User login
Drug may improve outcomes of VOD with MOF after HSCT
Photo by Chad McNeeley
Results of a phase 3 trial suggest defibrotide may improve survival in patients who develop hepatic veno-occlusive disease (VOD) and multi-organ failure (MOF) after hematopoietic stem cell transplant (HSCT).
The patients in this trial had a significant improvement in complete response (CR) rate and survival at day 100 after HSCT, when compared with historical controls.
The researchers said defibrotide was generally well-tolerated, and toxicity was manageable.
However, nearly all defibrotide-treated patients had at least 1 adverse event (AE), as did all historical controls. And a majority of patients in both groups had a fatal AE.
Paul G. Richardson, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues reported these results in Blood. The trial was sponsored by Jazz Pharmaceuticals, makers of defibrotide.
“Based on the results of this pivotal phase 3 study, we believe defibrotide provides a promising treatment option for patients with this urgent unmet need,” Dr Richardson said.
“Although HSCT has improved substantially over the last decade, hepatic [VOD] with MOF remains a very real and life-threatening complication post-HSCT, and for which there are no currently approved therapies."
Dr Richardson and his colleagues investigated the safety and efficacy of defibrotide in 102 adult and pediatric HSCT patients with established hepatic VOD with MOF.
The patients received defibrotide intravenously at 25 mg/kg/day for a minimum of 21 days. Treatment was scheduled to continue beyond 21 days until the resolution of VOD or the patient’s discharge from the hospital.
The researchers compared the 102 patients who received defibrotide with 32 historical controls who were treated at the same institutions. The controls were identified via a review of medical charts of HSCT patients by an independent medical review committee, which was blinded to outcomes.
Baseline characteristics
Baseline characteristics between the groups were largely well balanced. This includes underlying disease, graft source, conditioning regimen, myeloablative regimen, and VOD and MOF parameters.
However, 15% of defibrotide-treated patients received tacrolimus plus sirolimus as graft-versus-host disease prophylaxis, compared with none of the historical controls. Most patients discontinued this regimen upon diagnosis of VOD.
All patients had hyperbilirubinemia. Ascites, weight gain, and hepatomegaly were present in 72% of patients in the defibrotide group and 59% of historical controls.
Renal dysfunction was present in 78% of patients in the defibrotide group (20% dialysis-dependent) and 75% of historical controls (6% dialysis-dependent). Pulmonary dysfunction was present in 85% (26% ventilator-dependent) and 97% (19% ventilator-dependent), respectively.
Sixty-four percent of patients in the defibrotide group and 72% of historical controls had both renal and pulmonary dysfunction.
Response and survival
The primary endpoint was survival at day 100 post-HSCT, which was 38.2% in the defibrotide group and 25% in the historical control group. The estimated between-group difference, using a propensity-adjusted analysis, was 23% (P=0.0109).
The CR rate was 25.5% in the defibrotide group and 12.5% in the historical control group. The estimated difference, adjusted for propensity score, was 19% (P=0.0160).
The median time to CR was 34.5 days in the defibrotide group and 39.5 days in the control group. CR was durable for 22 of 26 patients in the defibrotide group, who still had a CR at last observation. Four patients in the defibrotide group had CR end dates before day 180. All 4 patients died of sepsis or leukemia.
In the historical control group, 1 patient had a durable CR (162 days), 2 patients had a limited CR duration (9 and 10 days, respectively), and 1 patient could not be assessed.
Safety
The median duration of defibrotide treatment was 21.5 days. Eleven patients discontinued treatment prematurely due to possible drug-related toxicity (10.7%).
All but 1 of the defibrotide-treated patients and all historical controls had at least 1 AE. Hypotension was the most common AE in both groups—39.2% with defibrotide and 50.0% for historical controls. Diarrhea was also common—23.5% and 37.5%, respectively.
Sixty-four percent of patients in the defibrotide group (n=65) and 69% of historical controls (n=22) had a fatal AE.
Fifteen patients (14.7%) in the defibrotide group and 2 (6.3%) in the historical control group had 1 or more hemorrhagic AEs leading to death.
For the defibrotide group, these were gastrointestinal hemorrhage (n=1), cerebral hemorrhage (n=2), intracranial hemorrhage (n=1), subarachnoid hemorrhage (n=1), pulmonary alveolar hemorrhage (n=7), pulmonary hemorrhage (n=2), and vascular disorders hemorrhage (n=1).
Both hemorrhagic AEs leading to death in historical controls were pulmonary alveolar hemorrhage. 
Photo by Chad McNeeley
Results of a phase 3 trial suggest defibrotide may improve survival in patients who develop hepatic veno-occlusive disease (VOD) and multi-organ failure (MOF) after hematopoietic stem cell transplant (HSCT).
The patients in this trial had a significant improvement in complete response (CR) rate and survival at day 100 after HSCT, when compared with historical controls.
The researchers said defibrotide was generally well-tolerated, and toxicity was manageable.
However, nearly all defibrotide-treated patients had at least 1 adverse event (AE), as did all historical controls. And a majority of patients in both groups had a fatal AE.
Paul G. Richardson, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues reported these results in Blood. The trial was sponsored by Jazz Pharmaceuticals, makers of defibrotide.
“Based on the results of this pivotal phase 3 study, we believe defibrotide provides a promising treatment option for patients with this urgent unmet need,” Dr Richardson said.
“Although HSCT has improved substantially over the last decade, hepatic [VOD] with MOF remains a very real and life-threatening complication post-HSCT, and for which there are no currently approved therapies."
Dr Richardson and his colleagues investigated the safety and efficacy of defibrotide in 102 adult and pediatric HSCT patients with established hepatic VOD with MOF.
The patients received defibrotide intravenously at 25 mg/kg/day for a minimum of 21 days. Treatment was scheduled to continue beyond 21 days until the resolution of VOD or the patient’s discharge from the hospital.
The researchers compared the 102 patients who received defibrotide with 32 historical controls who were treated at the same institutions. The controls were identified via a review of medical charts of HSCT patients by an independent medical review committee, which was blinded to outcomes.
Baseline characteristics
Baseline characteristics between the groups were largely well balanced. This includes underlying disease, graft source, conditioning regimen, myeloablative regimen, and VOD and MOF parameters.
However, 15% of defibrotide-treated patients received tacrolimus plus sirolimus as graft-versus-host disease prophylaxis, compared with none of the historical controls. Most patients discontinued this regimen upon diagnosis of VOD.
All patients had hyperbilirubinemia. Ascites, weight gain, and hepatomegaly were present in 72% of patients in the defibrotide group and 59% of historical controls.
Renal dysfunction was present in 78% of patients in the defibrotide group (20% dialysis-dependent) and 75% of historical controls (6% dialysis-dependent). Pulmonary dysfunction was present in 85% (26% ventilator-dependent) and 97% (19% ventilator-dependent), respectively.
Sixty-four percent of patients in the defibrotide group and 72% of historical controls had both renal and pulmonary dysfunction.
Response and survival
The primary endpoint was survival at day 100 post-HSCT, which was 38.2% in the defibrotide group and 25% in the historical control group. The estimated between-group difference, using a propensity-adjusted analysis, was 23% (P=0.0109).
The CR rate was 25.5% in the defibrotide group and 12.5% in the historical control group. The estimated difference, adjusted for propensity score, was 19% (P=0.0160).
The median time to CR was 34.5 days in the defibrotide group and 39.5 days in the control group. CR was durable for 22 of 26 patients in the defibrotide group, who still had a CR at last observation. Four patients in the defibrotide group had CR end dates before day 180. All 4 patients died of sepsis or leukemia.
In the historical control group, 1 patient had a durable CR (162 days), 2 patients had a limited CR duration (9 and 10 days, respectively), and 1 patient could not be assessed.
Safety
The median duration of defibrotide treatment was 21.5 days. Eleven patients discontinued treatment prematurely due to possible drug-related toxicity (10.7%).
All but 1 of the defibrotide-treated patients and all historical controls had at least 1 AE. Hypotension was the most common AE in both groups—39.2% with defibrotide and 50.0% for historical controls. Diarrhea was also common—23.5% and 37.5%, respectively.
Sixty-four percent of patients in the defibrotide group (n=65) and 69% of historical controls (n=22) had a fatal AE.
Fifteen patients (14.7%) in the defibrotide group and 2 (6.3%) in the historical control group had 1 or more hemorrhagic AEs leading to death.
For the defibrotide group, these were gastrointestinal hemorrhage (n=1), cerebral hemorrhage (n=2), intracranial hemorrhage (n=1), subarachnoid hemorrhage (n=1), pulmonary alveolar hemorrhage (n=7), pulmonary hemorrhage (n=2), and vascular disorders hemorrhage (n=1).
Both hemorrhagic AEs leading to death in historical controls were pulmonary alveolar hemorrhage.
Photo by Chad McNeeley
Results of a phase 3 trial suggest defibrotide may improve survival in patients who develop hepatic veno-occlusive disease (VOD) and multi-organ failure (MOF) after hematopoietic stem cell transplant (HSCT).
The patients in this trial had a significant improvement in complete response (CR) rate and survival at day 100 after HSCT, when compared with historical controls.
The researchers said defibrotide was generally well-tolerated, and toxicity was manageable.
However, nearly all defibrotide-treated patients had at least 1 adverse event (AE), as did all historical controls. And a majority of patients in both groups had a fatal AE.
Paul G. Richardson, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues reported these results in Blood. The trial was sponsored by Jazz Pharmaceuticals, makers of defibrotide.
“Based on the results of this pivotal phase 3 study, we believe defibrotide provides a promising treatment option for patients with this urgent unmet need,” Dr Richardson said.
“Although HSCT has improved substantially over the last decade, hepatic [VOD] with MOF remains a very real and life-threatening complication post-HSCT, and for which there are no currently approved therapies."
Dr Richardson and his colleagues investigated the safety and efficacy of defibrotide in 102 adult and pediatric HSCT patients with established hepatic VOD with MOF.
The patients received defibrotide intravenously at 25 mg/kg/day for a minimum of 21 days. Treatment was scheduled to continue beyond 21 days until the resolution of VOD or the patient’s discharge from the hospital.
The researchers compared the 102 patients who received defibrotide with 32 historical controls who were treated at the same institutions. The controls were identified via a review of medical charts of HSCT patients by an independent medical review committee, which was blinded to outcomes.
Baseline characteristics
Baseline characteristics between the groups were largely well balanced. This includes underlying disease, graft source, conditioning regimen, myeloablative regimen, and VOD and MOF parameters.
However, 15% of defibrotide-treated patients received tacrolimus plus sirolimus as graft-versus-host disease prophylaxis, compared with none of the historical controls. Most patients discontinued this regimen upon diagnosis of VOD.
All patients had hyperbilirubinemia. Ascites, weight gain, and hepatomegaly were present in 72% of patients in the defibrotide group and 59% of historical controls.
Renal dysfunction was present in 78% of patients in the defibrotide group (20% dialysis-dependent) and 75% of historical controls (6% dialysis-dependent). Pulmonary dysfunction was present in 85% (26% ventilator-dependent) and 97% (19% ventilator-dependent), respectively.
Sixty-four percent of patients in the defibrotide group and 72% of historical controls had both renal and pulmonary dysfunction.
Response and survival
The primary endpoint was survival at day 100 post-HSCT, which was 38.2% in the defibrotide group and 25% in the historical control group. The estimated between-group difference, using a propensity-adjusted analysis, was 23% (P=0.0109).
The CR rate was 25.5% in the defibrotide group and 12.5% in the historical control group. The estimated difference, adjusted for propensity score, was 19% (P=0.0160).
The median time to CR was 34.5 days in the defibrotide group and 39.5 days in the control group. CR was durable for 22 of 26 patients in the defibrotide group, who still had a CR at last observation. Four patients in the defibrotide group had CR end dates before day 180. All 4 patients died of sepsis or leukemia.
In the historical control group, 1 patient had a durable CR (162 days), 2 patients had a limited CR duration (9 and 10 days, respectively), and 1 patient could not be assessed.
Safety
The median duration of defibrotide treatment was 21.5 days. Eleven patients discontinued treatment prematurely due to possible drug-related toxicity (10.7%).
All but 1 of the defibrotide-treated patients and all historical controls had at least 1 AE. Hypotension was the most common AE in both groups—39.2% with defibrotide and 50.0% for historical controls. Diarrhea was also common—23.5% and 37.5%, respectively.
Sixty-four percent of patients in the defibrotide group (n=65) and 69% of historical controls (n=22) had a fatal AE.
Fifteen patients (14.7%) in the defibrotide group and 2 (6.3%) in the historical control group had 1 or more hemorrhagic AEs leading to death.
For the defibrotide group, these were gastrointestinal hemorrhage (n=1), cerebral hemorrhage (n=2), intracranial hemorrhage (n=1), subarachnoid hemorrhage (n=1), pulmonary alveolar hemorrhage (n=7), pulmonary hemorrhage (n=2), and vascular disorders hemorrhage (n=1).
Both hemorrhagic AEs leading to death in historical controls were pulmonary alveolar hemorrhage.
Journal questions results of rivaroxaban trial
An investigation by The BMJ has called into question the validity of the ROCKET AF trial, which was used to support approval for the direct oral anticoagulant rivaroxaban (Xarelto) in the US and European Union (EU).
For this trial, which was published in NEJM in 2011, researchers compared rivaroxaban to warfarin in patients with nonvalvular atrial fibrillation.
Results suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism.
And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.
However, The BMJ article questions these results because the Alere INRatio Monitor System (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips), which was used to measure patients’ international
normalized ratios (INRs) during the trial, was recalled in December 2014 after giving falsely low test results.
“In terms of the trial results, [the defect with the system] could make rivaroxaban seem safer than it was with respect to the risk of bleeding and throws doubt onto outcomes used to support the use of the world’s best-selling new oral anticoagulant,” said Deborah Cohen, The BMJ’s associate editor and author of the article.
In November 2015, the European Medicines Agency told The BMJ they were investigating the potential implications of the issue with the INRatio system. And the US Food and Drug Administration (FDA) said they were “aware of concerns regarding the INRatio device and its use in the ROCKET AF trial and [were] reviewing relevant data.”
The makers of the INRatio system (Alere) confirmed that the fault dates back to 2002. However, neither they nor the FDA responded to questions about why nothing had been done about the problem earlier.
In the meantime, Harlan Krumholz, MD, of Yale University in New Haven, Connecticut, said NEJM should place an “immediate Expression of Concern” on the paper describing ROCKET AF to notify the medical community, and there should be “an investigation by an independent group of experts to quickly determine if there are grounds for retraction.”
In December, Duke University’s Clinical Research Institute, which carried out the trial on behalf of Johnson and Johnson and Bayer Healthcare, said analyses conducted after the ROCKET AF trial was first published “are consistent with the results from the original trial and do not alter the conclusions of ROCKET AF.”
But former FDA reviewer Thomas Marciniak, MD, told The BMJ he would not rely on any re-analyses done by Duke, Johnson and Johnson, or the FDA. He added that public release of the data is “the only solution that would lead to unbiased analyses.”
However, Bayer told The BMJ the company has only signed up to share information on “study reports for new medicines approved in the US and the EU after January 1, 2014.”
According to former FDA clinical pharmacologist Bob Powell, PharmD, once a drug is on the market, the regulators lack a mandate to act without a safety signal.
“It is this lack of safety signal that appears to be hindering the FDA in their desire to pursue tailored dosing for [direct oral anticoagulants],” he said. “If it turns out that the issue with the INRatio device changes the safety profile of rivaroxaban, this very well may constitute the safety signal necessary for the FDA to act in this regard.”
An investigation by The BMJ has called into question the validity of the ROCKET AF trial, which was used to support approval for the direct oral anticoagulant rivaroxaban (Xarelto) in the US and European Union (EU).
For this trial, which was published in NEJM in 2011, researchers compared rivaroxaban to warfarin in patients with nonvalvular atrial fibrillation.
Results suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism.
And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.
However, The BMJ article questions these results because the Alere INRatio Monitor System (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips), which was used to measure patients’ international
normalized ratios (INRs) during the trial, was recalled in December 2014 after giving falsely low test results.
“In terms of the trial results, [the defect with the system] could make rivaroxaban seem safer than it was with respect to the risk of bleeding and throws doubt onto outcomes used to support the use of the world’s best-selling new oral anticoagulant,” said Deborah Cohen, The BMJ’s associate editor and author of the article.
In November 2015, the European Medicines Agency told The BMJ they were investigating the potential implications of the issue with the INRatio system. And the US Food and Drug Administration (FDA) said they were “aware of concerns regarding the INRatio device and its use in the ROCKET AF trial and [were] reviewing relevant data.”
The makers of the INRatio system (Alere) confirmed that the fault dates back to 2002. However, neither they nor the FDA responded to questions about why nothing had been done about the problem earlier.
In the meantime, Harlan Krumholz, MD, of Yale University in New Haven, Connecticut, said NEJM should place an “immediate Expression of Concern” on the paper describing ROCKET AF to notify the medical community, and there should be “an investigation by an independent group of experts to quickly determine if there are grounds for retraction.”
In December, Duke University’s Clinical Research Institute, which carried out the trial on behalf of Johnson and Johnson and Bayer Healthcare, said analyses conducted after the ROCKET AF trial was first published “are consistent with the results from the original trial and do not alter the conclusions of ROCKET AF.”
But former FDA reviewer Thomas Marciniak, MD, told The BMJ he would not rely on any re-analyses done by Duke, Johnson and Johnson, or the FDA. He added that public release of the data is “the only solution that would lead to unbiased analyses.”
However, Bayer told The BMJ the company has only signed up to share information on “study reports for new medicines approved in the US and the EU after January 1, 2014.”
According to former FDA clinical pharmacologist Bob Powell, PharmD, once a drug is on the market, the regulators lack a mandate to act without a safety signal.
“It is this lack of safety signal that appears to be hindering the FDA in their desire to pursue tailored dosing for [direct oral anticoagulants],” he said. “If it turns out that the issue with the INRatio device changes the safety profile of rivaroxaban, this very well may constitute the safety signal necessary for the FDA to act in this regard.”
An investigation by The BMJ has called into question the validity of the ROCKET AF trial, which was used to support approval for the direct oral anticoagulant rivaroxaban (Xarelto) in the US and European Union (EU).
For this trial, which was published in NEJM in 2011, researchers compared rivaroxaban to warfarin in patients with nonvalvular atrial fibrillation.
Results suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism.
And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.
However, The BMJ article questions these results because the Alere INRatio Monitor System (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips), which was used to measure patients’ international
normalized ratios (INRs) during the trial, was recalled in December 2014 after giving falsely low test results.
“In terms of the trial results, [the defect with the system] could make rivaroxaban seem safer than it was with respect to the risk of bleeding and throws doubt onto outcomes used to support the use of the world’s best-selling new oral anticoagulant,” said Deborah Cohen, The BMJ’s associate editor and author of the article.
In November 2015, the European Medicines Agency told The BMJ they were investigating the potential implications of the issue with the INRatio system. And the US Food and Drug Administration (FDA) said they were “aware of concerns regarding the INRatio device and its use in the ROCKET AF trial and [were] reviewing relevant data.”
The makers of the INRatio system (Alere) confirmed that the fault dates back to 2002. However, neither they nor the FDA responded to questions about why nothing had been done about the problem earlier.
In the meantime, Harlan Krumholz, MD, of Yale University in New Haven, Connecticut, said NEJM should place an “immediate Expression of Concern” on the paper describing ROCKET AF to notify the medical community, and there should be “an investigation by an independent group of experts to quickly determine if there are grounds for retraction.”
In December, Duke University’s Clinical Research Institute, which carried out the trial on behalf of Johnson and Johnson and Bayer Healthcare, said analyses conducted after the ROCKET AF trial was first published “are consistent with the results from the original trial and do not alter the conclusions of ROCKET AF.”
But former FDA reviewer Thomas Marciniak, MD, told The BMJ he would not rely on any re-analyses done by Duke, Johnson and Johnson, or the FDA. He added that public release of the data is “the only solution that would lead to unbiased analyses.”
However, Bayer told The BMJ the company has only signed up to share information on “study reports for new medicines approved in the US and the EU after January 1, 2014.”
According to former FDA clinical pharmacologist Bob Powell, PharmD, once a drug is on the market, the regulators lack a mandate to act without a safety signal.
“It is this lack of safety signal that appears to be hindering the FDA in their desire to pursue tailored dosing for [direct oral anticoagulants],” he said. “If it turns out that the issue with the INRatio device changes the safety profile of rivaroxaban, this very well may constitute the safety signal necessary for the FDA to act in this regard.”
EHA creates ‘roadmap’ for hematology research
Photo by Daniel Sone
The European Hematology Association (EHA) has created a “roadmap” for hematology research in Europe.
This guidance document summarizes the current status of basic, translational, and clinical hematology research and identifies areas of unmet scientific and medical need in Europe.
It is intended to help European and national policy makers, funding agencies, charities, research institutes, and researchers make decisions on initiating, funding, or developing research.
The guidance, “The European Hematology Association Roadmap for European Hematology Research: A Consensus Document,” is published in this month’s issue of haematologica.
“For the first time, hematologists in Europe came together to develop a roadmap to guide hematology research in Europe” said Andreas Engert, MD, chair of the EHA Research Roadmap Task Force.
“Hematology in Europe has achieved a lot, but the discipline must focus and collaborate to be efficient and remain successful in improving patient outcomes. The roadmap does just that and will determine the research agenda in Europe in the coming years.”
Roughly 300 experts from more than 20 countries—including clinicians, basic researchers, and patients—contributed to the roadmap. Stakeholders such as national hematology societies, patient organizations, hematology trial groups, and other European organizations were consulted to comment on the final draft version.
The final roadmap has 9 sections: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation.
The roadmap lists priorities and needs in these areas, including the need for targeted therapies based on genomic profiling and chemical biology, the need to eradicate minimal residual disease, and the need for treatments that are better tolerated by elderly patients.
“Now’s the time for Europe to pay attention,” said Ulrich Jäger, MD, chair of the EHA European Affairs Committee.
“With an aging population, the slow recovery from the financial and Euro crises, costly medical breakthroughs and innovations—quite a few of which involve hematology researchers—Europe faces increased health expenditures while budgets are limited.”
“Policy makers are rightfully cautious when spending the taxpayers’ money. So it is our responsibility to provide the policy makers with the information and evidence they need to decide where their support impacts knowledge and health most efficiently, to the benefit of patients and society. The Research Roadmap delivers on that. Now, it is up to the policy makers in the EU to deliver too.”
Photo by Daniel Sone
The European Hematology Association (EHA) has created a “roadmap” for hematology research in Europe.
This guidance document summarizes the current status of basic, translational, and clinical hematology research and identifies areas of unmet scientific and medical need in Europe.
It is intended to help European and national policy makers, funding agencies, charities, research institutes, and researchers make decisions on initiating, funding, or developing research.
The guidance, “The European Hematology Association Roadmap for European Hematology Research: A Consensus Document,” is published in this month’s issue of haematologica.
“For the first time, hematologists in Europe came together to develop a roadmap to guide hematology research in Europe” said Andreas Engert, MD, chair of the EHA Research Roadmap Task Force.
“Hematology in Europe has achieved a lot, but the discipline must focus and collaborate to be efficient and remain successful in improving patient outcomes. The roadmap does just that and will determine the research agenda in Europe in the coming years.”
Roughly 300 experts from more than 20 countries—including clinicians, basic researchers, and patients—contributed to the roadmap. Stakeholders such as national hematology societies, patient organizations, hematology trial groups, and other European organizations were consulted to comment on the final draft version.
The final roadmap has 9 sections: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation.
The roadmap lists priorities and needs in these areas, including the need for targeted therapies based on genomic profiling and chemical biology, the need to eradicate minimal residual disease, and the need for treatments that are better tolerated by elderly patients.
“Now’s the time for Europe to pay attention,” said Ulrich Jäger, MD, chair of the EHA European Affairs Committee.
“With an aging population, the slow recovery from the financial and Euro crises, costly medical breakthroughs and innovations—quite a few of which involve hematology researchers—Europe faces increased health expenditures while budgets are limited.”
“Policy makers are rightfully cautious when spending the taxpayers’ money. So it is our responsibility to provide the policy makers with the information and evidence they need to decide where their support impacts knowledge and health most efficiently, to the benefit of patients and society. The Research Roadmap delivers on that. Now, it is up to the policy makers in the EU to deliver too.”
Photo by Daniel Sone
The European Hematology Association (EHA) has created a “roadmap” for hematology research in Europe.
This guidance document summarizes the current status of basic, translational, and clinical hematology research and identifies areas of unmet scientific and medical need in Europe.
It is intended to help European and national policy makers, funding agencies, charities, research institutes, and researchers make decisions on initiating, funding, or developing research.
The guidance, “The European Hematology Association Roadmap for European Hematology Research: A Consensus Document,” is published in this month’s issue of haematologica.
“For the first time, hematologists in Europe came together to develop a roadmap to guide hematology research in Europe” said Andreas Engert, MD, chair of the EHA Research Roadmap Task Force.
“Hematology in Europe has achieved a lot, but the discipline must focus and collaborate to be efficient and remain successful in improving patient outcomes. The roadmap does just that and will determine the research agenda in Europe in the coming years.”
Roughly 300 experts from more than 20 countries—including clinicians, basic researchers, and patients—contributed to the roadmap. Stakeholders such as national hematology societies, patient organizations, hematology trial groups, and other European organizations were consulted to comment on the final draft version.
The final roadmap has 9 sections: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation.
The roadmap lists priorities and needs in these areas, including the need for targeted therapies based on genomic profiling and chemical biology, the need to eradicate minimal residual disease, and the need for treatments that are better tolerated by elderly patients.
“Now’s the time for Europe to pay attention,” said Ulrich Jäger, MD, chair of the EHA European Affairs Committee.
“With an aging population, the slow recovery from the financial and Euro crises, costly medical breakthroughs and innovations—quite a few of which involve hematology researchers—Europe faces increased health expenditures while budgets are limited.”
“Policy makers are rightfully cautious when spending the taxpayers’ money. So it is our responsibility to provide the policy makers with the information and evidence they need to decide where their support impacts knowledge and health most efficiently, to the benefit of patients and society. The Research Roadmap delivers on that. Now, it is up to the policy makers in the EU to deliver too.”
Olfactory receptor could be target for AML therapy
Investigators have discovered that an olfactory receptor in white blood cells responds to Sandalore, a synthetic odorant with a sandalwood note.
The team identified 7 olfactory receptors in a chronic myeloid leukemia (CML) cell line that were also present in white blood cells from patients with acute myeloid leukemia (AML).
One of the highest expressed receptors, OR2AT4, responded to Sandalore by fighting off the leukemia.
The investigators believe this finding could aid the development of new treatment for AML.
Hanns Hatt, PhD, DrMed, of the Ruhr-Universität Bochum in Germany, and his colleagues described this work in Cell Death Discovery.
The team found 7 olfactory receptors in the CML cell line K562—OR51B4, OR51B5, OR52D1, OR2W3, OR2B6, OR2AT4, and OR51I2. These receptors were also expressed in samples from AML patients.
The investigators then found that OR2AT4, one of the highest expressed olfactory receptors, is activated by Sandalore.
If Sandalore was used to activate the receptor, it inhibited leukemia cell proliferation and induced apoptosis in the leukemia cells. It also induced erythroid differentiation.
In 2014, Dr Hatt and his colleagues discovered that OR2AT4 is present in skin cells and that, by activating it with sandalwood aroma, wound healing is promoted. Through a series of tests, the team identified the signaling pathways underlying the observed effects.
With the current study, the investigators found that if Sandalore activates OR2AT4 in the context of CML or AML, processes similar to those in the olfactory cells in the nose start in blood cells.
The concentration of calcium ions in the cells increases. This, in turn, activates signaling pathways in which phosphate groups are transmitted to MAP kinases.
“This could be a new starting point for the development of leukemia treatment,” Dr Hatt said. “Acute myeloid leukemia, in particular, is a disease for which specific medication is not, as yet, available.”
Investigators have discovered that an olfactory receptor in white blood cells responds to Sandalore, a synthetic odorant with a sandalwood note.
The team identified 7 olfactory receptors in a chronic myeloid leukemia (CML) cell line that were also present in white blood cells from patients with acute myeloid leukemia (AML).
One of the highest expressed receptors, OR2AT4, responded to Sandalore by fighting off the leukemia.
The investigators believe this finding could aid the development of new treatment for AML.
Hanns Hatt, PhD, DrMed, of the Ruhr-Universität Bochum in Germany, and his colleagues described this work in Cell Death Discovery.
The team found 7 olfactory receptors in the CML cell line K562—OR51B4, OR51B5, OR52D1, OR2W3, OR2B6, OR2AT4, and OR51I2. These receptors were also expressed in samples from AML patients.
The investigators then found that OR2AT4, one of the highest expressed olfactory receptors, is activated by Sandalore.
If Sandalore was used to activate the receptor, it inhibited leukemia cell proliferation and induced apoptosis in the leukemia cells. It also induced erythroid differentiation.
In 2014, Dr Hatt and his colleagues discovered that OR2AT4 is present in skin cells and that, by activating it with sandalwood aroma, wound healing is promoted. Through a series of tests, the team identified the signaling pathways underlying the observed effects.
With the current study, the investigators found that if Sandalore activates OR2AT4 in the context of CML or AML, processes similar to those in the olfactory cells in the nose start in blood cells.
The concentration of calcium ions in the cells increases. This, in turn, activates signaling pathways in which phosphate groups are transmitted to MAP kinases.
“This could be a new starting point for the development of leukemia treatment,” Dr Hatt said. “Acute myeloid leukemia, in particular, is a disease for which specific medication is not, as yet, available.”
Investigators have discovered that an olfactory receptor in white blood cells responds to Sandalore, a synthetic odorant with a sandalwood note.
The team identified 7 olfactory receptors in a chronic myeloid leukemia (CML) cell line that were also present in white blood cells from patients with acute myeloid leukemia (AML).
One of the highest expressed receptors, OR2AT4, responded to Sandalore by fighting off the leukemia.
The investigators believe this finding could aid the development of new treatment for AML.
Hanns Hatt, PhD, DrMed, of the Ruhr-Universität Bochum in Germany, and his colleagues described this work in Cell Death Discovery.
The team found 7 olfactory receptors in the CML cell line K562—OR51B4, OR51B5, OR52D1, OR2W3, OR2B6, OR2AT4, and OR51I2. These receptors were also expressed in samples from AML patients.
The investigators then found that OR2AT4, one of the highest expressed olfactory receptors, is activated by Sandalore.
If Sandalore was used to activate the receptor, it inhibited leukemia cell proliferation and induced apoptosis in the leukemia cells. It also induced erythroid differentiation.
In 2014, Dr Hatt and his colleagues discovered that OR2AT4 is present in skin cells and that, by activating it with sandalwood aroma, wound healing is promoted. Through a series of tests, the team identified the signaling pathways underlying the observed effects.
With the current study, the investigators found that if Sandalore activates OR2AT4 in the context of CML or AML, processes similar to those in the olfactory cells in the nose start in blood cells.
The concentration of calcium ions in the cells increases. This, in turn, activates signaling pathways in which phosphate groups are transmitted to MAP kinases.
“This could be a new starting point for the development of leukemia treatment,” Dr Hatt said. “Acute myeloid leukemia, in particular, is a disease for which specific medication is not, as yet, available.”
Reducing the risk of Zika transmission via transfusion
The continued spread of the Zika virus has raised concerns about transmission via blood transfusion.
So organizations in the US are asking people who have visited Zika outbreak zones to defer their plans to donate blood.
The US Food and Drug Administration is currently reviewing its blood donation policy with regard to the virus, but the American Red Cross and AABB are recommending donor self-deferral.
Both organizations said people should refrain from donating blood for 28 days if they have visited Mexico, the Caribbean, Central America, or South America in the past 4 weeks.
AABB said blood collection facilities should implement self-deferral, but blood-center-documented donor deferral is not required.
AABB has also recommended that donors who don’t defer call the blood collection facility if they travelled to Zika outbreak areas or other tropical areas and develop an unexplained illness that includes 2 or more symptoms common to Zika, dengue, and chikungunya virus infection in the 14 days after they donate blood.
In addition, blood collection facilities should recall nontransfused products if an infected donor reports experiencing 2 or more such symptoms.
And if a blood collection facility receives a post-donation report of a confirmed case of Zika, the facility should recall any in-date products collected in the 14 days before the onset of symptoms and defer the donor for 28 days after the symptoms are resolved.
About the virus
Zika is a flavivirus transmitted by Aedes mosquitoes. The virus was first described in Africa, but it began to cause epidemics in the Pacific in 2007. In 2015, Zika was found in Brazil, and local transmission has since been reported in more than 20 countries and territories in the Western Hemisphere.
When symptomatic, Zika infection typically causes a mild illness characterized by fever, myalgia, rash, retro-orbital pain, and prostration. However, asymptomatic infection occurs in about 80% of Zika-infected individuals.
Microcephaly has been linked to the ongoing Zika epidemic in Brazil, although the connection has not been confirmed. It has been suggested that microcephaly may be a result of maternal transmission of the Zika virus to the fetus.
During the French Polynesian outbreak of Zika virus that occurred in 2013, there was a 20-fold increase in the number of individuals diagnosed with Guillain-Barré syndrome.
It is not clear what risk the Zika virus poses to the blood supply, but the potential for transfusion transmission was suggested during the French Polynesian outbreak.
The maximum duration of viremia is thought to be less than 28 days, which is why AABB and American Red Cross are recommending a 28-day deferral period for blood donors who may have the virus.
The continued spread of the Zika virus has raised concerns about transmission via blood transfusion.
So organizations in the US are asking people who have visited Zika outbreak zones to defer their plans to donate blood.
The US Food and Drug Administration is currently reviewing its blood donation policy with regard to the virus, but the American Red Cross and AABB are recommending donor self-deferral.
Both organizations said people should refrain from donating blood for 28 days if they have visited Mexico, the Caribbean, Central America, or South America in the past 4 weeks.
AABB said blood collection facilities should implement self-deferral, but blood-center-documented donor deferral is not required.
AABB has also recommended that donors who don’t defer call the blood collection facility if they travelled to Zika outbreak areas or other tropical areas and develop an unexplained illness that includes 2 or more symptoms common to Zika, dengue, and chikungunya virus infection in the 14 days after they donate blood.
In addition, blood collection facilities should recall nontransfused products if an infected donor reports experiencing 2 or more such symptoms.
And if a blood collection facility receives a post-donation report of a confirmed case of Zika, the facility should recall any in-date products collected in the 14 days before the onset of symptoms and defer the donor for 28 days after the symptoms are resolved.
About the virus
Zika is a flavivirus transmitted by Aedes mosquitoes. The virus was first described in Africa, but it began to cause epidemics in the Pacific in 2007. In 2015, Zika was found in Brazil, and local transmission has since been reported in more than 20 countries and territories in the Western Hemisphere.
When symptomatic, Zika infection typically causes a mild illness characterized by fever, myalgia, rash, retro-orbital pain, and prostration. However, asymptomatic infection occurs in about 80% of Zika-infected individuals.
Microcephaly has been linked to the ongoing Zika epidemic in Brazil, although the connection has not been confirmed. It has been suggested that microcephaly may be a result of maternal transmission of the Zika virus to the fetus.
During the French Polynesian outbreak of Zika virus that occurred in 2013, there was a 20-fold increase in the number of individuals diagnosed with Guillain-Barré syndrome.
It is not clear what risk the Zika virus poses to the blood supply, but the potential for transfusion transmission was suggested during the French Polynesian outbreak.
The maximum duration of viremia is thought to be less than 28 days, which is why AABB and American Red Cross are recommending a 28-day deferral period for blood donors who may have the virus.
The continued spread of the Zika virus has raised concerns about transmission via blood transfusion.
So organizations in the US are asking people who have visited Zika outbreak zones to defer their plans to donate blood.
The US Food and Drug Administration is currently reviewing its blood donation policy with regard to the virus, but the American Red Cross and AABB are recommending donor self-deferral.
Both organizations said people should refrain from donating blood for 28 days if they have visited Mexico, the Caribbean, Central America, or South America in the past 4 weeks.
AABB said blood collection facilities should implement self-deferral, but blood-center-documented donor deferral is not required.
AABB has also recommended that donors who don’t defer call the blood collection facility if they travelled to Zika outbreak areas or other tropical areas and develop an unexplained illness that includes 2 or more symptoms common to Zika, dengue, and chikungunya virus infection in the 14 days after they donate blood.
In addition, blood collection facilities should recall nontransfused products if an infected donor reports experiencing 2 or more such symptoms.
And if a blood collection facility receives a post-donation report of a confirmed case of Zika, the facility should recall any in-date products collected in the 14 days before the onset of symptoms and defer the donor for 28 days after the symptoms are resolved.
About the virus
Zika is a flavivirus transmitted by Aedes mosquitoes. The virus was first described in Africa, but it began to cause epidemics in the Pacific in 2007. In 2015, Zika was found in Brazil, and local transmission has since been reported in more than 20 countries and territories in the Western Hemisphere.
When symptomatic, Zika infection typically causes a mild illness characterized by fever, myalgia, rash, retro-orbital pain, and prostration. However, asymptomatic infection occurs in about 80% of Zika-infected individuals.
Microcephaly has been linked to the ongoing Zika epidemic in Brazil, although the connection has not been confirmed. It has been suggested that microcephaly may be a result of maternal transmission of the Zika virus to the fetus.
During the French Polynesian outbreak of Zika virus that occurred in 2013, there was a 20-fold increase in the number of individuals diagnosed with Guillain-Barré syndrome.
It is not clear what risk the Zika virus poses to the blood supply, but the potential for transfusion transmission was suggested during the French Polynesian outbreak.
The maximum duration of viremia is thought to be less than 28 days, which is why AABB and American Red Cross are recommending a 28-day deferral period for blood donors who may have the virus.
When loved ones get cancer, people turn to the Web
chemotherapy
Photo by Rhoda Baer
Loved ones of cancer patients often turn to the Internet for further information about the disease, but they are less inclined to seek emotional support from social media forums, according to a study published in Computers, Informatics, Nursing.
It is fairly common for loved ones of cancer patients to develop depression or anxiety disorders as a result of the diagnosis, but there aren’t many studies focusing specifically on cancer patients’ caregivers and family members, said study author Carolyn Lauckner, PhD, of the University of Georgia in Athens.
“I think, sometimes, the loved ones and caregivers get forgotten about,” she said. “And that’s why I wanted to research this population to see if there are ways that we can better support these individuals.”
Dr Lauckner surveyed 191 people whose loved ones were diagnosed with cancer in the past year or who were currently acting as caregivers to someone with cancer. The motivation behind the research was personal for Dr Lauckner.
“I went through a period of time where I had 3 loved ones diagnosed within a short amount of time,” she said. “I had these experiences where I heard about the diagnosis and I would go online to look it up, and then I would immediately become terrified and freak out about all the stuff I read online.”
Like Dr Lauckner, more than 75% of the subjects she surveyed searched online for information on a loved one’s disease. Most looked for treatment options, prevention strategies and risk factors, and prognosis information.
“I was pleasantly surprised by the amount of people who said that they were looking for prevention information online and detection information,” Dr Lauckner said. “[T]hat shows that not only are they concerned for their loved one but they’re also concerned about how they themselves can avoid cancer, which, from a public health perspective, is great.”
Respondents were less inclined to view blogs or go online to hear about others’ cancer experiences. These kinds of sites were linked to negative emotions for participants, such as fear, sadness, and anger.
“A lot of people, especially in the cancer realm, they will use blogs or discussion posts to vent and to talk about the harsh realities of living with an illness,” Dr Lauckner said.
“And while I think that that is beneficial for both the person who is writing it and potentially for some people who want an idea of what to expect, when someone is dealing with the prospect of their loved one having to go through that experience, it can be extremely distressing.”
The most commonly visited websites were those of charitable organizations like the American Cancer Society, which were associated with positive emotions. Dr Lauckner said she found this information encouraging because it shows that participants were consulting reliable sources of information and not being swayed by personal accounts as much.
Dr Lauckner ultimately wants to build on the information gleaned in this study to determine the most effective use of social media and technology to distribute cancer prevention and risk reduction messages to the public.
chemotherapy
Photo by Rhoda Baer
Loved ones of cancer patients often turn to the Internet for further information about the disease, but they are less inclined to seek emotional support from social media forums, according to a study published in Computers, Informatics, Nursing.
It is fairly common for loved ones of cancer patients to develop depression or anxiety disorders as a result of the diagnosis, but there aren’t many studies focusing specifically on cancer patients’ caregivers and family members, said study author Carolyn Lauckner, PhD, of the University of Georgia in Athens.
“I think, sometimes, the loved ones and caregivers get forgotten about,” she said. “And that’s why I wanted to research this population to see if there are ways that we can better support these individuals.”
Dr Lauckner surveyed 191 people whose loved ones were diagnosed with cancer in the past year or who were currently acting as caregivers to someone with cancer. The motivation behind the research was personal for Dr Lauckner.
“I went through a period of time where I had 3 loved ones diagnosed within a short amount of time,” she said. “I had these experiences where I heard about the diagnosis and I would go online to look it up, and then I would immediately become terrified and freak out about all the stuff I read online.”
Like Dr Lauckner, more than 75% of the subjects she surveyed searched online for information on a loved one’s disease. Most looked for treatment options, prevention strategies and risk factors, and prognosis information.
“I was pleasantly surprised by the amount of people who said that they were looking for prevention information online and detection information,” Dr Lauckner said. “[T]hat shows that not only are they concerned for their loved one but they’re also concerned about how they themselves can avoid cancer, which, from a public health perspective, is great.”
Respondents were less inclined to view blogs or go online to hear about others’ cancer experiences. These kinds of sites were linked to negative emotions for participants, such as fear, sadness, and anger.
“A lot of people, especially in the cancer realm, they will use blogs or discussion posts to vent and to talk about the harsh realities of living with an illness,” Dr Lauckner said.
“And while I think that that is beneficial for both the person who is writing it and potentially for some people who want an idea of what to expect, when someone is dealing with the prospect of their loved one having to go through that experience, it can be extremely distressing.”
The most commonly visited websites were those of charitable organizations like the American Cancer Society, which were associated with positive emotions. Dr Lauckner said she found this information encouraging because it shows that participants were consulting reliable sources of information and not being swayed by personal accounts as much.
Dr Lauckner ultimately wants to build on the information gleaned in this study to determine the most effective use of social media and technology to distribute cancer prevention and risk reduction messages to the public.
chemotherapy
Photo by Rhoda Baer
Loved ones of cancer patients often turn to the Internet for further information about the disease, but they are less inclined to seek emotional support from social media forums, according to a study published in Computers, Informatics, Nursing.
It is fairly common for loved ones of cancer patients to develop depression or anxiety disorders as a result of the diagnosis, but there aren’t many studies focusing specifically on cancer patients’ caregivers and family members, said study author Carolyn Lauckner, PhD, of the University of Georgia in Athens.
“I think, sometimes, the loved ones and caregivers get forgotten about,” she said. “And that’s why I wanted to research this population to see if there are ways that we can better support these individuals.”
Dr Lauckner surveyed 191 people whose loved ones were diagnosed with cancer in the past year or who were currently acting as caregivers to someone with cancer. The motivation behind the research was personal for Dr Lauckner.
“I went through a period of time where I had 3 loved ones diagnosed within a short amount of time,” she said. “I had these experiences where I heard about the diagnosis and I would go online to look it up, and then I would immediately become terrified and freak out about all the stuff I read online.”
Like Dr Lauckner, more than 75% of the subjects she surveyed searched online for information on a loved one’s disease. Most looked for treatment options, prevention strategies and risk factors, and prognosis information.
“I was pleasantly surprised by the amount of people who said that they were looking for prevention information online and detection information,” Dr Lauckner said. “[T]hat shows that not only are they concerned for their loved one but they’re also concerned about how they themselves can avoid cancer, which, from a public health perspective, is great.”
Respondents were less inclined to view blogs or go online to hear about others’ cancer experiences. These kinds of sites were linked to negative emotions for participants, such as fear, sadness, and anger.
“A lot of people, especially in the cancer realm, they will use blogs or discussion posts to vent and to talk about the harsh realities of living with an illness,” Dr Lauckner said.
“And while I think that that is beneficial for both the person who is writing it and potentially for some people who want an idea of what to expect, when someone is dealing with the prospect of their loved one having to go through that experience, it can be extremely distressing.”
The most commonly visited websites were those of charitable organizations like the American Cancer Society, which were associated with positive emotions. Dr Lauckner said she found this information encouraging because it shows that participants were consulting reliable sources of information and not being swayed by personal accounts as much.
Dr Lauckner ultimately wants to build on the information gleaned in this study to determine the most effective use of social media and technology to distribute cancer prevention and risk reduction messages to the public.
Bile acid supports production of HSCs, team says
Photo by Åsa Hansdotter
Experiments in pregnant mice indicate that bile acid supports the production of hematopoietic stem cells (HSCs) in fetuses.
The work revealed large amounts of bile acids inside mouse fetuses and suggested these acids are transferred from the mothers via the placenta to help the fetuses produce HSCs.
“Fetuses produce small amounts of bile acids on their own, but here we are talking about much larger quantities,” said study author Kenichi Miharada, PhD, of Lund University in Sweden.
“The bile acid appears to be produced by the mother and then transferred to the fetus via the placenta.”
Dr Miharada and his colleagues detailed this discovery in Cell Stem Cell.
The investigators already knew that bile acid is produced in the fetal liver, but they did not know why.
With this study, they discovered that bile acid supports the production of HSCs in the fetal liver and enables them to develop normally. The additional contribution from the mother is important for the fetus to develop normally.
And although a large part of bile acid is toxic for cells, it undergoes a purification process when transferred through the placenta, letting only harmless bile acid through to the fetus.
“Our hypothesis is that the consequence of a damaged placenta, which, for various reasons, is unable to transfer bile acids to the fetus, can lead to leukemia or other blood diseases later in life, and we will continue our research to see if this hypothesis holds up,” Dr Miharada said.
He and his colleagues also said this work has implications for producing HSCs that could treat these blood diseases.
The problem with making HSCs proliferate outside the body is that the artificial growth gives rise to an accumulation of abnormal proteins in the endoplasmic reticulum (ER). This ER stress, if severe and chronic, causes cell death.
Dr Miharada and his colleagues previously showed it is possible to reduce ER stress chemically by adding bile acids to the cell culture. Bile acids, which are produced naturally in the liver and stored in the gallbladder, support protein production during the cell division process.
“Compared to other ways of trying to develop stem cells to treat blood diseases, this method is safer and quicker because it does not involve using any artificial substances or any genetic modifications, merely a substance that already exists inside the body,” Dr Miharada explained.
Photo by Åsa Hansdotter
Experiments in pregnant mice indicate that bile acid supports the production of hematopoietic stem cells (HSCs) in fetuses.
The work revealed large amounts of bile acids inside mouse fetuses and suggested these acids are transferred from the mothers via the placenta to help the fetuses produce HSCs.
“Fetuses produce small amounts of bile acids on their own, but here we are talking about much larger quantities,” said study author Kenichi Miharada, PhD, of Lund University in Sweden.
“The bile acid appears to be produced by the mother and then transferred to the fetus via the placenta.”
Dr Miharada and his colleagues detailed this discovery in Cell Stem Cell.
The investigators already knew that bile acid is produced in the fetal liver, but they did not know why.
With this study, they discovered that bile acid supports the production of HSCs in the fetal liver and enables them to develop normally. The additional contribution from the mother is important for the fetus to develop normally.
And although a large part of bile acid is toxic for cells, it undergoes a purification process when transferred through the placenta, letting only harmless bile acid through to the fetus.
“Our hypothesis is that the consequence of a damaged placenta, which, for various reasons, is unable to transfer bile acids to the fetus, can lead to leukemia or other blood diseases later in life, and we will continue our research to see if this hypothesis holds up,” Dr Miharada said.
He and his colleagues also said this work has implications for producing HSCs that could treat these blood diseases.
The problem with making HSCs proliferate outside the body is that the artificial growth gives rise to an accumulation of abnormal proteins in the endoplasmic reticulum (ER). This ER stress, if severe and chronic, causes cell death.
Dr Miharada and his colleagues previously showed it is possible to reduce ER stress chemically by adding bile acids to the cell culture. Bile acids, which are produced naturally in the liver and stored in the gallbladder, support protein production during the cell division process.
“Compared to other ways of trying to develop stem cells to treat blood diseases, this method is safer and quicker because it does not involve using any artificial substances or any genetic modifications, merely a substance that already exists inside the body,” Dr Miharada explained.
Photo by Åsa Hansdotter
Experiments in pregnant mice indicate that bile acid supports the production of hematopoietic stem cells (HSCs) in fetuses.
The work revealed large amounts of bile acids inside mouse fetuses and suggested these acids are transferred from the mothers via the placenta to help the fetuses produce HSCs.
“Fetuses produce small amounts of bile acids on their own, but here we are talking about much larger quantities,” said study author Kenichi Miharada, PhD, of Lund University in Sweden.
“The bile acid appears to be produced by the mother and then transferred to the fetus via the placenta.”
Dr Miharada and his colleagues detailed this discovery in Cell Stem Cell.
The investigators already knew that bile acid is produced in the fetal liver, but they did not know why.
With this study, they discovered that bile acid supports the production of HSCs in the fetal liver and enables them to develop normally. The additional contribution from the mother is important for the fetus to develop normally.
And although a large part of bile acid is toxic for cells, it undergoes a purification process when transferred through the placenta, letting only harmless bile acid through to the fetus.
“Our hypothesis is that the consequence of a damaged placenta, which, for various reasons, is unable to transfer bile acids to the fetus, can lead to leukemia or other blood diseases later in life, and we will continue our research to see if this hypothesis holds up,” Dr Miharada said.
He and his colleagues also said this work has implications for producing HSCs that could treat these blood diseases.
The problem with making HSCs proliferate outside the body is that the artificial growth gives rise to an accumulation of abnormal proteins in the endoplasmic reticulum (ER). This ER stress, if severe and chronic, causes cell death.
Dr Miharada and his colleagues previously showed it is possible to reduce ER stress chemically by adding bile acids to the cell culture. Bile acids, which are produced naturally in the liver and stored in the gallbladder, support protein production during the cell division process.
“Compared to other ways of trying to develop stem cells to treat blood diseases, this method is safer and quicker because it does not involve using any artificial substances or any genetic modifications, merely a substance that already exists inside the body,” Dr Miharada explained.
Group identifies SNPs associated with MBD
New research has revealed single-nucleotide polymorphisms (SNPs) that may increase the risk of bone disease in patients with multiple myeloma (MM).
One of these SNPs affects a gene encoding osteoprotegerin (OPG), a signaling protein that helps regulate the density of bones.
In patients with MM bone disease (MBD), bones are broken down faster than they can be repaired, resulting in fractures and lesions.
OPG is known to keep the numbers of osteoclasts in check, so it follows that mutations adversely affecting the gene may contribute to excessive bone breakdown.
Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK, and his colleagues reported these findings in Leukemia.
The researchers analyzed the DNA of 3774 MM patients and used imaging techniques to detect which of these patients had MBD and which did not. The team used statistical analysis to compare sequencing data from the group of patients who developed MBD with those who did not.
The analysis revealed 9 SNPs that showed an association with MBD and reached genome-wide significance. They were all located in the same region at 8q24.12 and were in strong linkage disequilibrium (LD).
The strongest association at 8q24.12 was observed with the SNP rs4407910, which localizes 19Kb 3’ to the gene encoding TNFRSF11B, also known as OPG (odds ratio=1.38, P=4.02×10−9).
The researchers also found a “promising association” for MBD with the SNP rs74676832 at 19q13.43, which is located within a 29 kb region of LD intergenic to ZNF444 and GALP (odds ratio=1.97, P=9.33×10–7).
The team said these findings demonstrate that germline variation influences MBD, and they highlight the importance of the RANK/RANKL/OPG pathway in MBD development.
Furthermore, the work could enable scientists to develop new strategies to prevent MBD development and identify which patients might benefit from treatment with existing bone therapies such as bisphosphonates.
“It is really important to understand why some patients with myeloma are severely affected by bone disease,” Dr Houlston said. “This study tells us that at least part of the answer is in the patient’s DNA, greatly improving our understanding of the disease.”
“We want to be able to identify which patients are most at risk and which treatments are most likely to help them. This study gives us clues that can begin to help us do this. In the longer term, understanding the factors that contributed to bone breakdown could help us find new treatments for the disease.”
New research has revealed single-nucleotide polymorphisms (SNPs) that may increase the risk of bone disease in patients with multiple myeloma (MM).
One of these SNPs affects a gene encoding osteoprotegerin (OPG), a signaling protein that helps regulate the density of bones.
In patients with MM bone disease (MBD), bones are broken down faster than they can be repaired, resulting in fractures and lesions.
OPG is known to keep the numbers of osteoclasts in check, so it follows that mutations adversely affecting the gene may contribute to excessive bone breakdown.
Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK, and his colleagues reported these findings in Leukemia.
The researchers analyzed the DNA of 3774 MM patients and used imaging techniques to detect which of these patients had MBD and which did not. The team used statistical analysis to compare sequencing data from the group of patients who developed MBD with those who did not.
The analysis revealed 9 SNPs that showed an association with MBD and reached genome-wide significance. They were all located in the same region at 8q24.12 and were in strong linkage disequilibrium (LD).
The strongest association at 8q24.12 was observed with the SNP rs4407910, which localizes 19Kb 3’ to the gene encoding TNFRSF11B, also known as OPG (odds ratio=1.38, P=4.02×10−9).
The researchers also found a “promising association” for MBD with the SNP rs74676832 at 19q13.43, which is located within a 29 kb region of LD intergenic to ZNF444 and GALP (odds ratio=1.97, P=9.33×10–7).
The team said these findings demonstrate that germline variation influences MBD, and they highlight the importance of the RANK/RANKL/OPG pathway in MBD development.
Furthermore, the work could enable scientists to develop new strategies to prevent MBD development and identify which patients might benefit from treatment with existing bone therapies such as bisphosphonates.
“It is really important to understand why some patients with myeloma are severely affected by bone disease,” Dr Houlston said. “This study tells us that at least part of the answer is in the patient’s DNA, greatly improving our understanding of the disease.”
“We want to be able to identify which patients are most at risk and which treatments are most likely to help them. This study gives us clues that can begin to help us do this. In the longer term, understanding the factors that contributed to bone breakdown could help us find new treatments for the disease.”
New research has revealed single-nucleotide polymorphisms (SNPs) that may increase the risk of bone disease in patients with multiple myeloma (MM).
One of these SNPs affects a gene encoding osteoprotegerin (OPG), a signaling protein that helps regulate the density of bones.
In patients with MM bone disease (MBD), bones are broken down faster than they can be repaired, resulting in fractures and lesions.
OPG is known to keep the numbers of osteoclasts in check, so it follows that mutations adversely affecting the gene may contribute to excessive bone breakdown.
Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK, and his colleagues reported these findings in Leukemia.
The researchers analyzed the DNA of 3774 MM patients and used imaging techniques to detect which of these patients had MBD and which did not. The team used statistical analysis to compare sequencing data from the group of patients who developed MBD with those who did not.
The analysis revealed 9 SNPs that showed an association with MBD and reached genome-wide significance. They were all located in the same region at 8q24.12 and were in strong linkage disequilibrium (LD).
The strongest association at 8q24.12 was observed with the SNP rs4407910, which localizes 19Kb 3’ to the gene encoding TNFRSF11B, also known as OPG (odds ratio=1.38, P=4.02×10−9).
The researchers also found a “promising association” for MBD with the SNP rs74676832 at 19q13.43, which is located within a 29 kb region of LD intergenic to ZNF444 and GALP (odds ratio=1.97, P=9.33×10–7).
The team said these findings demonstrate that germline variation influences MBD, and they highlight the importance of the RANK/RANKL/OPG pathway in MBD development.
Furthermore, the work could enable scientists to develop new strategies to prevent MBD development and identify which patients might benefit from treatment with existing bone therapies such as bisphosphonates.
“It is really important to understand why some patients with myeloma are severely affected by bone disease,” Dr Houlston said. “This study tells us that at least part of the answer is in the patient’s DNA, greatly improving our understanding of the disease.”
“We want to be able to identify which patients are most at risk and which treatments are most likely to help them. This study gives us clues that can begin to help us do this. In the longer term, understanding the factors that contributed to bone breakdown could help us find new treatments for the disease.”
Standard BMI inadequate for ALL patients
Photo by Bill Branson
New research suggests that body mass index (BMI) is an inadequate method for estimating changes in body fat and obesity in children with acute lymphoblastic leukemia (ALL).
Investigators found a discrepancy between BMI and body composition in this population, and the cause of this appeared to be increases in body fat with simultaneous loss of lean muscle mass during treatment.
The team reported these findings in Leukemia & Lymphoma.
With previous work, the investigators found that obese children diagnosed with high-risk ALL had a 50% greater risk of their disease recurring compared with children who were not obese.
“In my lab, we’ve seen a direct interaction between fat cells and leukemia cells that may help explain this increased risk of disease relapse,” said study author Steven Mittelman, MD, PhD, of Children’s Hospital Los Angeles in California.
“It appears that the fat cells ‘protect’ leukemia cells, making them less susceptible to chemotherapy and making an accurate measure of body fat essential.”
To determine if BMI accurately reflects body fat in ALL, the investigators analyzed 50 patients. They were predominantly Hispanic, between the ages of 10 to 21, and had newly diagnosed high-risk B-precursor ALL or T-cell ALL.
The team measured the percentage of total body fat and lean muscle mass at the time of diagnosis, at the end of induction, and at the end of delayed intensification. They also calculated BMI Z-score—a measure of how a given child’s BMI deviates from a population of children of the same age and sex—at these time points.
The investigators said sarcopenic obesity—gain in body fat percentage with loss of lean muscle mass—was “surprisingly common” during ALL treatment.
And sarcopenic obesity resulted in poor correlation between changes in BMI Z-score and body fat percentage overall (r=-0.05), within the time points (r=0.02), and within patients (r=-0.09, all not significant). BMI Z-score and body fat percentage changed in opposite directions in more than 50% of interval assessments.
“We found that change in BMI did not reflect changes in body fat or obesity,” said Etan Orgel, MD, of Children’s Hospital Los Angeles.
“In some patients, reaching a ‘healthy’ BMI was due solely to loss of muscle even while body fat continued to rise. Based on these results, we believe that evaluation of obesity in patients with leukemia should include direct measures of body composition.”
Photo by Bill Branson
New research suggests that body mass index (BMI) is an inadequate method for estimating changes in body fat and obesity in children with acute lymphoblastic leukemia (ALL).
Investigators found a discrepancy between BMI and body composition in this population, and the cause of this appeared to be increases in body fat with simultaneous loss of lean muscle mass during treatment.
The team reported these findings in Leukemia & Lymphoma.
With previous work, the investigators found that obese children diagnosed with high-risk ALL had a 50% greater risk of their disease recurring compared with children who were not obese.
“In my lab, we’ve seen a direct interaction between fat cells and leukemia cells that may help explain this increased risk of disease relapse,” said study author Steven Mittelman, MD, PhD, of Children’s Hospital Los Angeles in California.
“It appears that the fat cells ‘protect’ leukemia cells, making them less susceptible to chemotherapy and making an accurate measure of body fat essential.”
To determine if BMI accurately reflects body fat in ALL, the investigators analyzed 50 patients. They were predominantly Hispanic, between the ages of 10 to 21, and had newly diagnosed high-risk B-precursor ALL or T-cell ALL.
The team measured the percentage of total body fat and lean muscle mass at the time of diagnosis, at the end of induction, and at the end of delayed intensification. They also calculated BMI Z-score—a measure of how a given child’s BMI deviates from a population of children of the same age and sex—at these time points.
The investigators said sarcopenic obesity—gain in body fat percentage with loss of lean muscle mass—was “surprisingly common” during ALL treatment.
And sarcopenic obesity resulted in poor correlation between changes in BMI Z-score and body fat percentage overall (r=-0.05), within the time points (r=0.02), and within patients (r=-0.09, all not significant). BMI Z-score and body fat percentage changed in opposite directions in more than 50% of interval assessments.
“We found that change in BMI did not reflect changes in body fat or obesity,” said Etan Orgel, MD, of Children’s Hospital Los Angeles.
“In some patients, reaching a ‘healthy’ BMI was due solely to loss of muscle even while body fat continued to rise. Based on these results, we believe that evaluation of obesity in patients with leukemia should include direct measures of body composition.”
Photo by Bill Branson
New research suggests that body mass index (BMI) is an inadequate method for estimating changes in body fat and obesity in children with acute lymphoblastic leukemia (ALL).
Investigators found a discrepancy between BMI and body composition in this population, and the cause of this appeared to be increases in body fat with simultaneous loss of lean muscle mass during treatment.
The team reported these findings in Leukemia & Lymphoma.
With previous work, the investigators found that obese children diagnosed with high-risk ALL had a 50% greater risk of their disease recurring compared with children who were not obese.
“In my lab, we’ve seen a direct interaction between fat cells and leukemia cells that may help explain this increased risk of disease relapse,” said study author Steven Mittelman, MD, PhD, of Children’s Hospital Los Angeles in California.
“It appears that the fat cells ‘protect’ leukemia cells, making them less susceptible to chemotherapy and making an accurate measure of body fat essential.”
To determine if BMI accurately reflects body fat in ALL, the investigators analyzed 50 patients. They were predominantly Hispanic, between the ages of 10 to 21, and had newly diagnosed high-risk B-precursor ALL or T-cell ALL.
The team measured the percentage of total body fat and lean muscle mass at the time of diagnosis, at the end of induction, and at the end of delayed intensification. They also calculated BMI Z-score—a measure of how a given child’s BMI deviates from a population of children of the same age and sex—at these time points.
The investigators said sarcopenic obesity—gain in body fat percentage with loss of lean muscle mass—was “surprisingly common” during ALL treatment.
And sarcopenic obesity resulted in poor correlation between changes in BMI Z-score and body fat percentage overall (r=-0.05), within the time points (r=0.02), and within patients (r=-0.09, all not significant). BMI Z-score and body fat percentage changed in opposite directions in more than 50% of interval assessments.
“We found that change in BMI did not reflect changes in body fat or obesity,” said Etan Orgel, MD, of Children’s Hospital Los Angeles.
“In some patients, reaching a ‘healthy’ BMI was due solely to loss of muscle even while body fat continued to rise. Based on these results, we believe that evaluation of obesity in patients with leukemia should include direct measures of body composition.”
NICE issues draft guideline for NHL
a cancer patient
Photo courtesy of NCI/
Mathews Media Group
The National Institute for Health and Care Excellence (NICE) has issued a draft guideline for the diagnosis and management of non-Hodgkin lymphoma (NHL).
The guideline, which is open for consultation, covers adults and young people who are referred to secondary care with suspected NHL or who have newly diagnosed or relapsed NHL.
It contains recommendations for the management of 6 different NHL subtypes—diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, MALT lymphoma, Burkitt lymphoma, and peripheral T-cell lymphoma.
The guideline considers which method of biopsy is most appropriate, which diagnostic test most suitable, how the stage of disease is best assessed, and what treatment is likely to be most effective.
It also proposes recommendations for how best to support patients who complete their treatment. These include the provision of end-of-treatment summaries to be discussed with the patient and an increase in education on the possible relapse/late side-effects of their treatment.
“This draft guideline is now open for consultation,” said Mark Baker, director of the Centre of Clinical Practice at NICE.
“We want to hear from patients and all those who provide care for people with non-Hodgkin’s lymphoma in the NHS [National Health Service] so that we can produce a guideline which will support everyone who diagnoses, treats, and has to live with this disease.”
The consultation closes on March 11, 2016, with the final guideline expected in the summer.
a cancer patient
Photo courtesy of NCI/
Mathews Media Group
The National Institute for Health and Care Excellence (NICE) has issued a draft guideline for the diagnosis and management of non-Hodgkin lymphoma (NHL).
The guideline, which is open for consultation, covers adults and young people who are referred to secondary care with suspected NHL or who have newly diagnosed or relapsed NHL.
It contains recommendations for the management of 6 different NHL subtypes—diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, MALT lymphoma, Burkitt lymphoma, and peripheral T-cell lymphoma.
The guideline considers which method of biopsy is most appropriate, which diagnostic test most suitable, how the stage of disease is best assessed, and what treatment is likely to be most effective.
It also proposes recommendations for how best to support patients who complete their treatment. These include the provision of end-of-treatment summaries to be discussed with the patient and an increase in education on the possible relapse/late side-effects of their treatment.
“This draft guideline is now open for consultation,” said Mark Baker, director of the Centre of Clinical Practice at NICE.
“We want to hear from patients and all those who provide care for people with non-Hodgkin’s lymphoma in the NHS [National Health Service] so that we can produce a guideline which will support everyone who diagnoses, treats, and has to live with this disease.”
The consultation closes on March 11, 2016, with the final guideline expected in the summer.
a cancer patient
Photo courtesy of NCI/
Mathews Media Group
The National Institute for Health and Care Excellence (NICE) has issued a draft guideline for the diagnosis and management of non-Hodgkin lymphoma (NHL).
The guideline, which is open for consultation, covers adults and young people who are referred to secondary care with suspected NHL or who have newly diagnosed or relapsed NHL.
It contains recommendations for the management of 6 different NHL subtypes—diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, MALT lymphoma, Burkitt lymphoma, and peripheral T-cell lymphoma.
The guideline considers which method of biopsy is most appropriate, which diagnostic test most suitable, how the stage of disease is best assessed, and what treatment is likely to be most effective.
It also proposes recommendations for how best to support patients who complete their treatment. These include the provision of end-of-treatment summaries to be discussed with the patient and an increase in education on the possible relapse/late side-effects of their treatment.
“This draft guideline is now open for consultation,” said Mark Baker, director of the Centre of Clinical Practice at NICE.
“We want to hear from patients and all those who provide care for people with non-Hodgkin’s lymphoma in the NHS [National Health Service] so that we can produce a guideline which will support everyone who diagnoses, treats, and has to live with this disease.”
The consultation closes on March 11, 2016, with the final guideline expected in the summer.