphamide, patients received CD34-selected peripheral blood stem cells from a half-matched or fully matched donor.
On day -1, patients began taking tacrolimus and mycophenolate mofetil as GVHD prophylaxis. They also received growth factor support (granulocyte-macrophage colony-stimulating factor at 250 μg/m2) starting on day +1.
In the absence of GVHD, mycophenolate mofetil was discontinued on day 28 and tacrolimus was tapered, starting on day +60 after HSCT.
Results
The researchers said that early immune recovery was comparable between the patient groups in nearly all assessed T-cell subsets. The exception was the median CD3/CD8 cell count, which was significantly higher at day 28 in the fully matched group than the haploidentical group (P=0.029).
Survival rates were comparable between the groups. The estimated 3-year overall survival was 70% in the haploidentical group and 71% in the fully matched group (P=0.81). The 3-year progression-free survival was 68% and 70%, respectively (P=0.97).
The 3-year cumulative incidence of non-relapse mortality was 10% in the haploidentical group and 4% in the fully matched group (P=0.34). The 3-year cumulative incidence of relapse was 21% and 27%, respectively (P=0.93).
The 100-day cumulative incidence of grade 2-4 acute GVHD was significantly higher in the haploidentical group than the fully matched group—40% and 8%, respectively (P<0.001). But there was no significant difference in the incidence of grade 3-4 acute GVHD—6% and 4%, respectively (P=0.49).
The cumulative incidence of chronic GVHD at 2 years was not significantly different between the haploidentical and fully matched groups—19% and 12%, respectively (P=0.47). The same was true for severe chronic GVHD—4% and 8%, respectively (P=0.49).
The cumulative incidence of cytomegalovirus reactivation was significantly higher in the haploidentical group than the fully matched group—68% and 19%, respectively (P<0.001).
There were no deaths from infections or GVHD in either group.
“The results of the current study are certainly encouraging and suggest that outcomes from a half-matched, related donor are similar to fully matched donors,” said study author Sameh Gaballa, MD, also of Thomas Jefferson University.
“It might be time to reassess whether half-matched, related transplants can be considered the best alternative donor source for patients lacking a fully matched family member donor. For that, we’ll need more evidence from a randomly controlled, prospective trial, rather than studies that look at patient data retrospectively, to help solidify our findings here.”
Method can identify CTCL quickly, study suggests
High-throughput sequencing (HTS) may enable earlier diagnosis of cutaneous T-cell lymphoma (CTCL), according to a study published in Science Translational Medicine.
Researchers said HTS, which provided new insights into the biology of CTCL, accurately diagnosed 100% of patients with the disease, including those with early stage and recurrent CTCL.
HTS exhibited greater sensitivity and specificity than polymerase chain reaction.
The researchers noted that, in CTCL, cancerous T cells accumulate in the skin, causing skin tumors but also rashes that are often mistaken for benign inflammatory skin conditions. And this delays diagnosis.
“Using current methods, it takes, on average, 6 years for patients to receive a definitive CTCL diagnosis,” said Rachael Clark, MD, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts.
“As a result, appropriate therapy is delayed, often until the disease worsens to the point where diagnosis is clear, but effective treatment is more difficult.”
In search of a new diagnostic approach, Dr Clark and her colleagues used HTS to analyze T-cell receptor genes from blood and skin tissue samples. The team compared samples from 46 CTCL patients to samples from healthy individuals and patients with psoriasis, eczema, and other non-cancerous, inflammatory skin diseases.
By identifying and quantifying malignant T cells, HTS accurately distinguished CTCL from other skin diseases in all 46 patients. In contrast, polymerase chain reaction correctly identified 70% of the CTCL samples, often missing earlier-stage tumors.
For a subset of patients, the researchers used HTS to track malignant T cells over time, allowing them to detect early recurrence and monitor patient response to treatment.
HTS also revealed new insights into the cell of origin for CTCL, which has remained unresolved. The researchers found that CTCL arises from mature T cells, a discovery that may aid the development of more effective therapy.
The team said that, altogether, their findings suggest HTS is a promising tool for guiding earlier diagnosis and, thus, treatment of CTCL patients.
HTS was performed using ImmunoSEQ, an assay developed by Adaptive Biotechnologies. The company did not sponsor the study, but company employees were involved in the research.
High-throughput sequencing (HTS) may enable earlier diagnosis of cutaneous T-cell lymphoma (CTCL), according to a study published in Science Translational Medicine.
Researchers said HTS, which provided new insights into the biology of CTCL, accurately diagnosed 100% of patients with the disease, including those with early stage and recurrent CTCL.
HTS exhibited greater sensitivity and specificity than polymerase chain reaction.
The researchers noted that, in CTCL, cancerous T cells accumulate in the skin, causing skin tumors but also rashes that are often mistaken for benign inflammatory skin conditions. And this delays diagnosis.
“Using current methods, it takes, on average, 6 years for patients to receive a definitive CTCL diagnosis,” said Rachael Clark, MD, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts.
“As a result, appropriate therapy is delayed, often until the disease worsens to the point where diagnosis is clear, but effective treatment is more difficult.”
In search of a new diagnostic approach, Dr Clark and her colleagues used HTS to analyze T-cell receptor genes from blood and skin tissue samples. The team compared samples from 46 CTCL patients to samples from healthy individuals and patients with psoriasis, eczema, and other non-cancerous, inflammatory skin diseases.
By identifying and quantifying malignant T cells, HTS accurately distinguished CTCL from other skin diseases in all 46 patients. In contrast, polymerase chain reaction correctly identified 70% of the CTCL samples, often missing earlier-stage tumors.
For a subset of patients, the researchers used HTS to track malignant T cells over time, allowing them to detect early recurrence and monitor patient response to treatment.
HTS also revealed new insights into the cell of origin for CTCL, which has remained unresolved. The researchers found that CTCL arises from mature T cells, a discovery that may aid the development of more effective therapy.
The team said that, altogether, their findings suggest HTS is a promising tool for guiding earlier diagnosis and, thus, treatment of CTCL patients.
HTS was performed using ImmunoSEQ, an assay developed by Adaptive Biotechnologies. The company did not sponsor the study, but company employees were involved in the research.
High-throughput sequencing (HTS) may enable earlier diagnosis of cutaneous T-cell lymphoma (CTCL), according to a study published in Science Translational Medicine.
Researchers said HTS, which provided new insights into the biology of CTCL, accurately diagnosed 100% of patients with the disease, including those with early stage and recurrent CTCL.
HTS exhibited greater sensitivity and specificity than polymerase chain reaction.
The researchers noted that, in CTCL, cancerous T cells accumulate in the skin, causing skin tumors but also rashes that are often mistaken for benign inflammatory skin conditions. And this delays diagnosis.
“Using current methods, it takes, on average, 6 years for patients to receive a definitive CTCL diagnosis,” said Rachael Clark, MD, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts.
“As a result, appropriate therapy is delayed, often until the disease worsens to the point where diagnosis is clear, but effective treatment is more difficult.”
In search of a new diagnostic approach, Dr Clark and her colleagues used HTS to analyze T-cell receptor genes from blood and skin tissue samples. The team compared samples from 46 CTCL patients to samples from healthy individuals and patients with psoriasis, eczema, and other non-cancerous, inflammatory skin diseases.
By identifying and quantifying malignant T cells, HTS accurately distinguished CTCL from other skin diseases in all 46 patients. In contrast, polymerase chain reaction correctly identified 70% of the CTCL samples, often missing earlier-stage tumors.
For a subset of patients, the researchers used HTS to track malignant T cells over time, allowing them to detect early recurrence and monitor patient response to treatment.
HTS also revealed new insights into the cell of origin for CTCL, which has remained unresolved. The researchers found that CTCL arises from mature T cells, a discovery that may aid the development of more effective therapy.
The team said that, altogether, their findings suggest HTS is a promising tool for guiding earlier diagnosis and, thus, treatment of CTCL patients.
HTS was performed using ImmunoSEQ, an assay developed by Adaptive Biotechnologies. The company did not sponsor the study, but company employees were involved in the research.
Findings may inform design of new treatments for JMML
Image from the Salk Institute
Researchers have used induced pluripotent stem cells (iPSCs) to model juvenile myelomonocytic leukemia (JMML) and gain new insight into the disease.
The team noted that somatic PTPN11 mutations are known to cause JMML, germline PTPN11 defects cause Noonan syndrome (NS), and specific inherited mutations cause NS/JMML.
With their work, the researchers found that hematopoietic cells differentiated from iPSCs harboring NS/JMML-causing PTPN11 mutations recapitulate the features of JMML.
They described this work in Cell Reports.
“By studying an inherited human cancer syndrome, our study clarified early events in the development of [JMML],” said Bruce D. Gelb, MD, of the Icahn School of Medicine at Mount Sinai in New York, New York.
“More than just creating a model of a disease, we were able to prove that mechanisms seen in our model also happen in the bone marrow of people with this kind of leukemia.”
Specifically, the team found that NS/JMML myeloid cells derived from iPSCs demonstrated increased signaling through STAT5 and upregulation of 2 microRNAs—miR-223 and miR-15a.
Likewise, miR-223 and miR-15a were upregulated in 11 of 19 bone marrow samples from patients with JMML harboring PTPN11 mutations.
However, the microRNAs were not upregulated in patients without PTPN11 mutations. And when the researchers reduced miR-223’s function in NS/JMML iPSCs, they observed a normalization of myelogenesis.
“Going into the current study, experts in the field had tended to lump all forms of JMML together, but the new study was able to isolate biological changes specific to hematopoietic cells with PTPN11 mutations, which causes more severe JMML,” Dr Gelb said.
He and his colleagues also found that microRNA target gene expression levels were reduced in the iPSC-derived myeloid cells and in cells from JMML patients with PTPN11 mutations.
“Our results provide further evidence that the severity of this form of leukemia arises from the degree of changes in the gene PTPN11, altering the protein it codes for, SHP-2, and biologic pathways related to it,” Dr Gelb said. “These proteins promise to become a focus of future drug design efforts.”
Image from the Salk Institute
Researchers have used induced pluripotent stem cells (iPSCs) to model juvenile myelomonocytic leukemia (JMML) and gain new insight into the disease.
The team noted that somatic PTPN11 mutations are known to cause JMML, germline PTPN11 defects cause Noonan syndrome (NS), and specific inherited mutations cause NS/JMML.
With their work, the researchers found that hematopoietic cells differentiated from iPSCs harboring NS/JMML-causing PTPN11 mutations recapitulate the features of JMML.
They described this work in Cell Reports.
“By studying an inherited human cancer syndrome, our study clarified early events in the development of [JMML],” said Bruce D. Gelb, MD, of the Icahn School of Medicine at Mount Sinai in New York, New York.
“More than just creating a model of a disease, we were able to prove that mechanisms seen in our model also happen in the bone marrow of people with this kind of leukemia.”
Specifically, the team found that NS/JMML myeloid cells derived from iPSCs demonstrated increased signaling through STAT5 and upregulation of 2 microRNAs—miR-223 and miR-15a.
Likewise, miR-223 and miR-15a were upregulated in 11 of 19 bone marrow samples from patients with JMML harboring PTPN11 mutations.
However, the microRNAs were not upregulated in patients without PTPN11 mutations. And when the researchers reduced miR-223’s function in NS/JMML iPSCs, they observed a normalization of myelogenesis.
“Going into the current study, experts in the field had tended to lump all forms of JMML together, but the new study was able to isolate biological changes specific to hematopoietic cells with PTPN11 mutations, which causes more severe JMML,” Dr Gelb said.
He and his colleagues also found that microRNA target gene expression levels were reduced in the iPSC-derived myeloid cells and in cells from JMML patients with PTPN11 mutations.
“Our results provide further evidence that the severity of this form of leukemia arises from the degree of changes in the gene PTPN11, altering the protein it codes for, SHP-2, and biologic pathways related to it,” Dr Gelb said. “These proteins promise to become a focus of future drug design efforts.”
Image from the Salk Institute
Researchers have used induced pluripotent stem cells (iPSCs) to model juvenile myelomonocytic leukemia (JMML) and gain new insight into the disease.
The team noted that somatic PTPN11 mutations are known to cause JMML, germline PTPN11 defects cause Noonan syndrome (NS), and specific inherited mutations cause NS/JMML.
With their work, the researchers found that hematopoietic cells differentiated from iPSCs harboring NS/JMML-causing PTPN11 mutations recapitulate the features of JMML.
They described this work in Cell Reports.
“By studying an inherited human cancer syndrome, our study clarified early events in the development of [JMML],” said Bruce D. Gelb, MD, of the Icahn School of Medicine at Mount Sinai in New York, New York.
“More than just creating a model of a disease, we were able to prove that mechanisms seen in our model also happen in the bone marrow of people with this kind of leukemia.”
Specifically, the team found that NS/JMML myeloid cells derived from iPSCs demonstrated increased signaling through STAT5 and upregulation of 2 microRNAs—miR-223 and miR-15a.
Likewise, miR-223 and miR-15a were upregulated in 11 of 19 bone marrow samples from patients with JMML harboring PTPN11 mutations.
However, the microRNAs were not upregulated in patients without PTPN11 mutations. And when the researchers reduced miR-223’s function in NS/JMML iPSCs, they observed a normalization of myelogenesis.
“Going into the current study, experts in the field had tended to lump all forms of JMML together, but the new study was able to isolate biological changes specific to hematopoietic cells with PTPN11 mutations, which causes more severe JMML,” Dr Gelb said.
He and his colleagues also found that microRNA target gene expression levels were reduced in the iPSC-derived myeloid cells and in cells from JMML patients with PTPN11 mutations.
“Our results provide further evidence that the severity of this form of leukemia arises from the degree of changes in the gene PTPN11, altering the protein it codes for, SHP-2, and biologic pathways related to it,” Dr Gelb said. “These proteins promise to become a focus of future drug design efforts.”
Smartphone use may put patient data at risk
Photo by Daniel Sone
A new survey suggests that doctors and nurses in London are routinely using their own smartphones for patient care.
Investigators say the current lack of data encryption on these devices could result in the inadvertent disclosure of “highly sensitive and confidential data” in the absence of an active organizational strategy on digital security.
The team raised this issue and reported results of the survey in BMJ Innovations.
Mohammad H. Mobasheri, MBBS, of Imperial College London in the UK, and his colleagues wanted to determine how healthcare professionals are using digital technology on the frontline.
So the investigators invited more than 6000 clinical staff at 5 London hospitals of varying sizes to complete a questionnaire on ownership and use of portable devices and mobile health apps in the workplace.
The results are based on the responses of 287 doctors and 564 nurses from different specialties.
About 99% of doctors said they owned a smartphone, and 73.5% owned a tablet. The equivalent figures for nurses were 95.1% and 64.7%, respectively.
When asked about the usefulness of smartphones for carrying out clinical duties, 92.6% of doctors and 53.2% of nurses said these devices were “very useful” or “useful.”
Most doctors (93.8%) used their smartphone while at work to communicate with their colleagues, compared with 28.5% of nurses. About half of the doctors (50.2%) used their smartphone instead of a traditional bleep (page).
About 78% of doctors and 34.8% of nurses said they had downloaded a medical app to their device, with 89.6% of doctors and 67.1% of nurses saying they used these apps as part of their clinical work.
Of those who owned a medical app and used it at work, 41.3% of doctors reported using such an app weekly, and 33% said they used one daily. The equivalent figures for nurses were 42% and 22.3%, respectively.
The apps included drug formularies, medical calculators, and those for disease diagnosis and treatment, reference and education, documentation and drug preparation.
When asked if they had ever sent patient data over their smartphones using SMS, app-based messaging (such as WhatsApp), and picture messaging using their smartphone camera, many respondents said they had done so.
About 65% of doctors had used SMS, 33.1% had used app-based messaging, and 46% had used their phone’s camera and picture messaging to send a photo of a wound or X-ray to a colleague. The corresponding figures for nurses were much lower—13.8%, 5.7%, and 7.4%, respectively.
About 28% of doctors and 3.6% of nurses said they still retained clinical information on their smartphones.
A substantial proportion of respondents said they wanted to be able to use their own devices at work. About 72% of doctors and 37.2% of nurses wanted a secure means of sending patient data to colleagues using their own smartphone.
Fully secure messaging services for smartphones are not yet available in the UK, and the data are unlikely to be encrypted, according to investigators. They therefore urged National Health Service organizations to make sure their staff understands the potential risks of sharing patient information via their unsecured smartphones.
The team said the results of this survey provide strong evidence that healthcare organizations need to develop policies to support the safe and secure use of digital technologies in the workplace.
Photo by Daniel Sone
A new survey suggests that doctors and nurses in London are routinely using their own smartphones for patient care.
Investigators say the current lack of data encryption on these devices could result in the inadvertent disclosure of “highly sensitive and confidential data” in the absence of an active organizational strategy on digital security.
The team raised this issue and reported results of the survey in BMJ Innovations.
Mohammad H. Mobasheri, MBBS, of Imperial College London in the UK, and his colleagues wanted to determine how healthcare professionals are using digital technology on the frontline.
So the investigators invited more than 6000 clinical staff at 5 London hospitals of varying sizes to complete a questionnaire on ownership and use of portable devices and mobile health apps in the workplace.
The results are based on the responses of 287 doctors and 564 nurses from different specialties.
About 99% of doctors said they owned a smartphone, and 73.5% owned a tablet. The equivalent figures for nurses were 95.1% and 64.7%, respectively.
When asked about the usefulness of smartphones for carrying out clinical duties, 92.6% of doctors and 53.2% of nurses said these devices were “very useful” or “useful.”
Most doctors (93.8%) used their smartphone while at work to communicate with their colleagues, compared with 28.5% of nurses. About half of the doctors (50.2%) used their smartphone instead of a traditional bleep (page).
About 78% of doctors and 34.8% of nurses said they had downloaded a medical app to their device, with 89.6% of doctors and 67.1% of nurses saying they used these apps as part of their clinical work.
Of those who owned a medical app and used it at work, 41.3% of doctors reported using such an app weekly, and 33% said they used one daily. The equivalent figures for nurses were 42% and 22.3%, respectively.
The apps included drug formularies, medical calculators, and those for disease diagnosis and treatment, reference and education, documentation and drug preparation.
When asked if they had ever sent patient data over their smartphones using SMS, app-based messaging (such as WhatsApp), and picture messaging using their smartphone camera, many respondents said they had done so.
About 65% of doctors had used SMS, 33.1% had used app-based messaging, and 46% had used their phone’s camera and picture messaging to send a photo of a wound or X-ray to a colleague. The corresponding figures for nurses were much lower—13.8%, 5.7%, and 7.4%, respectively.
About 28% of doctors and 3.6% of nurses said they still retained clinical information on their smartphones.
A substantial proportion of respondents said they wanted to be able to use their own devices at work. About 72% of doctors and 37.2% of nurses wanted a secure means of sending patient data to colleagues using their own smartphone.
Fully secure messaging services for smartphones are not yet available in the UK, and the data are unlikely to be encrypted, according to investigators. They therefore urged National Health Service organizations to make sure their staff understands the potential risks of sharing patient information via their unsecured smartphones.
The team said the results of this survey provide strong evidence that healthcare organizations need to develop policies to support the safe and secure use of digital technologies in the workplace.
Photo by Daniel Sone
A new survey suggests that doctors and nurses in London are routinely using their own smartphones for patient care.
Investigators say the current lack of data encryption on these devices could result in the inadvertent disclosure of “highly sensitive and confidential data” in the absence of an active organizational strategy on digital security.
The team raised this issue and reported results of the survey in BMJ Innovations.
Mohammad H. Mobasheri, MBBS, of Imperial College London in the UK, and his colleagues wanted to determine how healthcare professionals are using digital technology on the frontline.
So the investigators invited more than 6000 clinical staff at 5 London hospitals of varying sizes to complete a questionnaire on ownership and use of portable devices and mobile health apps in the workplace.
The results are based on the responses of 287 doctors and 564 nurses from different specialties.
About 99% of doctors said they owned a smartphone, and 73.5% owned a tablet. The equivalent figures for nurses were 95.1% and 64.7%, respectively.
When asked about the usefulness of smartphones for carrying out clinical duties, 92.6% of doctors and 53.2% of nurses said these devices were “very useful” or “useful.”
Most doctors (93.8%) used their smartphone while at work to communicate with their colleagues, compared with 28.5% of nurses. About half of the doctors (50.2%) used their smartphone instead of a traditional bleep (page).
About 78% of doctors and 34.8% of nurses said they had downloaded a medical app to their device, with 89.6% of doctors and 67.1% of nurses saying they used these apps as part of their clinical work.
Of those who owned a medical app and used it at work, 41.3% of doctors reported using such an app weekly, and 33% said they used one daily. The equivalent figures for nurses were 42% and 22.3%, respectively.
The apps included drug formularies, medical calculators, and those for disease diagnosis and treatment, reference and education, documentation and drug preparation.
When asked if they had ever sent patient data over their smartphones using SMS, app-based messaging (such as WhatsApp), and picture messaging using their smartphone camera, many respondents said they had done so.
About 65% of doctors had used SMS, 33.1% had used app-based messaging, and 46% had used their phone’s camera and picture messaging to send a photo of a wound or X-ray to a colleague. The corresponding figures for nurses were much lower—13.8%, 5.7%, and 7.4%, respectively.
About 28% of doctors and 3.6% of nurses said they still retained clinical information on their smartphones.
A substantial proportion of respondents said they wanted to be able to use their own devices at work. About 72% of doctors and 37.2% of nurses wanted a secure means of sending patient data to colleagues using their own smartphone.
Fully secure messaging services for smartphones are not yet available in the UK, and the data are unlikely to be encrypted, according to investigators. They therefore urged National Health Service organizations to make sure their staff understands the potential risks of sharing patient information via their unsecured smartphones.
The team said the results of this survey provide strong evidence that healthcare organizations need to develop policies to support the safe and secure use of digital technologies in the workplace.
JAK inhibitors could treat Sézary syndrome, team says
Photo courtesy of NIGMS
Patients with Sézary syndrome (SS) may have a more complex array of genetic mutations than we thought, according to a paper published in Nature Communications.
Investigators uncovered a genomic landscape that, they believe, can be used to design personalized treatment regimens for SS patients.
In particular, the team found mutations in the JAK/STAT pathway and discovered that JAK-mutated SS cells are sensitive to JAK inhibitors.
To conduct this research, the investigators sequenced SS patient samples using 3 different approaches. They performed whole-genome sequencing (n=6), whole-exome sequencing (n=66), and array comparative genomic hybridization-based copy-number analysis (n=80).
“We basically found chromosomal chaos in all of our samples,” said study author Kojo Elenitoba-Johnson, MD, of the University of Pennsylvania in Philadelphia.
“We did not expect the degree of genetic complexity that we found in our study.”
The investigators identified previously unknown, recurrent, loss-of-function mutations that target genes regulating epigenetic pathways.
One of these targets is ARID1A, and the team found that loss-of-function mutations and/or deletions in ARID1A occurred in more than 40% of the SS genome studied.
The investigators also identified gain-of-function mutations in PLCG1, JAK1, JAK3, STAT3, and STAT5B.
And in preliminary drug-mutation matching studies, JAK1-mutated SS cells were sensitive to JAK inhibitors.
“With knowledge like this, we can design clinical trials using JAK inhibitors for SS patients based on their JAK mutations,” Dr Elenitoba-Johnson said. “But this is just the start. These results highlight the genetic vulnerabilities that we can use in designing precision medicine therapies.”
Now, the investigators want to develop a molecular taxonomy for mutations in SS patients. Using the sequencing technology they used in this study, the team hopes to pinpoint the exact mistakes in each patient’s SS-related genes.
From this, the investigators hope to identify distinct subsets of the disease and stratify patients for precision therapy based on their mutations and the inhibitors available for those mutations.
Photo courtesy of NIGMS
Patients with Sézary syndrome (SS) may have a more complex array of genetic mutations than we thought, according to a paper published in Nature Communications.
Investigators uncovered a genomic landscape that, they believe, can be used to design personalized treatment regimens for SS patients.
In particular, the team found mutations in the JAK/STAT pathway and discovered that JAK-mutated SS cells are sensitive to JAK inhibitors.
To conduct this research, the investigators sequenced SS patient samples using 3 different approaches. They performed whole-genome sequencing (n=6), whole-exome sequencing (n=66), and array comparative genomic hybridization-based copy-number analysis (n=80).
“We basically found chromosomal chaos in all of our samples,” said study author Kojo Elenitoba-Johnson, MD, of the University of Pennsylvania in Philadelphia.
“We did not expect the degree of genetic complexity that we found in our study.”
The investigators identified previously unknown, recurrent, loss-of-function mutations that target genes regulating epigenetic pathways.
One of these targets is ARID1A, and the team found that loss-of-function mutations and/or deletions in ARID1A occurred in more than 40% of the SS genome studied.
The investigators also identified gain-of-function mutations in PLCG1, JAK1, JAK3, STAT3, and STAT5B.
And in preliminary drug-mutation matching studies, JAK1-mutated SS cells were sensitive to JAK inhibitors.
“With knowledge like this, we can design clinical trials using JAK inhibitors for SS patients based on their JAK mutations,” Dr Elenitoba-Johnson said. “But this is just the start. These results highlight the genetic vulnerabilities that we can use in designing precision medicine therapies.”
Now, the investigators want to develop a molecular taxonomy for mutations in SS patients. Using the sequencing technology they used in this study, the team hopes to pinpoint the exact mistakes in each patient’s SS-related genes.
From this, the investigators hope to identify distinct subsets of the disease and stratify patients for precision therapy based on their mutations and the inhibitors available for those mutations.
Photo courtesy of NIGMS
Patients with Sézary syndrome (SS) may have a more complex array of genetic mutations than we thought, according to a paper published in Nature Communications.
Investigators uncovered a genomic landscape that, they believe, can be used to design personalized treatment regimens for SS patients.
In particular, the team found mutations in the JAK/STAT pathway and discovered that JAK-mutated SS cells are sensitive to JAK inhibitors.
To conduct this research, the investigators sequenced SS patient samples using 3 different approaches. They performed whole-genome sequencing (n=6), whole-exome sequencing (n=66), and array comparative genomic hybridization-based copy-number analysis (n=80).
“We basically found chromosomal chaos in all of our samples,” said study author Kojo Elenitoba-Johnson, MD, of the University of Pennsylvania in Philadelphia.
“We did not expect the degree of genetic complexity that we found in our study.”
The investigators identified previously unknown, recurrent, loss-of-function mutations that target genes regulating epigenetic pathways.
One of these targets is ARID1A, and the team found that loss-of-function mutations and/or deletions in ARID1A occurred in more than 40% of the SS genome studied.
The investigators also identified gain-of-function mutations in PLCG1, JAK1, JAK3, STAT3, and STAT5B.
And in preliminary drug-mutation matching studies, JAK1-mutated SS cells were sensitive to JAK inhibitors.
“With knowledge like this, we can design clinical trials using JAK inhibitors for SS patients based on their JAK mutations,” Dr Elenitoba-Johnson said. “But this is just the start. These results highlight the genetic vulnerabilities that we can use in designing precision medicine therapies.”
Now, the investigators want to develop a molecular taxonomy for mutations in SS patients. Using the sequencing technology they used in this study, the team hopes to pinpoint the exact mistakes in each patient’s SS-related genes.
From this, the investigators hope to identify distinct subsets of the disease and stratify patients for precision therapy based on their mutations and the inhibitors available for those mutations.