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New radiation guidelines for pediatric HL
New guidelines on radiation therapy aim to help physicians more effectively treat pediatric Hodgkin lymphoma (HL) while reducing the radiation dose to normal tissue.
Previous guidelines for pediatric HL have focused on 2D imaging and bony landmarks to define dose volumes for radiation therapy, and they’ve recommended treating large volumes of normal tissue, in part, because of uncertainty about which lymph node areas were involved.
The new guidelines, published in Practical Radiation Oncology, describe how to use modern imaging and advances in radiation therapy planning technology to treat patients with pediatric HL while decreasing the risk of late side effects, including second cancers and heart disease.
The authors describe methods for identifying target volumes for radiation therapy and how to implement the concept of involved-site radiation to define radiation target volumes and limit the dose to normal organs at risk.
According to the guidelines, accurate assessment of the extent and location of disease requires both contrast-enhanced CT as well as FDG-PET.
The document describes how the evaluation of response to chemotherapy influences the targeting of the lymphoma and the volume of normal tissue treated, by fusing CT and FDG-PET images taken before and after chemotherapy to CT imaging taken for radiation therapy planning.
“The emergence of new imaging technologies, more accurate ways of delivering radiation therapy, and more detailed patient selection criteria have made a significant change in our ability to customize treatment for many cancer patients,” said lead guideline author David C. Hodgson, MD, of the University of Toronto in Ontario, Canada.
“This guideline has the potential to reduce the radiation therapy breast dose by about 80% and the heart dose by about 65% for an adolescent girl with Hodgkin lymphoma. This shift in more personalized treatment planning tailored to the individual patient’s disease will optimize risk-benefit considerations for our patients and reduce the likelihood that they will suffer late effects from radiation therapy.” 
New guidelines on radiation therapy aim to help physicians more effectively treat pediatric Hodgkin lymphoma (HL) while reducing the radiation dose to normal tissue.
Previous guidelines for pediatric HL have focused on 2D imaging and bony landmarks to define dose volumes for radiation therapy, and they’ve recommended treating large volumes of normal tissue, in part, because of uncertainty about which lymph node areas were involved.
The new guidelines, published in Practical Radiation Oncology, describe how to use modern imaging and advances in radiation therapy planning technology to treat patients with pediatric HL while decreasing the risk of late side effects, including second cancers and heart disease.
The authors describe methods for identifying target volumes for radiation therapy and how to implement the concept of involved-site radiation to define radiation target volumes and limit the dose to normal organs at risk.
According to the guidelines, accurate assessment of the extent and location of disease requires both contrast-enhanced CT as well as FDG-PET.
The document describes how the evaluation of response to chemotherapy influences the targeting of the lymphoma and the volume of normal tissue treated, by fusing CT and FDG-PET images taken before and after chemotherapy to CT imaging taken for radiation therapy planning.
“The emergence of new imaging technologies, more accurate ways of delivering radiation therapy, and more detailed patient selection criteria have made a significant change in our ability to customize treatment for many cancer patients,” said lead guideline author David C. Hodgson, MD, of the University of Toronto in Ontario, Canada.
“This guideline has the potential to reduce the radiation therapy breast dose by about 80% and the heart dose by about 65% for an adolescent girl with Hodgkin lymphoma. This shift in more personalized treatment planning tailored to the individual patient’s disease will optimize risk-benefit considerations for our patients and reduce the likelihood that they will suffer late effects from radiation therapy.”
New guidelines on radiation therapy aim to help physicians more effectively treat pediatric Hodgkin lymphoma (HL) while reducing the radiation dose to normal tissue.
Previous guidelines for pediatric HL have focused on 2D imaging and bony landmarks to define dose volumes for radiation therapy, and they’ve recommended treating large volumes of normal tissue, in part, because of uncertainty about which lymph node areas were involved.
The new guidelines, published in Practical Radiation Oncology, describe how to use modern imaging and advances in radiation therapy planning technology to treat patients with pediatric HL while decreasing the risk of late side effects, including second cancers and heart disease.
The authors describe methods for identifying target volumes for radiation therapy and how to implement the concept of involved-site radiation to define radiation target volumes and limit the dose to normal organs at risk.
According to the guidelines, accurate assessment of the extent and location of disease requires both contrast-enhanced CT as well as FDG-PET.
The document describes how the evaluation of response to chemotherapy influences the targeting of the lymphoma and the volume of normal tissue treated, by fusing CT and FDG-PET images taken before and after chemotherapy to CT imaging taken for radiation therapy planning.
“The emergence of new imaging technologies, more accurate ways of delivering radiation therapy, and more detailed patient selection criteria have made a significant change in our ability to customize treatment for many cancer patients,” said lead guideline author David C. Hodgson, MD, of the University of Toronto in Ontario, Canada.
“This guideline has the potential to reduce the radiation therapy breast dose by about 80% and the heart dose by about 65% for an adolescent girl with Hodgkin lymphoma. This shift in more personalized treatment planning tailored to the individual patient’s disease will optimize risk-benefit considerations for our patients and reduce the likelihood that they will suffer late effects from radiation therapy.”
Parasite discovery could aid malaria treatment
Image by Ke Hu & John Murray
Researchers say they have gained new insight into how malaria-related parasites spread inside humans and other animals.
The team discovered how the malaria relative Toxoplasma gondii manages to replicate its chromosomes up to thousands of times before spinning off into daughter cells—all while avoiding cell death.
The findings, published in PLOS Biology, may have implications for malaria treatment, according to the researchers.
Once transmitted into an animal or human, malaria-related parasites can hide out in a single cell in many different tissues, replicating thousands of times before the host’s immune system can detect them.
Then, they burst forth as daughter cells, which are unleashed in massive quantities, quickly overwhelming the body’s immune response.
The researchers found that Toxoplasma parasites pull this off thanks to the centrosome, which imposes order on the replication chaos.
“Unlike the comparatively simple centrosome present in human cells, the parasite [centrosome] has 2 distinct operating machines,” said study author Michael White, PhD, of the University of South Florida in Tampa.
“One machine controls chromosome copying, while the other machine regulates when to form daughter cell bodies. Working together, but with independent responsibilities, parasite centrosome machines can dictate the scale and timing of pathogen replication.”
This discovery of the centrosome’s function leads to a critical conclusion, Dr White said. Disrupting the centrosome machines kills the parasite. Breaking any part of the highly efficient but highly fragile replication function shuts everything down.
With these findings and the new knowledge of the parasites’ vulnerabilities, Dr White and his fellow researchers are planning to explore drug development for malaria. Whether the team is able to find an already-approved drug or must develop one from scratch, they said the drug will need to be used in conjunction with other therapies.
Dr White noted that current drugs used to treat malaria target the pathogen’s metabolism. But the goal of the new drug will be to undermine the parasite’s foundation in enough of the spreading cells to allow the immune system to fight back and not become overwhelmed.
Image by Ke Hu & John Murray
Researchers say they have gained new insight into how malaria-related parasites spread inside humans and other animals.
The team discovered how the malaria relative Toxoplasma gondii manages to replicate its chromosomes up to thousands of times before spinning off into daughter cells—all while avoiding cell death.
The findings, published in PLOS Biology, may have implications for malaria treatment, according to the researchers.
Once transmitted into an animal or human, malaria-related parasites can hide out in a single cell in many different tissues, replicating thousands of times before the host’s immune system can detect them.
Then, they burst forth as daughter cells, which are unleashed in massive quantities, quickly overwhelming the body’s immune response.
The researchers found that Toxoplasma parasites pull this off thanks to the centrosome, which imposes order on the replication chaos.
“Unlike the comparatively simple centrosome present in human cells, the parasite [centrosome] has 2 distinct operating machines,” said study author Michael White, PhD, of the University of South Florida in Tampa.
“One machine controls chromosome copying, while the other machine regulates when to form daughter cell bodies. Working together, but with independent responsibilities, parasite centrosome machines can dictate the scale and timing of pathogen replication.”
This discovery of the centrosome’s function leads to a critical conclusion, Dr White said. Disrupting the centrosome machines kills the parasite. Breaking any part of the highly efficient but highly fragile replication function shuts everything down.
With these findings and the new knowledge of the parasites’ vulnerabilities, Dr White and his fellow researchers are planning to explore drug development for malaria. Whether the team is able to find an already-approved drug or must develop one from scratch, they said the drug will need to be used in conjunction with other therapies.
Dr White noted that current drugs used to treat malaria target the pathogen’s metabolism. But the goal of the new drug will be to undermine the parasite’s foundation in enough of the spreading cells to allow the immune system to fight back and not become overwhelmed.
Image by Ke Hu & John Murray
Researchers say they have gained new insight into how malaria-related parasites spread inside humans and other animals.
The team discovered how the malaria relative Toxoplasma gondii manages to replicate its chromosomes up to thousands of times before spinning off into daughter cells—all while avoiding cell death.
The findings, published in PLOS Biology, may have implications for malaria treatment, according to the researchers.
Once transmitted into an animal or human, malaria-related parasites can hide out in a single cell in many different tissues, replicating thousands of times before the host’s immune system can detect them.
Then, they burst forth as daughter cells, which are unleashed in massive quantities, quickly overwhelming the body’s immune response.
The researchers found that Toxoplasma parasites pull this off thanks to the centrosome, which imposes order on the replication chaos.
“Unlike the comparatively simple centrosome present in human cells, the parasite [centrosome] has 2 distinct operating machines,” said study author Michael White, PhD, of the University of South Florida in Tampa.
“One machine controls chromosome copying, while the other machine regulates when to form daughter cell bodies. Working together, but with independent responsibilities, parasite centrosome machines can dictate the scale and timing of pathogen replication.”
This discovery of the centrosome’s function leads to a critical conclusion, Dr White said. Disrupting the centrosome machines kills the parasite. Breaking any part of the highly efficient but highly fragile replication function shuts everything down.
With these findings and the new knowledge of the parasites’ vulnerabilities, Dr White and his fellow researchers are planning to explore drug development for malaria. Whether the team is able to find an already-approved drug or must develop one from scratch, they said the drug will need to be used in conjunction with other therapies.
Dr White noted that current drugs used to treat malaria target the pathogen’s metabolism. But the goal of the new drug will be to undermine the parasite’s foundation in enough of the spreading cells to allow the immune system to fight back and not become overwhelmed.
Cancer care spending doesn’t correlate to lives saved
Photo by Rhoda Baer
A new analysis suggests that although US spending on cancer treatment has increased greatly in recent years, cancer mortality rates have decreased only modestly.
The study showed that care in the US often failed to prevent cancer-related deaths as well as care in Western Europe.
And when deaths were averted in the US, there was a substantial cost attached, said study author Samir Soneji, PhD, of the Norris Cotton Cancer Center in Lebanon, New Hampshire.
He and JaeWon Yang, a former undergraduate at Dartmouth College in Hanover, New Hampshire, reported these findings in Health Affairs.
The researchers compared cancer deaths and money spent on cancer care in the US and Western Europe between 1982 and 2010. They found that costs were higher in the US than in Europe for all cancers analyzed.
And compared to Western Europe, the US had 64,560 excess leukemia deaths; 164,429 excess non-Hodgkin lymphoma (NHL) deaths; 1,119,599 excess lung cancer deaths; and 39,144 excess melanoma deaths.
On the other hand, the US averted 4859 Hodgkin lymphoma deaths; 66,797 breast cancer deaths; 4354 cervical/uterine cancer deaths; 264,632 colorectal cancer deaths; 59,882 prostate cancer deaths; 621,820 stomach cancer deaths; 3372 testicular cancer deaths; and 18,320 thyroid cancer deaths.
“The greatest number of deaths averted occurred in cancers for which decreasing mortality rates were more likely to be the result of successful prevention and screening rather than advancements in treatment,” Dr Soneji noted.
He and Yang also found that the ratio of incremental cost to quality-adjusted life years (QALYs) saved in the US was $156,045 for Hodgkin lymphoma; $402,369 for breast cancer; $110,009 for colorectal cancer; $1,978,542 for prostate cancer; $4635 for stomach cancer; $222,839 for testicular cancer; and $139,681 for thyroid cancer.
But the US lost QALYs despite additional spending for leukemia, NHL, and a few other cancers. The incremental cost divided by QALYs saved was -$30,790 for leukemia; -$41,362 for NHL; -$855,019 for cervical/uterine cancer; -$18,815 for lung cancer, and -$136,592 for melanoma.
Dr Soneji described these results as, “substantially contrary to previous findings, especially for breast and prostate cancer, despite using the same data” as a previous study published in Health Affairs.
Non-replicability is a serious problem throughout academia, Dr Soneji noted. So to promote open discussion, he makes his data and procedures available to all scholars on an open-access repository called Dataverse.
Photo by Rhoda Baer
A new analysis suggests that although US spending on cancer treatment has increased greatly in recent years, cancer mortality rates have decreased only modestly.
The study showed that care in the US often failed to prevent cancer-related deaths as well as care in Western Europe.
And when deaths were averted in the US, there was a substantial cost attached, said study author Samir Soneji, PhD, of the Norris Cotton Cancer Center in Lebanon, New Hampshire.
He and JaeWon Yang, a former undergraduate at Dartmouth College in Hanover, New Hampshire, reported these findings in Health Affairs.
The researchers compared cancer deaths and money spent on cancer care in the US and Western Europe between 1982 and 2010. They found that costs were higher in the US than in Europe for all cancers analyzed.
And compared to Western Europe, the US had 64,560 excess leukemia deaths; 164,429 excess non-Hodgkin lymphoma (NHL) deaths; 1,119,599 excess lung cancer deaths; and 39,144 excess melanoma deaths.
On the other hand, the US averted 4859 Hodgkin lymphoma deaths; 66,797 breast cancer deaths; 4354 cervical/uterine cancer deaths; 264,632 colorectal cancer deaths; 59,882 prostate cancer deaths; 621,820 stomach cancer deaths; 3372 testicular cancer deaths; and 18,320 thyroid cancer deaths.
“The greatest number of deaths averted occurred in cancers for which decreasing mortality rates were more likely to be the result of successful prevention and screening rather than advancements in treatment,” Dr Soneji noted.
He and Yang also found that the ratio of incremental cost to quality-adjusted life years (QALYs) saved in the US was $156,045 for Hodgkin lymphoma; $402,369 for breast cancer; $110,009 for colorectal cancer; $1,978,542 for prostate cancer; $4635 for stomach cancer; $222,839 for testicular cancer; and $139,681 for thyroid cancer.
But the US lost QALYs despite additional spending for leukemia, NHL, and a few other cancers. The incremental cost divided by QALYs saved was -$30,790 for leukemia; -$41,362 for NHL; -$855,019 for cervical/uterine cancer; -$18,815 for lung cancer, and -$136,592 for melanoma.
Dr Soneji described these results as, “substantially contrary to previous findings, especially for breast and prostate cancer, despite using the same data” as a previous study published in Health Affairs.
Non-replicability is a serious problem throughout academia, Dr Soneji noted. So to promote open discussion, he makes his data and procedures available to all scholars on an open-access repository called Dataverse.
Photo by Rhoda Baer
A new analysis suggests that although US spending on cancer treatment has increased greatly in recent years, cancer mortality rates have decreased only modestly.
The study showed that care in the US often failed to prevent cancer-related deaths as well as care in Western Europe.
And when deaths were averted in the US, there was a substantial cost attached, said study author Samir Soneji, PhD, of the Norris Cotton Cancer Center in Lebanon, New Hampshire.
He and JaeWon Yang, a former undergraduate at Dartmouth College in Hanover, New Hampshire, reported these findings in Health Affairs.
The researchers compared cancer deaths and money spent on cancer care in the US and Western Europe between 1982 and 2010. They found that costs were higher in the US than in Europe for all cancers analyzed.
And compared to Western Europe, the US had 64,560 excess leukemia deaths; 164,429 excess non-Hodgkin lymphoma (NHL) deaths; 1,119,599 excess lung cancer deaths; and 39,144 excess melanoma deaths.
On the other hand, the US averted 4859 Hodgkin lymphoma deaths; 66,797 breast cancer deaths; 4354 cervical/uterine cancer deaths; 264,632 colorectal cancer deaths; 59,882 prostate cancer deaths; 621,820 stomach cancer deaths; 3372 testicular cancer deaths; and 18,320 thyroid cancer deaths.
“The greatest number of deaths averted occurred in cancers for which decreasing mortality rates were more likely to be the result of successful prevention and screening rather than advancements in treatment,” Dr Soneji noted.
He and Yang also found that the ratio of incremental cost to quality-adjusted life years (QALYs) saved in the US was $156,045 for Hodgkin lymphoma; $402,369 for breast cancer; $110,009 for colorectal cancer; $1,978,542 for prostate cancer; $4635 for stomach cancer; $222,839 for testicular cancer; and $139,681 for thyroid cancer.
But the US lost QALYs despite additional spending for leukemia, NHL, and a few other cancers. The incremental cost divided by QALYs saved was -$30,790 for leukemia; -$41,362 for NHL; -$855,019 for cervical/uterine cancer; -$18,815 for lung cancer, and -$136,592 for melanoma.
Dr Soneji described these results as, “substantially contrary to previous findings, especially for breast and prostate cancer, despite using the same data” as a previous study published in Health Affairs.
Non-replicability is a serious problem throughout academia, Dr Soneji noted. So to promote open discussion, he makes his data and procedures available to all scholars on an open-access repository called Dataverse.
Drug shows promise for treating VOD after HSCT
Photo by Chad McNeeley
SAN DIEGO—Results of 3 studies appear to support the use of defibrotide in patients who develop hepatic veno-occlusive disease (VOD) after hematopoietic stem cell transplant (HSCT).
Defibrotide is the sodium salt of a complex mixture of single-stranded oligodeoxyribonucleotides derived from porcine mucosal DNA. It has antithrombotic, anti-inflammatory, and anti-ischemic properties.
The drug is already approved in Europe to treat VOD and is under investigation for this indication in the US.
Researchers presented data from 3 studies showing promising results with defibrotide at the 2015 BMT Tandem Meetings. The studies were sponsored by Jazz Pharmaceuticals, the company developing defibrotide.
T-IND study
Paul G. Richardson, MD, of the Dana-Farber Cancer Institute in Boston, presented data from an ongoing treatment investigational new drug (T-IND) study (abstract 111*).
The study included 641 patients with VOD who received at least one dose of defibrotide—279 who had severe VOD with multi-organ failure (MOF), 247 who had VOD without MOF, and 526 who had undergone HSCT.
Twenty-one percent of patients had at least 1 treatment-related adverse event (AE). Common treatment-related AEs included hypotension (13%), respiratory failure (8%), diarrhea (8%), pyrexia (7%), pulmonary hemorrhage (7%), renal failure (7%), vomiting (6%), gastrointestinal hemorrhage (6%), hypoxia (6%), epistaxis (5%), and nausea (5%).
At day 100 in post-HSCT patients, the overall survival rate was 52%. The rate was 45% among patients with MOF, and 60% among patients without MOF.
Dr Richardson concluded that defibrotide was generally well-tolerated, and the survival results were favorable. He noted that the higher survival rate in patients without MOF indicates a need to study the impact of treatment earlier in the course of VOD.
NNT study
Dr Richardson also presented data from a number needed to treat (NNT) analysis from a historically controlled, phase 3 trial in patients undergoing HSCT (abstract 112).
For this study, researchers used data from the phase 3 trial to evaluate the NNT with defibrotide to achieve 1 complete response (CR) or to prevent 1 death at day 100 after HSCT in patients with severe VOD (n=102) compared with untreated, historical controls (n=32).
At 100 days, 23.5% of patients in the defibrotide cohort had a CR, compared to 9.4% of historical controls (P=0.013). Survival at 100 days was 38.2% in the defibrotide cohort and 25% among historical controls (P=0.034).
Based on these data, the NNT to achieve 1 CR with defibrotide by day 100 was 7, and the NNT to prevent 1 death at day 100 was 8.
Dr Richardson concluded that defibrotide demonstrated improved CR and survival in patients with severe VOD. And the NNTs with defibrotide are comparable to or lower than those with other therapeutic medical interventions in critical care.
Compassionate use program
Selim Corbacioglu, MD, of the University of Regensburg in Germany, presented final results of an international compassionate use program for defibrotide (abstract 109).
The program included 710 patients who received at least 1 documented dose of defibrotide. In all, 628 patients had undergone HSCT, 429 had severe VOD, and 292 had MOF.
Twenty-eight percent of patients discontinued treatment with defibrotide. Fifty-three percent of patients had AEs, 18% of which were possibly treatment-related. These were primarily gastrointestinal hemorrhage (2%), hemorrhage (1%), and pulmonary hemorrhage (1%).
At day 100 (post-HSCT, chemotherapy, or radiation), the survival rate was 54%. Survival varied according to defibrotide dose. It was 43% for the 10 mg/kg/day group, 58% for the 25 mg/kg/day group, 54% for the 40 mg/kg/day group, 61% for the 60/80 mg/kg/day group, and 51% for patients whose dose was unknown.
Dr Corbacioglu noted that the side-effect profile and the survival rates in this program were consistent with those observed in prior defibrotide studies. And these data support 25 mg/kg/day as the optimal dose of the drug.
*Information in the abstract differs from that presented at the meeting.
Photo by Chad McNeeley
SAN DIEGO—Results of 3 studies appear to support the use of defibrotide in patients who develop hepatic veno-occlusive disease (VOD) after hematopoietic stem cell transplant (HSCT).
Defibrotide is the sodium salt of a complex mixture of single-stranded oligodeoxyribonucleotides derived from porcine mucosal DNA. It has antithrombotic, anti-inflammatory, and anti-ischemic properties.
The drug is already approved in Europe to treat VOD and is under investigation for this indication in the US.
Researchers presented data from 3 studies showing promising results with defibrotide at the 2015 BMT Tandem Meetings. The studies were sponsored by Jazz Pharmaceuticals, the company developing defibrotide.
T-IND study
Paul G. Richardson, MD, of the Dana-Farber Cancer Institute in Boston, presented data from an ongoing treatment investigational new drug (T-IND) study (abstract 111*).
The study included 641 patients with VOD who received at least one dose of defibrotide—279 who had severe VOD with multi-organ failure (MOF), 247 who had VOD without MOF, and 526 who had undergone HSCT.
Twenty-one percent of patients had at least 1 treatment-related adverse event (AE). Common treatment-related AEs included hypotension (13%), respiratory failure (8%), diarrhea (8%), pyrexia (7%), pulmonary hemorrhage (7%), renal failure (7%), vomiting (6%), gastrointestinal hemorrhage (6%), hypoxia (6%), epistaxis (5%), and nausea (5%).
At day 100 in post-HSCT patients, the overall survival rate was 52%. The rate was 45% among patients with MOF, and 60% among patients without MOF.
Dr Richardson concluded that defibrotide was generally well-tolerated, and the survival results were favorable. He noted that the higher survival rate in patients without MOF indicates a need to study the impact of treatment earlier in the course of VOD.
NNT study
Dr Richardson also presented data from a number needed to treat (NNT) analysis from a historically controlled, phase 3 trial in patients undergoing HSCT (abstract 112).
For this study, researchers used data from the phase 3 trial to evaluate the NNT with defibrotide to achieve 1 complete response (CR) or to prevent 1 death at day 100 after HSCT in patients with severe VOD (n=102) compared with untreated, historical controls (n=32).
At 100 days, 23.5% of patients in the defibrotide cohort had a CR, compared to 9.4% of historical controls (P=0.013). Survival at 100 days was 38.2% in the defibrotide cohort and 25% among historical controls (P=0.034).
Based on these data, the NNT to achieve 1 CR with defibrotide by day 100 was 7, and the NNT to prevent 1 death at day 100 was 8.
Dr Richardson concluded that defibrotide demonstrated improved CR and survival in patients with severe VOD. And the NNTs with defibrotide are comparable to or lower than those with other therapeutic medical interventions in critical care.
Compassionate use program
Selim Corbacioglu, MD, of the University of Regensburg in Germany, presented final results of an international compassionate use program for defibrotide (abstract 109).
The program included 710 patients who received at least 1 documented dose of defibrotide. In all, 628 patients had undergone HSCT, 429 had severe VOD, and 292 had MOF.
Twenty-eight percent of patients discontinued treatment with defibrotide. Fifty-three percent of patients had AEs, 18% of which were possibly treatment-related. These were primarily gastrointestinal hemorrhage (2%), hemorrhage (1%), and pulmonary hemorrhage (1%).
At day 100 (post-HSCT, chemotherapy, or radiation), the survival rate was 54%. Survival varied according to defibrotide dose. It was 43% for the 10 mg/kg/day group, 58% for the 25 mg/kg/day group, 54% for the 40 mg/kg/day group, 61% for the 60/80 mg/kg/day group, and 51% for patients whose dose was unknown.
Dr Corbacioglu noted that the side-effect profile and the survival rates in this program were consistent with those observed in prior defibrotide studies. And these data support 25 mg/kg/day as the optimal dose of the drug.
*Information in the abstract differs from that presented at the meeting.
Photo by Chad McNeeley
SAN DIEGO—Results of 3 studies appear to support the use of defibrotide in patients who develop hepatic veno-occlusive disease (VOD) after hematopoietic stem cell transplant (HSCT).
Defibrotide is the sodium salt of a complex mixture of single-stranded oligodeoxyribonucleotides derived from porcine mucosal DNA. It has antithrombotic, anti-inflammatory, and anti-ischemic properties.
The drug is already approved in Europe to treat VOD and is under investigation for this indication in the US.
Researchers presented data from 3 studies showing promising results with defibrotide at the 2015 BMT Tandem Meetings. The studies were sponsored by Jazz Pharmaceuticals, the company developing defibrotide.
T-IND study
Paul G. Richardson, MD, of the Dana-Farber Cancer Institute in Boston, presented data from an ongoing treatment investigational new drug (T-IND) study (abstract 111*).
The study included 641 patients with VOD who received at least one dose of defibrotide—279 who had severe VOD with multi-organ failure (MOF), 247 who had VOD without MOF, and 526 who had undergone HSCT.
Twenty-one percent of patients had at least 1 treatment-related adverse event (AE). Common treatment-related AEs included hypotension (13%), respiratory failure (8%), diarrhea (8%), pyrexia (7%), pulmonary hemorrhage (7%), renal failure (7%), vomiting (6%), gastrointestinal hemorrhage (6%), hypoxia (6%), epistaxis (5%), and nausea (5%).
At day 100 in post-HSCT patients, the overall survival rate was 52%. The rate was 45% among patients with MOF, and 60% among patients without MOF.
Dr Richardson concluded that defibrotide was generally well-tolerated, and the survival results were favorable. He noted that the higher survival rate in patients without MOF indicates a need to study the impact of treatment earlier in the course of VOD.
NNT study
Dr Richardson also presented data from a number needed to treat (NNT) analysis from a historically controlled, phase 3 trial in patients undergoing HSCT (abstract 112).
For this study, researchers used data from the phase 3 trial to evaluate the NNT with defibrotide to achieve 1 complete response (CR) or to prevent 1 death at day 100 after HSCT in patients with severe VOD (n=102) compared with untreated, historical controls (n=32).
At 100 days, 23.5% of patients in the defibrotide cohort had a CR, compared to 9.4% of historical controls (P=0.013). Survival at 100 days was 38.2% in the defibrotide cohort and 25% among historical controls (P=0.034).
Based on these data, the NNT to achieve 1 CR with defibrotide by day 100 was 7, and the NNT to prevent 1 death at day 100 was 8.
Dr Richardson concluded that defibrotide demonstrated improved CR and survival in patients with severe VOD. And the NNTs with defibrotide are comparable to or lower than those with other therapeutic medical interventions in critical care.
Compassionate use program
Selim Corbacioglu, MD, of the University of Regensburg in Germany, presented final results of an international compassionate use program for defibrotide (abstract 109).
The program included 710 patients who received at least 1 documented dose of defibrotide. In all, 628 patients had undergone HSCT, 429 had severe VOD, and 292 had MOF.
Twenty-eight percent of patients discontinued treatment with defibrotide. Fifty-three percent of patients had AEs, 18% of which were possibly treatment-related. These were primarily gastrointestinal hemorrhage (2%), hemorrhage (1%), and pulmonary hemorrhage (1%).
At day 100 (post-HSCT, chemotherapy, or radiation), the survival rate was 54%. Survival varied according to defibrotide dose. It was 43% for the 10 mg/kg/day group, 58% for the 25 mg/kg/day group, 54% for the 40 mg/kg/day group, 61% for the 60/80 mg/kg/day group, and 51% for patients whose dose was unknown.
Dr Corbacioglu noted that the side-effect profile and the survival rates in this program were consistent with those observed in prior defibrotide studies. And these data support 25 mg/kg/day as the optimal dose of the drug.
*Information in the abstract differs from that presented at the meeting.
Combo can fight resistant lymphoma
Photo by Aaron Logan
Combining the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib with an anti-PD-L1 antibody can override resistance to ibrutinib, according to preclinical research.
Investigators found the combination of anti-PD-L1 and ibrutinib suppressed tumor growth in mouse models of lymphoma that are intrinsically insensitive to ibrutinib.
The combination also proved effective against 2 solid tumor malignancies—triple-negative breast cancer and colon cancer.
Ronald Levy, MD, of the Stanford University School of Medicine in California, and his colleagues described this work in PNAS.
The team first studied A20, a B-cell lymphoma in BALB/c mice that is insensitive to ibrutinib treatment even though A20 cells express BTK.
A20 cells also express high levels of PD-L1, so it follows that some of the mice responded to anti-PD-L1 treatment alone. However, the response eventually diminished over time.
When the investigators administered ibrutinib along with anti-PD-L1, half of the mice were cured. The other half experienced delays in tumor growth and prolonged survival.
Dr Levy and his colleagues also assessed ibrutinib plus anti-PD-L1 in 2 solid tumor models. They chose triple-negative breast cancer and colon cancer, which do not express BTK and have low levels of the PD-L1 protein.
When ibrutinib and the PD-L1 antibody were given as single agents, neither had any effect on tumor growth. However, combination treatment reduced the size of the primary tumors, improved survival, and resulted in fewer metastases in both breast and colon cancer.
In the case of the colon cancer model, approximately 30% of the mice were cured. The investigators decided to test whether these mice had developed long-term immune memory from the treatment.
So the team re-exposed the mice to colon cancer cells at 90 days post-cure. After 7 days of tumor growth, all the mice cleared the tumor by day 17 without any additional dosing of the ibrutinib and anti-PD-L1 combination.
“These findings are very encouraging and support our pursuit of a clinical development strategy that combines ibrutinib with anti-PD-L1 antibodies or other checkpoint inhibitors to maximize the effect that both drugs could have in treating cancer,” said Darrin Beaupre, MD, PhD, of Pharmacyclics, the company developing ibrutinib, which contributed funding for this research.
“Based on what we’ve seen preclinically, we are optimistic that combinations such as these may help to produce new treatment paradigms for patients with cancer.”
The investigators did not draw any conclusions about the safety of anti-PD-L1 and ibrutinib in combination.
They did note that both agents have been well-tolerated when given alone, but additional study of the combination is needed to fully understand the appropriate dosing, timing, and sequencing of combination treatment.
Investigators are planning clinical studies testing ibrutinib in combination with the anti-PD-L1 immune checkpoint inhibitor MEDI4736 (in hematologic and solid tumor malignancies) and with the PD-1-blocking antibody nivolumab (in hematologic malignancies). Enrollment is expected to begin in the coming months.
Photo by Aaron Logan
Combining the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib with an anti-PD-L1 antibody can override resistance to ibrutinib, according to preclinical research.
Investigators found the combination of anti-PD-L1 and ibrutinib suppressed tumor growth in mouse models of lymphoma that are intrinsically insensitive to ibrutinib.
The combination also proved effective against 2 solid tumor malignancies—triple-negative breast cancer and colon cancer.
Ronald Levy, MD, of the Stanford University School of Medicine in California, and his colleagues described this work in PNAS.
The team first studied A20, a B-cell lymphoma in BALB/c mice that is insensitive to ibrutinib treatment even though A20 cells express BTK.
A20 cells also express high levels of PD-L1, so it follows that some of the mice responded to anti-PD-L1 treatment alone. However, the response eventually diminished over time.
When the investigators administered ibrutinib along with anti-PD-L1, half of the mice were cured. The other half experienced delays in tumor growth and prolonged survival.
Dr Levy and his colleagues also assessed ibrutinib plus anti-PD-L1 in 2 solid tumor models. They chose triple-negative breast cancer and colon cancer, which do not express BTK and have low levels of the PD-L1 protein.
When ibrutinib and the PD-L1 antibody were given as single agents, neither had any effect on tumor growth. However, combination treatment reduced the size of the primary tumors, improved survival, and resulted in fewer metastases in both breast and colon cancer.
In the case of the colon cancer model, approximately 30% of the mice were cured. The investigators decided to test whether these mice had developed long-term immune memory from the treatment.
So the team re-exposed the mice to colon cancer cells at 90 days post-cure. After 7 days of tumor growth, all the mice cleared the tumor by day 17 without any additional dosing of the ibrutinib and anti-PD-L1 combination.
“These findings are very encouraging and support our pursuit of a clinical development strategy that combines ibrutinib with anti-PD-L1 antibodies or other checkpoint inhibitors to maximize the effect that both drugs could have in treating cancer,” said Darrin Beaupre, MD, PhD, of Pharmacyclics, the company developing ibrutinib, which contributed funding for this research.
“Based on what we’ve seen preclinically, we are optimistic that combinations such as these may help to produce new treatment paradigms for patients with cancer.”
The investigators did not draw any conclusions about the safety of anti-PD-L1 and ibrutinib in combination.
They did note that both agents have been well-tolerated when given alone, but additional study of the combination is needed to fully understand the appropriate dosing, timing, and sequencing of combination treatment.
Investigators are planning clinical studies testing ibrutinib in combination with the anti-PD-L1 immune checkpoint inhibitor MEDI4736 (in hematologic and solid tumor malignancies) and with the PD-1-blocking antibody nivolumab (in hematologic malignancies). Enrollment is expected to begin in the coming months.
Photo by Aaron Logan
Combining the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib with an anti-PD-L1 antibody can override resistance to ibrutinib, according to preclinical research.
Investigators found the combination of anti-PD-L1 and ibrutinib suppressed tumor growth in mouse models of lymphoma that are intrinsically insensitive to ibrutinib.
The combination also proved effective against 2 solid tumor malignancies—triple-negative breast cancer and colon cancer.
Ronald Levy, MD, of the Stanford University School of Medicine in California, and his colleagues described this work in PNAS.
The team first studied A20, a B-cell lymphoma in BALB/c mice that is insensitive to ibrutinib treatment even though A20 cells express BTK.
A20 cells also express high levels of PD-L1, so it follows that some of the mice responded to anti-PD-L1 treatment alone. However, the response eventually diminished over time.
When the investigators administered ibrutinib along with anti-PD-L1, half of the mice were cured. The other half experienced delays in tumor growth and prolonged survival.
Dr Levy and his colleagues also assessed ibrutinib plus anti-PD-L1 in 2 solid tumor models. They chose triple-negative breast cancer and colon cancer, which do not express BTK and have low levels of the PD-L1 protein.
When ibrutinib and the PD-L1 antibody were given as single agents, neither had any effect on tumor growth. However, combination treatment reduced the size of the primary tumors, improved survival, and resulted in fewer metastases in both breast and colon cancer.
In the case of the colon cancer model, approximately 30% of the mice were cured. The investigators decided to test whether these mice had developed long-term immune memory from the treatment.
So the team re-exposed the mice to colon cancer cells at 90 days post-cure. After 7 days of tumor growth, all the mice cleared the tumor by day 17 without any additional dosing of the ibrutinib and anti-PD-L1 combination.
“These findings are very encouraging and support our pursuit of a clinical development strategy that combines ibrutinib with anti-PD-L1 antibodies or other checkpoint inhibitors to maximize the effect that both drugs could have in treating cancer,” said Darrin Beaupre, MD, PhD, of Pharmacyclics, the company developing ibrutinib, which contributed funding for this research.
“Based on what we’ve seen preclinically, we are optimistic that combinations such as these may help to produce new treatment paradigms for patients with cancer.”
The investigators did not draw any conclusions about the safety of anti-PD-L1 and ibrutinib in combination.
They did note that both agents have been well-tolerated when given alone, but additional study of the combination is needed to fully understand the appropriate dosing, timing, and sequencing of combination treatment.
Investigators are planning clinical studies testing ibrutinib in combination with the anti-PD-L1 immune checkpoint inhibitor MEDI4736 (in hematologic and solid tumor malignancies) and with the PD-1-blocking antibody nivolumab (in hematologic malignancies). Enrollment is expected to begin in the coming months.
Agent decreases use of pain meds in SCD patients
and a normal one
Image by Betty Pace
An investigational agent may be able to treat vaso-occlusive crises (VOC) in patients with sickle cell disease (SCD), according to research published in Blood.
The drug, rivipansel (formerly GMI-1070), is designed to prevent cells from sticking together to improve blood flow.
In a phase 2 study, SCD patients who received rivipansel used significantly less pain medication than those who received placebo.
However, rivipansel did not significantly reduce the time to resolution of VOC.
Researchers said the study’s small size, as well as the wide variability in the length of time that all patients suffered painful vascular obstruction, may explain the lack of statistical significance. A larger, international study is set to begin later this year to provide greater clarity.
“We have not had good therapies for people with [sickle cell] disease,” said study author Marilyn J. Telen, MD, of Duke University in Durham, North Carolina.
“But this approach shows more promise than anything else I’ve seen in 34 years of treating sickle cell disease.”
She and her colleagues analyzed 76 SCD patients from 17 sites in the US. The patients were randomized to receive placebo or rivipansel. All patients also received the standard treatment for pain and symptom management.
For patients who received rivipansel, the effects tended to begin within 24 hours, and their painful crises passed sooner than those receiving only treatment for pain, but the statistical difference was not significant.
The least-squares mean time to resolution of VOC was 103.64 hours in the rivipansel arm and 144.60 hours in the placebo arm (P=0.192). The median times were 69.6 hours and 132.9 hours, respectively (P=0.187).
The researchers said the improvements seen in the amount of time to resolution would likely be clinically meaningful if they were verified in a larger trial.
The team also said the findings demonstrating lower use of pain medication among patients was a critical step forward. The team assessed cumulative parenteral opioid use, and the least-squares mean dose was 9.62 mg/kg in the rivipansel arm and 55.59 mg/kg in the placebo arm (P=0.010).
“The difference in pain medication use was statistically significant, and it occurred in the first 24 hours, which implies that the therapy may be interfering with the mechanism of the vaso-occlusion,” Dr Telen said. “For these patients, having less pain is very important.”
In addition, there were no significant differences between the treatment arms with regard to adverse events.
Dr Telen said the larger study of rivipansel is set to begin later this year, with a goal of enrolling more than 300 patients.
The company developing rivipansel, GlycoMimetics, Inc., funded the current study. And Dr Telen has received consulting fees from the company.
and a normal one
Image by Betty Pace
An investigational agent may be able to treat vaso-occlusive crises (VOC) in patients with sickle cell disease (SCD), according to research published in Blood.
The drug, rivipansel (formerly GMI-1070), is designed to prevent cells from sticking together to improve blood flow.
In a phase 2 study, SCD patients who received rivipansel used significantly less pain medication than those who received placebo.
However, rivipansel did not significantly reduce the time to resolution of VOC.
Researchers said the study’s small size, as well as the wide variability in the length of time that all patients suffered painful vascular obstruction, may explain the lack of statistical significance. A larger, international study is set to begin later this year to provide greater clarity.
“We have not had good therapies for people with [sickle cell] disease,” said study author Marilyn J. Telen, MD, of Duke University in Durham, North Carolina.
“But this approach shows more promise than anything else I’ve seen in 34 years of treating sickle cell disease.”
She and her colleagues analyzed 76 SCD patients from 17 sites in the US. The patients were randomized to receive placebo or rivipansel. All patients also received the standard treatment for pain and symptom management.
For patients who received rivipansel, the effects tended to begin within 24 hours, and their painful crises passed sooner than those receiving only treatment for pain, but the statistical difference was not significant.
The least-squares mean time to resolution of VOC was 103.64 hours in the rivipansel arm and 144.60 hours in the placebo arm (P=0.192). The median times were 69.6 hours and 132.9 hours, respectively (P=0.187).
The researchers said the improvements seen in the amount of time to resolution would likely be clinically meaningful if they were verified in a larger trial.
The team also said the findings demonstrating lower use of pain medication among patients was a critical step forward. The team assessed cumulative parenteral opioid use, and the least-squares mean dose was 9.62 mg/kg in the rivipansel arm and 55.59 mg/kg in the placebo arm (P=0.010).
“The difference in pain medication use was statistically significant, and it occurred in the first 24 hours, which implies that the therapy may be interfering with the mechanism of the vaso-occlusion,” Dr Telen said. “For these patients, having less pain is very important.”
In addition, there were no significant differences between the treatment arms with regard to adverse events.
Dr Telen said the larger study of rivipansel is set to begin later this year, with a goal of enrolling more than 300 patients.
The company developing rivipansel, GlycoMimetics, Inc., funded the current study. And Dr Telen has received consulting fees from the company.
and a normal one
Image by Betty Pace
An investigational agent may be able to treat vaso-occlusive crises (VOC) in patients with sickle cell disease (SCD), according to research published in Blood.
The drug, rivipansel (formerly GMI-1070), is designed to prevent cells from sticking together to improve blood flow.
In a phase 2 study, SCD patients who received rivipansel used significantly less pain medication than those who received placebo.
However, rivipansel did not significantly reduce the time to resolution of VOC.
Researchers said the study’s small size, as well as the wide variability in the length of time that all patients suffered painful vascular obstruction, may explain the lack of statistical significance. A larger, international study is set to begin later this year to provide greater clarity.
“We have not had good therapies for people with [sickle cell] disease,” said study author Marilyn J. Telen, MD, of Duke University in Durham, North Carolina.
“But this approach shows more promise than anything else I’ve seen in 34 years of treating sickle cell disease.”
She and her colleagues analyzed 76 SCD patients from 17 sites in the US. The patients were randomized to receive placebo or rivipansel. All patients also received the standard treatment for pain and symptom management.
For patients who received rivipansel, the effects tended to begin within 24 hours, and their painful crises passed sooner than those receiving only treatment for pain, but the statistical difference was not significant.
The least-squares mean time to resolution of VOC was 103.64 hours in the rivipansel arm and 144.60 hours in the placebo arm (P=0.192). The median times were 69.6 hours and 132.9 hours, respectively (P=0.187).
The researchers said the improvements seen in the amount of time to resolution would likely be clinically meaningful if they were verified in a larger trial.
The team also said the findings demonstrating lower use of pain medication among patients was a critical step forward. The team assessed cumulative parenteral opioid use, and the least-squares mean dose was 9.62 mg/kg in the rivipansel arm and 55.59 mg/kg in the placebo arm (P=0.010).
“The difference in pain medication use was statistically significant, and it occurred in the first 24 hours, which implies that the therapy may be interfering with the mechanism of the vaso-occlusion,” Dr Telen said. “For these patients, having less pain is very important.”
In addition, there were no significant differences between the treatment arms with regard to adverse events.
Dr Telen said the larger study of rivipansel is set to begin later this year, with a goal of enrolling more than 300 patients.
The company developing rivipansel, GlycoMimetics, Inc., funded the current study. And Dr Telen has received consulting fees from the company.
Too many blood tests can lead to anemia, transfusions
Photo by Juan D. Alfonso
A single-center study has shown that laboratory testing among patients undergoing cardiac surgery can lead to excessive bloodletting.
This can increase the risk of hospital-acquired anemia and, therefore, the need for blood transfusions.
Among cardiac surgery patients, transfusions have been associated with an increased risk of infection, more time spent on a ventilator, and a higher likelihood of death, said Colleen G. Koch, MD, of the Cleveland Clinic in Ohio.
She and her colleagues conducted this research and published their findings in The Annals of Thoracic Surgery.
The researchers recorded every laboratory test performed on 1894 patients who underwent cardiac surgery at the Cleveland Clinic from January to June 2012.
The team evaluated the number and type of blood tests performed from the time patients met their surgeons until hospital discharge, tallying up the total amount of blood taken from each patient.
‘Astonishing’ amount of blood drawn
There were 221,498 laboratory tests performed during the study period, or an average of 115 tests per patient. The most common tests were blood gas analyses (n=88,068), coagulation tests (n=39,535), complete blood counts (n=30,421), and metabolic panels (n=29,374).
The cumulative median phlebotomy volume for the entire hospital stay was 454 mL per patient. Patients tended to have more blood drawn if they were in the intensive care unit as compared to other hospital floors, with median phlebotomy volumes of 332 mL and 118 mL, respectively.
“We were astonished by the amount of blood taken from our patients for laboratory testing,” Dr Koch said. “Total phlebotomy volumes approached 1 to 2 units of red blood cells, which is roughly equivalent to 1 to 2 cans of soda.”
More complex procedures were associated with higher overall phlebotomy volume. Patients undergoing combined coronary artery bypass grafting surgery (CABG) and valve procedures had the highest median cumulative phlebotomy volume. The median volume was 653 mL for CABG-valve procedures, 448 mL for CABG alone, and 338 mL for valve procedures alone.
Transfusion need
The researchers also found that an increase in cumulative phlebotomy volume was linked to an increased need for blood products. Similarly, the longer a patient was hospitalized, the more blood was taken, which increased the subsequent need for a transfusion.
Overall, 49% of patients received red blood cells (RBCs), 25% fresh-frozen plasma (FFP), 33% platelets, and 15% cryoprecipitate.
Patients in the lowest phlebotomy volume quartile (0%-25th%) were much less likely to receive transfusions than patients in the highest quartile (75th% to 100th%).
In the lowest quartile, 2% of patients received cryoprecipitate, 3% FFP, 7% platelets, and 12% RBCs. In the highest quartile, 31% of patients received cryoprecipitate, 54% FFP, 61% platelets, and 87% RBCs.
So to reduce the use of transfusions, we must curb the use of blood tests, Dr Koch said, noting that patients can help.
“Patients should feel empowered to ask their doctors whether a specific test is necessary—’What is the indication for the test?,’ ‘Will it change my care?,’ and ‘If so, do you need to do it every day?,’” Dr Koch said.
“They should inquire whether smaller-volume test tubes could be used for the tests that are deemed necessary. Every attempt should be made to conserve the patient’s own blood. Every drop of blood counts.”
In an invited commentary, Milo Engoren, MD, of the University of Michigan in Ann Arbor, emphasized the importance of reducing blood loss to decrease possible complications during surgery.
“We make efforts to minimize intraoperative blood loss,” he noted. “Now, we need to make similar efforts postoperatively. While some may argue that transfusion itself is not harmful, but only a marker of a sicker patient, most would agree that avoiding anemia and transfusion is the best course for patients.”
Photo by Juan D. Alfonso
A single-center study has shown that laboratory testing among patients undergoing cardiac surgery can lead to excessive bloodletting.
This can increase the risk of hospital-acquired anemia and, therefore, the need for blood transfusions.
Among cardiac surgery patients, transfusions have been associated with an increased risk of infection, more time spent on a ventilator, and a higher likelihood of death, said Colleen G. Koch, MD, of the Cleveland Clinic in Ohio.
She and her colleagues conducted this research and published their findings in The Annals of Thoracic Surgery.
The researchers recorded every laboratory test performed on 1894 patients who underwent cardiac surgery at the Cleveland Clinic from January to June 2012.
The team evaluated the number and type of blood tests performed from the time patients met their surgeons until hospital discharge, tallying up the total amount of blood taken from each patient.
‘Astonishing’ amount of blood drawn
There were 221,498 laboratory tests performed during the study period, or an average of 115 tests per patient. The most common tests were blood gas analyses (n=88,068), coagulation tests (n=39,535), complete blood counts (n=30,421), and metabolic panels (n=29,374).
The cumulative median phlebotomy volume for the entire hospital stay was 454 mL per patient. Patients tended to have more blood drawn if they were in the intensive care unit as compared to other hospital floors, with median phlebotomy volumes of 332 mL and 118 mL, respectively.
“We were astonished by the amount of blood taken from our patients for laboratory testing,” Dr Koch said. “Total phlebotomy volumes approached 1 to 2 units of red blood cells, which is roughly equivalent to 1 to 2 cans of soda.”
More complex procedures were associated with higher overall phlebotomy volume. Patients undergoing combined coronary artery bypass grafting surgery (CABG) and valve procedures had the highest median cumulative phlebotomy volume. The median volume was 653 mL for CABG-valve procedures, 448 mL for CABG alone, and 338 mL for valve procedures alone.
Transfusion need
The researchers also found that an increase in cumulative phlebotomy volume was linked to an increased need for blood products. Similarly, the longer a patient was hospitalized, the more blood was taken, which increased the subsequent need for a transfusion.
Overall, 49% of patients received red blood cells (RBCs), 25% fresh-frozen plasma (FFP), 33% platelets, and 15% cryoprecipitate.
Patients in the lowest phlebotomy volume quartile (0%-25th%) were much less likely to receive transfusions than patients in the highest quartile (75th% to 100th%).
In the lowest quartile, 2% of patients received cryoprecipitate, 3% FFP, 7% platelets, and 12% RBCs. In the highest quartile, 31% of patients received cryoprecipitate, 54% FFP, 61% platelets, and 87% RBCs.
So to reduce the use of transfusions, we must curb the use of blood tests, Dr Koch said, noting that patients can help.
“Patients should feel empowered to ask their doctors whether a specific test is necessary—’What is the indication for the test?,’ ‘Will it change my care?,’ and ‘If so, do you need to do it every day?,’” Dr Koch said.
“They should inquire whether smaller-volume test tubes could be used for the tests that are deemed necessary. Every attempt should be made to conserve the patient’s own blood. Every drop of blood counts.”
In an invited commentary, Milo Engoren, MD, of the University of Michigan in Ann Arbor, emphasized the importance of reducing blood loss to decrease possible complications during surgery.
“We make efforts to minimize intraoperative blood loss,” he noted. “Now, we need to make similar efforts postoperatively. While some may argue that transfusion itself is not harmful, but only a marker of a sicker patient, most would agree that avoiding anemia and transfusion is the best course for patients.”
Photo by Juan D. Alfonso
A single-center study has shown that laboratory testing among patients undergoing cardiac surgery can lead to excessive bloodletting.
This can increase the risk of hospital-acquired anemia and, therefore, the need for blood transfusions.
Among cardiac surgery patients, transfusions have been associated with an increased risk of infection, more time spent on a ventilator, and a higher likelihood of death, said Colleen G. Koch, MD, of the Cleveland Clinic in Ohio.
She and her colleagues conducted this research and published their findings in The Annals of Thoracic Surgery.
The researchers recorded every laboratory test performed on 1894 patients who underwent cardiac surgery at the Cleveland Clinic from January to June 2012.
The team evaluated the number and type of blood tests performed from the time patients met their surgeons until hospital discharge, tallying up the total amount of blood taken from each patient.
‘Astonishing’ amount of blood drawn
There were 221,498 laboratory tests performed during the study period, or an average of 115 tests per patient. The most common tests were blood gas analyses (n=88,068), coagulation tests (n=39,535), complete blood counts (n=30,421), and metabolic panels (n=29,374).
The cumulative median phlebotomy volume for the entire hospital stay was 454 mL per patient. Patients tended to have more blood drawn if they were in the intensive care unit as compared to other hospital floors, with median phlebotomy volumes of 332 mL and 118 mL, respectively.
“We were astonished by the amount of blood taken from our patients for laboratory testing,” Dr Koch said. “Total phlebotomy volumes approached 1 to 2 units of red blood cells, which is roughly equivalent to 1 to 2 cans of soda.”
More complex procedures were associated with higher overall phlebotomy volume. Patients undergoing combined coronary artery bypass grafting surgery (CABG) and valve procedures had the highest median cumulative phlebotomy volume. The median volume was 653 mL for CABG-valve procedures, 448 mL for CABG alone, and 338 mL for valve procedures alone.
Transfusion need
The researchers also found that an increase in cumulative phlebotomy volume was linked to an increased need for blood products. Similarly, the longer a patient was hospitalized, the more blood was taken, which increased the subsequent need for a transfusion.
Overall, 49% of patients received red blood cells (RBCs), 25% fresh-frozen plasma (FFP), 33% platelets, and 15% cryoprecipitate.
Patients in the lowest phlebotomy volume quartile (0%-25th%) were much less likely to receive transfusions than patients in the highest quartile (75th% to 100th%).
In the lowest quartile, 2% of patients received cryoprecipitate, 3% FFP, 7% platelets, and 12% RBCs. In the highest quartile, 31% of patients received cryoprecipitate, 54% FFP, 61% platelets, and 87% RBCs.
So to reduce the use of transfusions, we must curb the use of blood tests, Dr Koch said, noting that patients can help.
“Patients should feel empowered to ask their doctors whether a specific test is necessary—’What is the indication for the test?,’ ‘Will it change my care?,’ and ‘If so, do you need to do it every day?,’” Dr Koch said.
“They should inquire whether smaller-volume test tubes could be used for the tests that are deemed necessary. Every attempt should be made to conserve the patient’s own blood. Every drop of blood counts.”
In an invited commentary, Milo Engoren, MD, of the University of Michigan in Ann Arbor, emphasized the importance of reducing blood loss to decrease possible complications during surgery.
“We make efforts to minimize intraoperative blood loss,” he noted. “Now, we need to make similar efforts postoperatively. While some may argue that transfusion itself is not harmful, but only a marker of a sicker patient, most would agree that avoiding anemia and transfusion is the best course for patients.”
FDA grants T-cell therapy breakthrough designation
Photo by Charles Haymond
The US Food and Drug Administration (FDA) has granted breakthrough designation to a therapy consisting of cytotoxic T lymphocytes activated against Epstein-Barr virus (EBV-CTLs).
The treatment is intended for use in patients with rituximab-refractory, EBV-associated lymphoproliferative disease (EBV-LPD), which occurs after allogeneic hematopoietic stem cell transplant.
EBV-CTLs consist of T cells collected from third-party donors.
The T cells are exposed to antigens, expanded, characterized, and stored for future use in an appropriate, partially HLA-matched patient.
In the context of EBV-LPD, the EBV-CTLs are able to target and destroy cancer cells expressing EBV.
“The receipt of breakthrough therapy designation brings us one step closer to our ultimate goal of making EBV-CTL available to all patients with EBV-LPD, a serious and life-threatening condition with limited treatment options,” said Richard O’Reilly, MD, Chair of the Department of Pediatrics and Chief of the Pediatric Bone Marrow Transplant Service at Memorial Sloan Kettering Cancer Center (MSKCC) in New York, New York.
MSKCC is developing EBV-CTLs in conjunction with Atara Biotherapeutics, Inc.
Breakthrough therapy designation for EBV-CTLs was based on data from 2 clinical trials of EBV-CTLs conducted at MSKCC.
Data from these studies have been submitted for presentation at an upcoming medical conference. Results of a phase 1/2 study of EBV-CTLs were previously presented at the APHON 37th Annual Conference and Exhibit in 2013.
The FDA’s breakthrough therapy designation is designed to expedite the development and review of new drugs for the treatment of serious or life-threatening conditions.
To qualify for this designation, a drug must show credible evidence of a substantial improvement on a clinically significant endpoint over available therapies, or over placebo if there is no available therapy, or in a study that compares the new treatment plus the standard of care to the standard of care alone.
The designation confers several benefits, including intensive FDA guidance and eligibility for submission of a rolling biologic license application.
Photo by Charles Haymond
The US Food and Drug Administration (FDA) has granted breakthrough designation to a therapy consisting of cytotoxic T lymphocytes activated against Epstein-Barr virus (EBV-CTLs).
The treatment is intended for use in patients with rituximab-refractory, EBV-associated lymphoproliferative disease (EBV-LPD), which occurs after allogeneic hematopoietic stem cell transplant.
EBV-CTLs consist of T cells collected from third-party donors.
The T cells are exposed to antigens, expanded, characterized, and stored for future use in an appropriate, partially HLA-matched patient.
In the context of EBV-LPD, the EBV-CTLs are able to target and destroy cancer cells expressing EBV.
“The receipt of breakthrough therapy designation brings us one step closer to our ultimate goal of making EBV-CTL available to all patients with EBV-LPD, a serious and life-threatening condition with limited treatment options,” said Richard O’Reilly, MD, Chair of the Department of Pediatrics and Chief of the Pediatric Bone Marrow Transplant Service at Memorial Sloan Kettering Cancer Center (MSKCC) in New York, New York.
MSKCC is developing EBV-CTLs in conjunction with Atara Biotherapeutics, Inc.
Breakthrough therapy designation for EBV-CTLs was based on data from 2 clinical trials of EBV-CTLs conducted at MSKCC.
Data from these studies have been submitted for presentation at an upcoming medical conference. Results of a phase 1/2 study of EBV-CTLs were previously presented at the APHON 37th Annual Conference and Exhibit in 2013.
The FDA’s breakthrough therapy designation is designed to expedite the development and review of new drugs for the treatment of serious or life-threatening conditions.
To qualify for this designation, a drug must show credible evidence of a substantial improvement on a clinically significant endpoint over available therapies, or over placebo if there is no available therapy, or in a study that compares the new treatment plus the standard of care to the standard of care alone.
The designation confers several benefits, including intensive FDA guidance and eligibility for submission of a rolling biologic license application.
Photo by Charles Haymond
The US Food and Drug Administration (FDA) has granted breakthrough designation to a therapy consisting of cytotoxic T lymphocytes activated against Epstein-Barr virus (EBV-CTLs).
The treatment is intended for use in patients with rituximab-refractory, EBV-associated lymphoproliferative disease (EBV-LPD), which occurs after allogeneic hematopoietic stem cell transplant.
EBV-CTLs consist of T cells collected from third-party donors.
The T cells are exposed to antigens, expanded, characterized, and stored for future use in an appropriate, partially HLA-matched patient.
In the context of EBV-LPD, the EBV-CTLs are able to target and destroy cancer cells expressing EBV.
“The receipt of breakthrough therapy designation brings us one step closer to our ultimate goal of making EBV-CTL available to all patients with EBV-LPD, a serious and life-threatening condition with limited treatment options,” said Richard O’Reilly, MD, Chair of the Department of Pediatrics and Chief of the Pediatric Bone Marrow Transplant Service at Memorial Sloan Kettering Cancer Center (MSKCC) in New York, New York.
MSKCC is developing EBV-CTLs in conjunction with Atara Biotherapeutics, Inc.
Breakthrough therapy designation for EBV-CTLs was based on data from 2 clinical trials of EBV-CTLs conducted at MSKCC.
Data from these studies have been submitted for presentation at an upcoming medical conference. Results of a phase 1/2 study of EBV-CTLs were previously presented at the APHON 37th Annual Conference and Exhibit in 2013.
The FDA’s breakthrough therapy designation is designed to expedite the development and review of new drugs for the treatment of serious or life-threatening conditions.
To qualify for this designation, a drug must show credible evidence of a substantial improvement on a clinically significant endpoint over available therapies, or over placebo if there is no available therapy, or in a study that compares the new treatment plus the standard of care to the standard of care alone.
The designation confers several benefits, including intensive FDA guidance and eligibility for submission of a rolling biologic license application.
More AF patients need anticoagulants, guidelines suggest
Results of a large analysis suggest the latest guidelines for atrial fibrillation (AF) recommend anticoagulant therapy for nearly all women with AF and AF patients older than 65.
In 2014, the American Heart Association, American College of Cardiology, and Heart Rhythm Society issued broader guidelines for the use of anticoagulants in AF patients.
A group of researchers wanted to assess how these guidelines would change the use of anticoagulant therapy.
So they evaluated patients enrolled in the ORBIT-AF study, comparing how recommendations from the 2011 AF guidelines and the guidelines issued in 2014 would affect these patients.
Emily O’Brien, PhD, of the Duke Clinical Research Institute in Durham, North Carolina, and her colleagues conducted this research and described their findings in a letter to JAMA Internal Medicine.
The ORBIT-AF study included 10,132 AF patients from 176 sites across the US. Available data included patients’ age, gender, and risk factors such as prior congestive heart failure, high blood pressure, diabetes, and prior stroke.
The researchers found the overall proportion of AF patients recommended for anticoagulants increased from about 72% of patients with the 2011 guidelines to 91% with the newer guidelines.
A similar increase occurred for women with AF. Under the previous guidelines, anticoagulants would have been recommended for about 77% of female AF patients in the study population. Under the new guidelines, 98% of women in the sample population would have enough risk factors to qualify for treatment.
The 2014 guidelines also lower the age at which patients are considered at risk for stroke from 75 to 65.
In the study population, this meant that anticoagulant therapy would be recommended for almost 99% of patients with AF who were older than 65, compared to roughly 80% whose stroke risk was severe enough under the previous criteria.
“The full adoption of the guidelines could reclassify nearly 1 million people with AFib who previously weren’t recommended for treatment with blood thinners,” Dr O’Brien said.
“What we don’t know yet is the extent to which doctors in community practice will incorporate the guidelines into their clinical routines and what that will mean for the long-term outcomes for those patients. That will be the next step for our study.”
Results of a large analysis suggest the latest guidelines for atrial fibrillation (AF) recommend anticoagulant therapy for nearly all women with AF and AF patients older than 65.
In 2014, the American Heart Association, American College of Cardiology, and Heart Rhythm Society issued broader guidelines for the use of anticoagulants in AF patients.
A group of researchers wanted to assess how these guidelines would change the use of anticoagulant therapy.
So they evaluated patients enrolled in the ORBIT-AF study, comparing how recommendations from the 2011 AF guidelines and the guidelines issued in 2014 would affect these patients.
Emily O’Brien, PhD, of the Duke Clinical Research Institute in Durham, North Carolina, and her colleagues conducted this research and described their findings in a letter to JAMA Internal Medicine.
The ORBIT-AF study included 10,132 AF patients from 176 sites across the US. Available data included patients’ age, gender, and risk factors such as prior congestive heart failure, high blood pressure, diabetes, and prior stroke.
The researchers found the overall proportion of AF patients recommended for anticoagulants increased from about 72% of patients with the 2011 guidelines to 91% with the newer guidelines.
A similar increase occurred for women with AF. Under the previous guidelines, anticoagulants would have been recommended for about 77% of female AF patients in the study population. Under the new guidelines, 98% of women in the sample population would have enough risk factors to qualify for treatment.
The 2014 guidelines also lower the age at which patients are considered at risk for stroke from 75 to 65.
In the study population, this meant that anticoagulant therapy would be recommended for almost 99% of patients with AF who were older than 65, compared to roughly 80% whose stroke risk was severe enough under the previous criteria.
“The full adoption of the guidelines could reclassify nearly 1 million people with AFib who previously weren’t recommended for treatment with blood thinners,” Dr O’Brien said.
“What we don’t know yet is the extent to which doctors in community practice will incorporate the guidelines into their clinical routines and what that will mean for the long-term outcomes for those patients. That will be the next step for our study.”
Results of a large analysis suggest the latest guidelines for atrial fibrillation (AF) recommend anticoagulant therapy for nearly all women with AF and AF patients older than 65.
In 2014, the American Heart Association, American College of Cardiology, and Heart Rhythm Society issued broader guidelines for the use of anticoagulants in AF patients.
A group of researchers wanted to assess how these guidelines would change the use of anticoagulant therapy.
So they evaluated patients enrolled in the ORBIT-AF study, comparing how recommendations from the 2011 AF guidelines and the guidelines issued in 2014 would affect these patients.
Emily O’Brien, PhD, of the Duke Clinical Research Institute in Durham, North Carolina, and her colleagues conducted this research and described their findings in a letter to JAMA Internal Medicine.
The ORBIT-AF study included 10,132 AF patients from 176 sites across the US. Available data included patients’ age, gender, and risk factors such as prior congestive heart failure, high blood pressure, diabetes, and prior stroke.
The researchers found the overall proportion of AF patients recommended for anticoagulants increased from about 72% of patients with the 2011 guidelines to 91% with the newer guidelines.
A similar increase occurred for women with AF. Under the previous guidelines, anticoagulants would have been recommended for about 77% of female AF patients in the study population. Under the new guidelines, 98% of women in the sample population would have enough risk factors to qualify for treatment.
The 2014 guidelines also lower the age at which patients are considered at risk for stroke from 75 to 65.
In the study population, this meant that anticoagulant therapy would be recommended for almost 99% of patients with AF who were older than 65, compared to roughly 80% whose stroke risk was severe enough under the previous criteria.
“The full adoption of the guidelines could reclassify nearly 1 million people with AFib who previously weren’t recommended for treatment with blood thinners,” Dr O’Brien said.
“What we don’t know yet is the extent to which doctors in community practice will incorporate the guidelines into their clinical routines and what that will mean for the long-term outcomes for those patients. That will be the next step for our study.”
3D-printed devices can deliver drugs in vitro
ATLANTA—Interventional radiologists say they’ve successfully used 3D printers to develop personalized medical devices that can deliver antibiotics and chemotherapy in a targeted manner in vitro.
Researchers and engineers collaborated to print catheters, stents, and filaments that were bioactive, giving these devices the ability to deliver antibiotics and chemotherapeutic medications to a targeted area in cell cultures.
Horacio R. D’Agostino, MD, of Louisiana State University Health Sciences Center in Shreveport, discussed this work at the 2015 Society of Interventional Radiology’s Annual Scientific Meeting (abstract 13).
“3D printing allows for tailor-made materials for personalized medicine,” Dr D’Agostino said. “It gives us the ability to construct devices that meet patients’ needs, from their unique anatomy to specific medicine requirements. And as tools in interventional radiology, these devices are part of treatment options that are less invasive than traditional surgery.”
Using 3D printing technology and resorbable bioplastics, Dr D’Agostino and his colleagues developed bioactive filaments, chemotherapy beads, and catheters and stents containing antibiotics or chemotherapeutic agents.
The team then tested these devices in cell cultures. They found the antibiotic-containing catheters inhibited E coli growth, and filaments carrying chemotherapeutic agents inhibited the growth of osteosarcoma cells.
“We treat a wide variety of patients and, with some patients, the current one-size-fits-all devices are not an option,” Dr D’Agostino noted. “3D printing gives us the ability to craft devices that are better suited for certain patient populations that are traditionally tough to treat, such as children and the obese, who have different anatomy. There’s limitless potential to be explored with this technology.”
The researchers were also able to print biodegradable filaments, catheters, and stents that contain antibiotics and chemotherapeutic agents. These devices might help patients avoid the need to undergo a second procedure or treatment to remove or destroy the delivery vehicle.
Dr D’Agostino said this early success with 3D-printed instruments in the lab warrants further studies, with the goal of receiving approval to use these devices in humans. He also sees an opportunity to collaborate with other medical specialties to deliver higher-quality, personalized care to all types of patients.
ATLANTA—Interventional radiologists say they’ve successfully used 3D printers to develop personalized medical devices that can deliver antibiotics and chemotherapy in a targeted manner in vitro.
Researchers and engineers collaborated to print catheters, stents, and filaments that were bioactive, giving these devices the ability to deliver antibiotics and chemotherapeutic medications to a targeted area in cell cultures.
Horacio R. D’Agostino, MD, of Louisiana State University Health Sciences Center in Shreveport, discussed this work at the 2015 Society of Interventional Radiology’s Annual Scientific Meeting (abstract 13).
“3D printing allows for tailor-made materials for personalized medicine,” Dr D’Agostino said. “It gives us the ability to construct devices that meet patients’ needs, from their unique anatomy to specific medicine requirements. And as tools in interventional radiology, these devices are part of treatment options that are less invasive than traditional surgery.”
Using 3D printing technology and resorbable bioplastics, Dr D’Agostino and his colleagues developed bioactive filaments, chemotherapy beads, and catheters and stents containing antibiotics or chemotherapeutic agents.
The team then tested these devices in cell cultures. They found the antibiotic-containing catheters inhibited E coli growth, and filaments carrying chemotherapeutic agents inhibited the growth of osteosarcoma cells.
“We treat a wide variety of patients and, with some patients, the current one-size-fits-all devices are not an option,” Dr D’Agostino noted. “3D printing gives us the ability to craft devices that are better suited for certain patient populations that are traditionally tough to treat, such as children and the obese, who have different anatomy. There’s limitless potential to be explored with this technology.”
The researchers were also able to print biodegradable filaments, catheters, and stents that contain antibiotics and chemotherapeutic agents. These devices might help patients avoid the need to undergo a second procedure or treatment to remove or destroy the delivery vehicle.
Dr D’Agostino said this early success with 3D-printed instruments in the lab warrants further studies, with the goal of receiving approval to use these devices in humans. He also sees an opportunity to collaborate with other medical specialties to deliver higher-quality, personalized care to all types of patients.
ATLANTA—Interventional radiologists say they’ve successfully used 3D printers to develop personalized medical devices that can deliver antibiotics and chemotherapy in a targeted manner in vitro.
Researchers and engineers collaborated to print catheters, stents, and filaments that were bioactive, giving these devices the ability to deliver antibiotics and chemotherapeutic medications to a targeted area in cell cultures.
Horacio R. D’Agostino, MD, of Louisiana State University Health Sciences Center in Shreveport, discussed this work at the 2015 Society of Interventional Radiology’s Annual Scientific Meeting (abstract 13).
“3D printing allows for tailor-made materials for personalized medicine,” Dr D’Agostino said. “It gives us the ability to construct devices that meet patients’ needs, from their unique anatomy to specific medicine requirements. And as tools in interventional radiology, these devices are part of treatment options that are less invasive than traditional surgery.”
Using 3D printing technology and resorbable bioplastics, Dr D’Agostino and his colleagues developed bioactive filaments, chemotherapy beads, and catheters and stents containing antibiotics or chemotherapeutic agents.
The team then tested these devices in cell cultures. They found the antibiotic-containing catheters inhibited E coli growth, and filaments carrying chemotherapeutic agents inhibited the growth of osteosarcoma cells.
“We treat a wide variety of patients and, with some patients, the current one-size-fits-all devices are not an option,” Dr D’Agostino noted. “3D printing gives us the ability to craft devices that are better suited for certain patient populations that are traditionally tough to treat, such as children and the obese, who have different anatomy. There’s limitless potential to be explored with this technology.”
The researchers were also able to print biodegradable filaments, catheters, and stents that contain antibiotics and chemotherapeutic agents. These devices might help patients avoid the need to undergo a second procedure or treatment to remove or destroy the delivery vehicle.
Dr D’Agostino said this early success with 3D-printed instruments in the lab warrants further studies, with the goal of receiving approval to use these devices in humans. He also sees an opportunity to collaborate with other medical specialties to deliver higher-quality, personalized care to all types of patients.