Hematology Times

PHILADELPHIA—Internal medicine residents are obtaining transfusion consent from patients despite having poor knowledge of transfusion medicine, according to a study of nearly 500 residents in 9 countries.

On an exam assessing transfusion knowledge, the residents’ mean score was 45.7%.

And in a survey, an overwhelming majority of residents said they had “beginner” or “intermediate” transfusion knowledge.

Still, 89% said they had obtained patient consent for a transfusion.

Richard Haspel, MD, PhD, of Beth Israel Deacon Medical Center and Harvard Medical School in Boston, presented these data at the AABB Annual Meeting 2014 (abstract S45-030G).

“We all know there’s a problem with clinicians not knowing how to transfuse blood,” Dr Haspel began. “I would argue, though, that there are a lot of questions we don’t know the answer to. How prevalent is this problem? Are there some places that do it better than others? What areas need improvement?”

With these questions in mind, Dr Haspel and his colleagues used a 23-question survey and a 20-question exam (validated by the BEST Collaborative) to assess 474 internal medicine residents from 23 sites in 9 countries: Australia, Canada, England, Ireland, Italy, Germany, The Netherlands, Spain, and the US.

The mean score of correct responses in the exam was 45.7%. The mean score was significantly lower for first-year residents (43.9%) than for third- (47.1%; P=0.02) and fourth-year residents (50.6%, P=0.002).

However, as 50.6% was the highest mean score, exam scores were poor regardless of a resident’s time served, Dr Haspel noted. Scores were poor across the different study sites as well, ranging from about 32% to 55%.

The exam included questions on red cells, platelets, plasma, allergic reactions, transfusion-related acute lung injury (TRALI), and transfusion-associated circulatory overload (TACO), among other topics.

As an example, Dr Haspel pointed out that, for the 3 questions on TRALI, the percentage of correct responses did not exceed 15%. This was the topic about which residents seemed the least informed.

Dr Haspel noted that, in general, residents with more medical school hours spent learning about transfusion medicine and those with better perceived quality of their training tended to score higher on the exam. Still, there wasn’t much of a difference in exam scores between residents who said they had beginner, intermediate, or advanced knowledge of transfusion medicine.

Twelve percent of residents said they did not receive any transfusion medicine training in medical school, and 28% said they didn’t receive any training during their residency. About 35% said they received more than 2 hours of training in medical school, and 18% said they received more than 2 hours of training during their residency.

“In terms of the quality of the training, most rated it ‘slightly’ or ‘moderately’ effective,” Dr Haspel said. “In terms of attitudes and perceptions, most of them considered themselves a beginner [48%] or intermediate [48%] in regard to transfusion medicine knowledge.”

Ninety-seven percent of residents said they know how to contact the blood bank, and 72% said they know how to contact a transfusion medicine doctor. But 14% percent of residents did not know if their hospital had transfusion guidelines, and 1% wrongly said their hospital did not have guidelines.

Yet 89% of residents said they had obtained consent for a transfusion from a patient.

On the other hand, most residents (77%) said knowledge of transfusion medicine is “very” or “extremely” important in providing appropriate patient care. And 65% said they would find additional training “very” or “extremely” helpful.

PHILADELPHIA—Internal medicine residents are obtaining transfusion consent from patients despite having poor knowledge of transfusion medicine, according to a study of nearly 500 residents in 9 countries.

On an exam assessing transfusion knowledge, the residents’ mean score was 45.7%.

And in a survey, an overwhelming majority of residents said they had “beginner” or “intermediate” transfusion knowledge.

Still, 89% said they had obtained patient consent for a transfusion.

Richard Haspel, MD, PhD, of Beth Israel Deacon Medical Center and Harvard Medical School in Boston, presented these data at the AABB Annual Meeting 2014 (abstract S45-030G).

“We all know there’s a problem with clinicians not knowing how to transfuse blood,” Dr Haspel began. “I would argue, though, that there are a lot of questions we don’t know the answer to. How prevalent is this problem? Are there some places that do it better than others? What areas need improvement?”

With these questions in mind, Dr Haspel and his colleagues used a 23-question survey and a 20-question exam (validated by the BEST Collaborative) to assess 474 internal medicine residents from 23 sites in 9 countries: Australia, Canada, England, Ireland, Italy, Germany, The Netherlands, Spain, and the US.

The mean score of correct responses in the exam was 45.7%. The mean score was significantly lower for first-year residents (43.9%) than for third- (47.1%; P=0.02) and fourth-year residents (50.6%, P=0.002).

However, as 50.6% was the highest mean score, exam scores were poor regardless of a resident’s time served, Dr Haspel noted. Scores were poor across the different study sites as well, ranging from about 32% to 55%.

The exam included questions on red cells, platelets, plasma, allergic reactions, transfusion-related acute lung injury (TRALI), and transfusion-associated circulatory overload (TACO), among other topics.

As an example, Dr Haspel pointed out that, for the 3 questions on TRALI, the percentage of correct responses did not exceed 15%. This was the topic about which residents seemed the least informed.

Dr Haspel noted that, in general, residents with more medical school hours spent learning about transfusion medicine and those with better perceived quality of their training tended to score higher on the exam. Still, there wasn’t much of a difference in exam scores between residents who said they had beginner, intermediate, or advanced knowledge of transfusion medicine.

Twelve percent of residents said they did not receive any transfusion medicine training in medical school, and 28% said they didn’t receive any training during their residency. About 35% said they received more than 2 hours of training in medical school, and 18% said they received more than 2 hours of training during their residency.

“In terms of the quality of the training, most rated it ‘slightly’ or ‘moderately’ effective,” Dr Haspel said. “In terms of attitudes and perceptions, most of them considered themselves a beginner [48%] or intermediate [48%] in regard to transfusion medicine knowledge.”

Ninety-seven percent of residents said they know how to contact the blood bank, and 72% said they know how to contact a transfusion medicine doctor. But 14% percent of residents did not know if their hospital had transfusion guidelines, and 1% wrongly said their hospital did not have guidelines.

Yet 89% of residents said they had obtained consent for a transfusion from a patient.

On the other hand, most residents (77%) said knowledge of transfusion medicine is “very” or “extremely” important in providing appropriate patient care. And 65% said they would find additional training “very” or “extremely” helpful.

PHILADELPHIA—Internal medicine residents are obtaining transfusion consent from patients despite having poor knowledge of transfusion medicine, according to a study of nearly 500 residents in 9 countries.

On an exam assessing transfusion knowledge, the residents’ mean score was 45.7%.

And in a survey, an overwhelming majority of residents said they had “beginner” or “intermediate” transfusion knowledge.

Still, 89% said they had obtained patient consent for a transfusion.

Richard Haspel, MD, PhD, of Beth Israel Deacon Medical Center and Harvard Medical School in Boston, presented these data at the AABB Annual Meeting 2014 (abstract S45-030G).

“We all know there’s a problem with clinicians not knowing how to transfuse blood,” Dr Haspel began. “I would argue, though, that there are a lot of questions we don’t know the answer to. How prevalent is this problem? Are there some places that do it better than others? What areas need improvement?”

With these questions in mind, Dr Haspel and his colleagues used a 23-question survey and a 20-question exam (validated by the BEST Collaborative) to assess 474 internal medicine residents from 23 sites in 9 countries: Australia, Canada, England, Ireland, Italy, Germany, The Netherlands, Spain, and the US.

The mean score of correct responses in the exam was 45.7%. The mean score was significantly lower for first-year residents (43.9%) than for third- (47.1%; P=0.02) and fourth-year residents (50.6%, P=0.002).

However, as 50.6% was the highest mean score, exam scores were poor regardless of a resident’s time served, Dr Haspel noted. Scores were poor across the different study sites as well, ranging from about 32% to 55%.

The exam included questions on red cells, platelets, plasma, allergic reactions, transfusion-related acute lung injury (TRALI), and transfusion-associated circulatory overload (TACO), among other topics.

As an example, Dr Haspel pointed out that, for the 3 questions on TRALI, the percentage of correct responses did not exceed 15%. This was the topic about which residents seemed the least informed.

Dr Haspel noted that, in general, residents with more medical school hours spent learning about transfusion medicine and those with better perceived quality of their training tended to score higher on the exam. Still, there wasn’t much of a difference in exam scores between residents who said they had beginner, intermediate, or advanced knowledge of transfusion medicine.

Twelve percent of residents said they did not receive any transfusion medicine training in medical school, and 28% said they didn’t receive any training during their residency. About 35% said they received more than 2 hours of training in medical school, and 18% said they received more than 2 hours of training during their residency.

“In terms of the quality of the training, most rated it ‘slightly’ or ‘moderately’ effective,” Dr Haspel said. “In terms of attitudes and perceptions, most of them considered themselves a beginner [48%] or intermediate [48%] in regard to transfusion medicine knowledge.”

Ninety-seven percent of residents said they know how to contact the blood bank, and 72% said they know how to contact a transfusion medicine doctor. But 14% percent of residents did not know if their hospital had transfusion guidelines, and 1% wrongly said their hospital did not have guidelines.

Yet 89% of residents said they had obtained consent for a transfusion from a patient.

On the other hand, most residents (77%) said knowledge of transfusion medicine is “very” or “extremely” important in providing appropriate patient care. And 65% said they would find additional training “very” or “extremely” helpful.

Lab mice

Credit: Aaron Logan

A new method of genome editing can cure hemophilia B in mice, researchers have reported in Nature.

This new technique doesn’t require the co-delivery of an endonuclease to clip the recipient’s DNA at specific locations, and it doesn’t rely on the co-insertion of genetic promoters to activate the new gene’s expression.

These differences may make the new approach both safer and longer-lasting than other genome editing methods, according to researchers.

“It appears that we may be able to achieve lifelong expression of the inserted gene, which is particularly important when treating genetic diseases like hemophilia and severe combined immunodeficiency,” said study author Mark Kay, MD, PhD, of the Stanford University School of Medicine in California.

“We’re able to do this without using promoters or nucleases, which significantly reduces the chances of cancers that can result if the new gene inserts itself at random places in the genome.”

Using their new technique, Dr Kay and his colleagues were able to insert a working copy of the human coagulation factor IX gene into the DNA of mice with hemophilia B. Although the insertion was accomplished in only about 1% of liver cells, those cells made enough factor IX to ameliorate the disorder.

Instead of using nucleases to cut the DNA or a promoter to drive expression of the factor IX gene, the researchers hitched the expression of the new gene to that of albumin.

They used a modified version of adeno-associated virus and relied on homologous recombination to insert the factor IX gene near the albumin gene.

Using a special DNA linker between the genes, the researchers were able to ensure that the clotting factor protein was made hand-in-hand with the highly expressed albumin protein.

During homologous recombination, the cell takes advantage of the fact that it has two copies of every chromosome. By lining up the damaged and undamaged chromosomes, the cell can “crib” off the intact copy to repair the damage without losing vital genetic information.

The researchers used this natural process to copy sequences from the viral vector into the genome at places they chose—in this case, after the albumin gene.

When they tested their approach in newborn lab mice with hemophilia, the team found the animals began to express levels of factor IX that were between 7% and 20% of normal. That amount of clotting factor has been shown in previous studies to be therapeutic in mice.

The researchers further showed that the technique worked as well in adult animals, even though the gene was successfully inserted in fewer than 1 in every 100 liver cells.

“We expected this approach to work best in newborn animals because the liver is still growing,” Dr Kay said. “However, because homologous recombination has been thought to occur mostly in proliferating cells, we didn’t expect it to work as well as it did in adult animals.”

The researchers are now planning to test the technique in mice with livers composed of human and mouse cells, a model that may be a good surrogate to further predict what will happen in humans.

Lab mice

Credit: Aaron Logan

A new method of genome editing can cure hemophilia B in mice, researchers have reported in Nature.

This new technique doesn’t require the co-delivery of an endonuclease to clip the recipient’s DNA at specific locations, and it doesn’t rely on the co-insertion of genetic promoters to activate the new gene’s expression.

These differences may make the new approach both safer and longer-lasting than other genome editing methods, according to researchers.

“It appears that we may be able to achieve lifelong expression of the inserted gene, which is particularly important when treating genetic diseases like hemophilia and severe combined immunodeficiency,” said study author Mark Kay, MD, PhD, of the Stanford University School of Medicine in California.

“We’re able to do this without using promoters or nucleases, which significantly reduces the chances of cancers that can result if the new gene inserts itself at random places in the genome.”

Using their new technique, Dr Kay and his colleagues were able to insert a working copy of the human coagulation factor IX gene into the DNA of mice with hemophilia B. Although the insertion was accomplished in only about 1% of liver cells, those cells made enough factor IX to ameliorate the disorder.

Instead of using nucleases to cut the DNA or a promoter to drive expression of the factor IX gene, the researchers hitched the expression of the new gene to that of albumin.

They used a modified version of adeno-associated virus and relied on homologous recombination to insert the factor IX gene near the albumin gene.

Using a special DNA linker between the genes, the researchers were able to ensure that the clotting factor protein was made hand-in-hand with the highly expressed albumin protein.

During homologous recombination, the cell takes advantage of the fact that it has two copies of every chromosome. By lining up the damaged and undamaged chromosomes, the cell can “crib” off the intact copy to repair the damage without losing vital genetic information.

The researchers used this natural process to copy sequences from the viral vector into the genome at places they chose—in this case, after the albumin gene.

When they tested their approach in newborn lab mice with hemophilia, the team found the animals began to express levels of factor IX that were between 7% and 20% of normal. That amount of clotting factor has been shown in previous studies to be therapeutic in mice.

The researchers further showed that the technique worked as well in adult animals, even though the gene was successfully inserted in fewer than 1 in every 100 liver cells.

“We expected this approach to work best in newborn animals because the liver is still growing,” Dr Kay said. “However, because homologous recombination has been thought to occur mostly in proliferating cells, we didn’t expect it to work as well as it did in adult animals.”

The researchers are now planning to test the technique in mice with livers composed of human and mouse cells, a model that may be a good surrogate to further predict what will happen in humans.

Lab mice

Credit: Aaron Logan

A new method of genome editing can cure hemophilia B in mice, researchers have reported in Nature.

This new technique doesn’t require the co-delivery of an endonuclease to clip the recipient’s DNA at specific locations, and it doesn’t rely on the co-insertion of genetic promoters to activate the new gene’s expression.

These differences may make the new approach both safer and longer-lasting than other genome editing methods, according to researchers.

“It appears that we may be able to achieve lifelong expression of the inserted gene, which is particularly important when treating genetic diseases like hemophilia and severe combined immunodeficiency,” said study author Mark Kay, MD, PhD, of the Stanford University School of Medicine in California.

“We’re able to do this without using promoters or nucleases, which significantly reduces the chances of cancers that can result if the new gene inserts itself at random places in the genome.”

Using their new technique, Dr Kay and his colleagues were able to insert a working copy of the human coagulation factor IX gene into the DNA of mice with hemophilia B. Although the insertion was accomplished in only about 1% of liver cells, those cells made enough factor IX to ameliorate the disorder.

Instead of using nucleases to cut the DNA or a promoter to drive expression of the factor IX gene, the researchers hitched the expression of the new gene to that of albumin.

They used a modified version of adeno-associated virus and relied on homologous recombination to insert the factor IX gene near the albumin gene.

Using a special DNA linker between the genes, the researchers were able to ensure that the clotting factor protein was made hand-in-hand with the highly expressed albumin protein.

During homologous recombination, the cell takes advantage of the fact that it has two copies of every chromosome. By lining up the damaged and undamaged chromosomes, the cell can “crib” off the intact copy to repair the damage without losing vital genetic information.

The researchers used this natural process to copy sequences from the viral vector into the genome at places they chose—in this case, after the albumin gene.

When they tested their approach in newborn lab mice with hemophilia, the team found the animals began to express levels of factor IX that were between 7% and 20% of normal. That amount of clotting factor has been shown in previous studies to be therapeutic in mice.

The researchers further showed that the technique worked as well in adult animals, even though the gene was successfully inserted in fewer than 1 in every 100 liver cells.

“We expected this approach to work best in newborn animals because the liver is still growing,” Dr Kay said. “However, because homologous recombination has been thought to occur mostly in proliferating cells, we didn’t expect it to work as well as it did in adult animals.”

The researchers are now planning to test the technique in mice with livers composed of human and mouse cells, a model that may be a good surrogate to further predict what will happen in humans.

Myron S. Czuczman, MD

NEW YORK—With both the pro and con positions drawing on data from the phase 3 CLL11 trial, two speakers at the Lymphoma & Myeloma2014 congress faced off on whether it’s necessary to use chlorambucil with obinutuzumab in untreated chronic lymphocytic leukemia (CLL).

Myron S. Czuczman, MD, of Roswell Park Cancer Institute in Buffalo, New York, argued in favor of using chlorambucil. And Richard R. Furman, MD, of Weill Cornell Medical College in New York, argued against it.

Obinutuzumab is a glycoengineered, humanized, monoclonal antibody that selectively binds to the extracellular domain of the CD20 antigen on B cells.

It was approved by the US Food and Drug Administration based on initial results from the phase 3 CLL11 study, in which 781 patients were randomized to receive chlorambucil alone or chlorambucil with either obinutuzumab or rituximab.

Pro

Dr Czuczman pointed out that while the obinutuzumab-chlorambucil combination had more toxicity than the rituximab-chlorambucil combination, the overall response rate and complete response rate with obinutuzumab were significantly higher than with rituximab (P<0.0001).

Progression-free survival (PFS), which was the primary endpoint, was significantly higher with either obinutuzumab at 26.7 months, or rituximab, at 16.3 months, than with chlorambucil alone, at 11.1 months.

And in the head-to-head portion of CLL11, PFS with obinutuzumab-chlorambucil was significantly better at 26.7 months than with rituximab-chlorambucil, at 15.2 months (P<0.001).

Dr Czuczman also reviewed data on obinutuzumab combined with drugs other than chlorambucil.

The GALTON trial, a small, phase 1b trial in untreated CLL, compared obinutuzumab plus fludarabine and cyclophosphamide to obinutuzumab plus bendamustine.

Dr Czuczman showed that while there is more toxicity when obinutuzumab is combined with cyclophosphamide or bendamustine than with chlorambucil, “there is not much more activity.”

He said it’s not clear whether obinutuzumab with cyclophosphamide is better than rituximab with cyclophosphamide or if obinutuzumab with bendamustine is better than rituximab with bendamustine in upfront CLL.

“For now,” he said, “chloramubucil should be the only chemo agent combined with obinutuzumab to treat upfront CLL—outside of clinical trial participation.”

Con

Dr Furman also reviewed the CLL11 trial, noting that rituximab did not add very much to chlorambucil, but obinutuzumab did, in terms of overall survival and PFS. He cautioned, however, that additive or synergistic effects cannot be ruled out in the combination studies.

He then reviewed the GAGE trial, which compared 2 doses of single-agent obinutuzumab in untreated CLL. The 2000 mg dose produced a greater overall response rate than the 1000 mg dose, but the difference between the 2 arms was not significant (P=0.08).

PFS was 21 months in the 1000 mg arm and 20 months in the 2000 mg arm (P=0.07). PFS for obinutuzumab plus chlorambucil in the CLL11 trial was 26.7 months.

However, second cancers may be more of an issue with chlorambucil. In CALGB 9011, investigators reported 27 epithelial cancers, 9 with fludarabine, 11 with chlorambucil, and 7 with fludarabine plus chlorambucil.

Dr Furman concluded that while chlorambucil may aid obinutuzumab by reducing bulk, it may be unnecessary if higher doses of the antibody are used. Single-agent obinutuzumab produces a similar PFS as the combination with chlorambucil, and there are greater toxicities with chlorambucil.

Myron S. Czuczman, MD

NEW YORK—With both the pro and con positions drawing on data from the phase 3 CLL11 trial, two speakers at the Lymphoma & Myeloma2014 congress faced off on whether it’s necessary to use chlorambucil with obinutuzumab in untreated chronic lymphocytic leukemia (CLL).

Myron S. Czuczman, MD, of Roswell Park Cancer Institute in Buffalo, New York, argued in favor of using chlorambucil. And Richard R. Furman, MD, of Weill Cornell Medical College in New York, argued against it.

Obinutuzumab is a glycoengineered, humanized, monoclonal antibody that selectively binds to the extracellular domain of the CD20 antigen on B cells.

It was approved by the US Food and Drug Administration based on initial results from the phase 3 CLL11 study, in which 781 patients were randomized to receive chlorambucil alone or chlorambucil with either obinutuzumab or rituximab.

Pro

Dr Czuczman pointed out that while the obinutuzumab-chlorambucil combination had more toxicity than the rituximab-chlorambucil combination, the overall response rate and complete response rate with obinutuzumab were significantly higher than with rituximab (P<0.0001).

Progression-free survival (PFS), which was the primary endpoint, was significantly higher with either obinutuzumab at 26.7 months, or rituximab, at 16.3 months, than with chlorambucil alone, at 11.1 months.

And in the head-to-head portion of CLL11, PFS with obinutuzumab-chlorambucil was significantly better at 26.7 months than with rituximab-chlorambucil, at 15.2 months (P<0.001).

Dr Czuczman also reviewed data on obinutuzumab combined with drugs other than chlorambucil.

The GALTON trial, a small, phase 1b trial in untreated CLL, compared obinutuzumab plus fludarabine and cyclophosphamide to obinutuzumab plus bendamustine.

Dr Czuczman showed that while there is more toxicity when obinutuzumab is combined with cyclophosphamide or bendamustine than with chlorambucil, “there is not much more activity.”

He said it’s not clear whether obinutuzumab with cyclophosphamide is better than rituximab with cyclophosphamide or if obinutuzumab with bendamustine is better than rituximab with bendamustine in upfront CLL.

“For now,” he said, “chloramubucil should be the only chemo agent combined with obinutuzumab to treat upfront CLL—outside of clinical trial participation.”

Con

Dr Furman also reviewed the CLL11 trial, noting that rituximab did not add very much to chlorambucil, but obinutuzumab did, in terms of overall survival and PFS. He cautioned, however, that additive or synergistic effects cannot be ruled out in the combination studies.

He then reviewed the GAGE trial, which compared 2 doses of single-agent obinutuzumab in untreated CLL. The 2000 mg dose produced a greater overall response rate than the 1000 mg dose, but the difference between the 2 arms was not significant (P=0.08).

PFS was 21 months in the 1000 mg arm and 20 months in the 2000 mg arm (P=0.07). PFS for obinutuzumab plus chlorambucil in the CLL11 trial was 26.7 months.

However, second cancers may be more of an issue with chlorambucil. In CALGB 9011, investigators reported 27 epithelial cancers, 9 with fludarabine, 11 with chlorambucil, and 7 with fludarabine plus chlorambucil.

Dr Furman concluded that while chlorambucil may aid obinutuzumab by reducing bulk, it may be unnecessary if higher doses of the antibody are used. Single-agent obinutuzumab produces a similar PFS as the combination with chlorambucil, and there are greater toxicities with chlorambucil.

Myron S. Czuczman, MD

NEW YORK—With both the pro and con positions drawing on data from the phase 3 CLL11 trial, two speakers at the Lymphoma & Myeloma2014 congress faced off on whether it’s necessary to use chlorambucil with obinutuzumab in untreated chronic lymphocytic leukemia (CLL).

Myron S. Czuczman, MD, of Roswell Park Cancer Institute in Buffalo, New York, argued in favor of using chlorambucil. And Richard R. Furman, MD, of Weill Cornell Medical College in New York, argued against it.

Obinutuzumab is a glycoengineered, humanized, monoclonal antibody that selectively binds to the extracellular domain of the CD20 antigen on B cells.

It was approved by the US Food and Drug Administration based on initial results from the phase 3 CLL11 study, in which 781 patients were randomized to receive chlorambucil alone or chlorambucil with either obinutuzumab or rituximab.

Pro

Dr Czuczman pointed out that while the obinutuzumab-chlorambucil combination had more toxicity than the rituximab-chlorambucil combination, the overall response rate and complete response rate with obinutuzumab were significantly higher than with rituximab (P<0.0001).

Progression-free survival (PFS), which was the primary endpoint, was significantly higher with either obinutuzumab at 26.7 months, or rituximab, at 16.3 months, than with chlorambucil alone, at 11.1 months.

And in the head-to-head portion of CLL11, PFS with obinutuzumab-chlorambucil was significantly better at 26.7 months than with rituximab-chlorambucil, at 15.2 months (P<0.001).

Dr Czuczman also reviewed data on obinutuzumab combined with drugs other than chlorambucil.

The GALTON trial, a small, phase 1b trial in untreated CLL, compared obinutuzumab plus fludarabine and cyclophosphamide to obinutuzumab plus bendamustine.

Dr Czuczman showed that while there is more toxicity when obinutuzumab is combined with cyclophosphamide or bendamustine than with chlorambucil, “there is not much more activity.”

He said it’s not clear whether obinutuzumab with cyclophosphamide is better than rituximab with cyclophosphamide or if obinutuzumab with bendamustine is better than rituximab with bendamustine in upfront CLL.

“For now,” he said, “chloramubucil should be the only chemo agent combined with obinutuzumab to treat upfront CLL—outside of clinical trial participation.”

Con

Dr Furman also reviewed the CLL11 trial, noting that rituximab did not add very much to chlorambucil, but obinutuzumab did, in terms of overall survival and PFS. He cautioned, however, that additive or synergistic effects cannot be ruled out in the combination studies.

He then reviewed the GAGE trial, which compared 2 doses of single-agent obinutuzumab in untreated CLL. The 2000 mg dose produced a greater overall response rate than the 1000 mg dose, but the difference between the 2 arms was not significant (P=0.08).

PFS was 21 months in the 1000 mg arm and 20 months in the 2000 mg arm (P=0.07). PFS for obinutuzumab plus chlorambucil in the CLL11 trial was 26.7 months.

However, second cancers may be more of an issue with chlorambucil. In CALGB 9011, investigators reported 27 epithelial cancers, 9 with fludarabine, 11 with chlorambucil, and 7 with fludarabine plus chlorambucil.

Dr Furman concluded that while chlorambucil may aid obinutuzumab by reducing bulk, it may be unnecessary if higher doses of the antibody are used. Single-agent obinutuzumab produces a similar PFS as the combination with chlorambucil, and there are greater toxicities with chlorambucil.

Doctor with clipboard

A survey of nearly 5000 US physicians showed that the average doctor spent 16.6% of his or her working hours on non-patient-related paperwork.

This includes tasks such as billing, obtaining insurance approvals, financial and personnel management, and negotiating contracts.

The more time doctors spent on such tasks, the less satisfied they were with medicine as a career.

Researchers detailed these findings in the International Journal of Health Services.

“Our crazy health financing system is demoralizing doctors and wasting vast resources,” said study author David Himmelstein, MD, a professor at Hunter College of the City University of New York.

“Turning healthcare into a business means we spend more and more time on billing, insurance paperwork, and the bottom line. We need to move to a simple, nonprofit national health insurance system that lets doctors and hospitals focus on patients, not finances.”

Dr Himmelstein and colleague Steffie Woolhandler, MD, analyzed confidential data from the 2008 Health Tracking Physician Survey (the most recent data available). The survey included information from a nationally representative sample of 4720 physicians who practiced at least 20 hours per week.

The data showed that the average doctor spent 8.7 hours per week, or 16.6% of his or her working time, on non-patient-related administration. This excludes tasks such as writing chart notes, communicating with other doctors, and ordering lab tests.

In total, patient-care physicians spent 168.4 million hours on non-patient-related administrative tasks in 2008. Drs Himmelstein and Woolhandler estimate that the total cost of physician time spent on administration in 2014 will amount to $102 billion.

Career satisfaction was lower for physicians who spent more time on administration. “Very satisfied” doctors spent, on average, 16.1% of their time on administration. “Very dissatisfied” doctors spent 20.6% of their time on such tasks.

Among various specialties, psychiatrists spent the most time on administration (20.3%), followed by internists (17.3%) and family/general practitioners (17.3%). Pediatricians spent the least amount of time (14.1%) on non-patient-related administrative tasks and were the most satisfied group of doctors.

Solo practice was associated with more administrative work, but small group practice was not. Doctors practicing in groups of 100 or more actually spent more time (19.7%) on such tasks than those in small groups (16.3%).

The researchers were surprised to find that physicians who used electronic health records spent more time (17.2% for those using entirely electronic records, 18% for those using a mix of paper and electronic) on administration than those who used only paper records (15.5%).

The pair noted that physicians in Canada spend far less time on administration than US doctors, and they attributed the difference to Canada’s single-payer system, which has greatly simplified billing and reduced bureaucracy.

The researchers pointed out that the only previous nationally representative survey of this kind was carried out in 1995, and that study showed that administration and insurance-related matters accounted for 13.5% of physicians’ total work time. Other, less representative studies also suggest the bureaucratic burden on physicians has grown in the past two decades.

“American doctors are drowning in paperwork,” Dr Woolhandler said. “Our study almost certainly understates physicians’ current administrative burden.”

“Since 2008, when the survey we analyzed was collected, tens of thousands of doctors have moved from small private practices with minimal bureaucracy into giant group practices where bureaucracy is rampant. And under the accountable care organizations favored by insurers, more doctors are facing HMO-type incentives to deny care to their patients, a move that our data shows drives up administrative work.”

Doctor with clipboard

A survey of nearly 5000 US physicians showed that the average doctor spent 16.6% of his or her working hours on non-patient-related paperwork.

This includes tasks such as billing, obtaining insurance approvals, financial and personnel management, and negotiating contracts.

The more time doctors spent on such tasks, the less satisfied they were with medicine as a career.

Researchers detailed these findings in the International Journal of Health Services.

“Our crazy health financing system is demoralizing doctors and wasting vast resources,” said study author David Himmelstein, MD, a professor at Hunter College of the City University of New York.

“Turning healthcare into a business means we spend more and more time on billing, insurance paperwork, and the bottom line. We need to move to a simple, nonprofit national health insurance system that lets doctors and hospitals focus on patients, not finances.”

Dr Himmelstein and colleague Steffie Woolhandler, MD, analyzed confidential data from the 2008 Health Tracking Physician Survey (the most recent data available). The survey included information from a nationally representative sample of 4720 physicians who practiced at least 20 hours per week.

The data showed that the average doctor spent 8.7 hours per week, or 16.6% of his or her working time, on non-patient-related administration. This excludes tasks such as writing chart notes, communicating with other doctors, and ordering lab tests.

In total, patient-care physicians spent 168.4 million hours on non-patient-related administrative tasks in 2008. Drs Himmelstein and Woolhandler estimate that the total cost of physician time spent on administration in 2014 will amount to $102 billion.

Career satisfaction was lower for physicians who spent more time on administration. “Very satisfied” doctors spent, on average, 16.1% of their time on administration. “Very dissatisfied” doctors spent 20.6% of their time on such tasks.

Among various specialties, psychiatrists spent the most time on administration (20.3%), followed by internists (17.3%) and family/general practitioners (17.3%). Pediatricians spent the least amount of time (14.1%) on non-patient-related administrative tasks and were the most satisfied group of doctors.

Solo practice was associated with more administrative work, but small group practice was not. Doctors practicing in groups of 100 or more actually spent more time (19.7%) on such tasks than those in small groups (16.3%).

The researchers were surprised to find that physicians who used electronic health records spent more time (17.2% for those using entirely electronic records, 18% for those using a mix of paper and electronic) on administration than those who used only paper records (15.5%).

The pair noted that physicians in Canada spend far less time on administration than US doctors, and they attributed the difference to Canada’s single-payer system, which has greatly simplified billing and reduced bureaucracy.

The researchers pointed out that the only previous nationally representative survey of this kind was carried out in 1995, and that study showed that administration and insurance-related matters accounted for 13.5% of physicians’ total work time. Other, less representative studies also suggest the bureaucratic burden on physicians has grown in the past two decades.

“American doctors are drowning in paperwork,” Dr Woolhandler said. “Our study almost certainly understates physicians’ current administrative burden.”

“Since 2008, when the survey we analyzed was collected, tens of thousands of doctors have moved from small private practices with minimal bureaucracy into giant group practices where bureaucracy is rampant. And under the accountable care organizations favored by insurers, more doctors are facing HMO-type incentives to deny care to their patients, a move that our data shows drives up administrative work.”

Doctor with clipboard

A survey of nearly 5000 US physicians showed that the average doctor spent 16.6% of his or her working hours on non-patient-related paperwork.

This includes tasks such as billing, obtaining insurance approvals, financial and personnel management, and negotiating contracts.

The more time doctors spent on such tasks, the less satisfied they were with medicine as a career.

Researchers detailed these findings in the International Journal of Health Services.

“Our crazy health financing system is demoralizing doctors and wasting vast resources,” said study author David Himmelstein, MD, a professor at Hunter College of the City University of New York.

“Turning healthcare into a business means we spend more and more time on billing, insurance paperwork, and the bottom line. We need to move to a simple, nonprofit national health insurance system that lets doctors and hospitals focus on patients, not finances.”

Dr Himmelstein and colleague Steffie Woolhandler, MD, analyzed confidential data from the 2008 Health Tracking Physician Survey (the most recent data available). The survey included information from a nationally representative sample of 4720 physicians who practiced at least 20 hours per week.

The data showed that the average doctor spent 8.7 hours per week, or 16.6% of his or her working time, on non-patient-related administration. This excludes tasks such as writing chart notes, communicating with other doctors, and ordering lab tests.

In total, patient-care physicians spent 168.4 million hours on non-patient-related administrative tasks in 2008. Drs Himmelstein and Woolhandler estimate that the total cost of physician time spent on administration in 2014 will amount to $102 billion.

Career satisfaction was lower for physicians who spent more time on administration. “Very satisfied” doctors spent, on average, 16.1% of their time on administration. “Very dissatisfied” doctors spent 20.6% of their time on such tasks.

Among various specialties, psychiatrists spent the most time on administration (20.3%), followed by internists (17.3%) and family/general practitioners (17.3%). Pediatricians spent the least amount of time (14.1%) on non-patient-related administrative tasks and were the most satisfied group of doctors.

Solo practice was associated with more administrative work, but small group practice was not. Doctors practicing in groups of 100 or more actually spent more time (19.7%) on such tasks than those in small groups (16.3%).

The researchers were surprised to find that physicians who used electronic health records spent more time (17.2% for those using entirely electronic records, 18% for those using a mix of paper and electronic) on administration than those who used only paper records (15.5%).

The pair noted that physicians in Canada spend far less time on administration than US doctors, and they attributed the difference to Canada’s single-payer system, which has greatly simplified billing and reduced bureaucracy.

The researchers pointed out that the only previous nationally representative survey of this kind was carried out in 1995, and that study showed that administration and insurance-related matters accounted for 13.5% of physicians’ total work time. Other, less representative studies also suggest the bureaucratic burden on physicians has grown in the past two decades.

“American doctors are drowning in paperwork,” Dr Woolhandler said. “Our study almost certainly understates physicians’ current administrative burden.”

“Since 2008, when the survey we analyzed was collected, tens of thousands of doctors have moved from small private practices with minimal bureaucracy into giant group practices where bureaucracy is rampant. And under the accountable care organizations favored by insurers, more doctors are facing HMO-type incentives to deny care to their patients, a move that our data shows drives up administrative work.”

Bone marrow biopsy

Credit: Chad McNeeley

The International Myeloma Working Group (IMWG) has published new criteria for diagnosing multiple myeloma (MM) in The Lancet Oncology.

The group has added validated biomarkers to the current clinical symptoms used for MM diagnosis—hypercalcemia, renal failure, anemia, and bone lesions.

This addition will allow physicians to diagnose MM before patients become symptomatic and, therefore, before organ damage occurs, according to the IMWG.

Lead author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota, noted that MM is always preceded sequentially by two conditions—monoclonal gammopathy of undetermined significance and smoldering MM. Since both are asymptomatic, most MM patients are not diagnosed until organ damage occurs.

“The new IMWG criteria allow for the diagnosis of myeloma to be made in patients without symptoms and before organ damage occurs, using validated biomarkers that identify patients with [smoldering] MM who have an ‘ultra-high’ risk of progression to multiple myeloma,” Dr Rajkumar said.

“These biomarkers are associated with the near-inevitable development of clinical symptoms and are important for early diagnosis and treatment, which is very important for patients.”

Other updates to the criteria used to diagnose MM include the use of CT and PET-CT scans to identify bone lesions. According to the authors, this will enable more accurate diagnosis and intervention before fractures or other serious problems arise.

“We believe that the new criteria will rectify the situation where we were unable to use the considerable advances in multiple myeloma therapy prior to organ damage,” Dr Rajkumar said. “We can now initiate therapy in some patients early on in the course of their disease.”

The IMWG’s revised diagnostic criteria for MM and smoldering MM are as follows.

Definition of MM

Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma* and one or more of the following myeloma defining events:

• Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:

  • Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL).
  • Renal insufficiency: creatinine clearance <40 mL per min (measured or estimated by validated equations) or serum creatinine >177 μmol/L (>2 mg/dL).
  • Anemia: hemoglobin value of >20 g/L below the lower limit of normal or a hemoglobin value <100 g/L.
  • Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT. If the bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement.

• One or more of the following biomarkers:

  • Clonal bone marrow plasma cell percentage ≥60%.
  • Involved:uninvolved serum free light chain ratio ≥100. These values are based on the serum Freelite assay (The Binding Site Group, Birmingham, UK). The involved free light chain must be ≥100 mg/L.
  • >1 focal lesions on MRI studies. Each focal lesion must be 5 mm or more in size.

*The IMWG said clonality should be established by showing κ/λ-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone

marrow plasma cell percentage should preferably be estimated from a core biopsy specimen. In case of a disparity between the aspirate and core biopsy, the highest value should be used.

Definition of smoldering MM

Both of the following criteria must be met:

• Serum monoclonal protein (IgG or IgA) ≥30 g/L or urinary monoclonal protein ≥500 mg per 24 hours and/or clonal bone marrow plasma cells 10%–60%.
• Absence of myeloma defining events or amyloidosis.
  

Bone marrow biopsy

Credit: Chad McNeeley

The International Myeloma Working Group (IMWG) has published new criteria for diagnosing multiple myeloma (MM) in The Lancet Oncology.

The group has added validated biomarkers to the current clinical symptoms used for MM diagnosis—hypercalcemia, renal failure, anemia, and bone lesions.

This addition will allow physicians to diagnose MM before patients become symptomatic and, therefore, before organ damage occurs, according to the IMWG.

Lead author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota, noted that MM is always preceded sequentially by two conditions—monoclonal gammopathy of undetermined significance and smoldering MM. Since both are asymptomatic, most MM patients are not diagnosed until organ damage occurs.

“The new IMWG criteria allow for the diagnosis of myeloma to be made in patients without symptoms and before organ damage occurs, using validated biomarkers that identify patients with [smoldering] MM who have an ‘ultra-high’ risk of progression to multiple myeloma,” Dr Rajkumar said.

“These biomarkers are associated with the near-inevitable development of clinical symptoms and are important for early diagnosis and treatment, which is very important for patients.”

Other updates to the criteria used to diagnose MM include the use of CT and PET-CT scans to identify bone lesions. According to the authors, this will enable more accurate diagnosis and intervention before fractures or other serious problems arise.

“We believe that the new criteria will rectify the situation where we were unable to use the considerable advances in multiple myeloma therapy prior to organ damage,” Dr Rajkumar said. “We can now initiate therapy in some patients early on in the course of their disease.”

The IMWG’s revised diagnostic criteria for MM and smoldering MM are as follows.

Definition of MM

Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma* and one or more of the following myeloma defining events:

• Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:

  • Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL).
  • Renal insufficiency: creatinine clearance <40 mL per min (measured or estimated by validated equations) or serum creatinine >177 μmol/L (>2 mg/dL).
  • Anemia: hemoglobin value of >20 g/L below the lower limit of normal or a hemoglobin value <100 g/L.
  • Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT. If the bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement.

• One or more of the following biomarkers:

  • Clonal bone marrow plasma cell percentage ≥60%.
  • Involved:uninvolved serum free light chain ratio ≥100. These values are based on the serum Freelite assay (The Binding Site Group, Birmingham, UK). The involved free light chain must be ≥100 mg/L.
  • >1 focal lesions on MRI studies. Each focal lesion must be 5 mm or more in size.

*The IMWG said clonality should be established by showing κ/λ-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone

marrow plasma cell percentage should preferably be estimated from a core biopsy specimen. In case of a disparity between the aspirate and core biopsy, the highest value should be used.

Definition of smoldering MM

Both of the following criteria must be met:

• Serum monoclonal protein (IgG or IgA) ≥30 g/L or urinary monoclonal protein ≥500 mg per 24 hours and/or clonal bone marrow plasma cells 10%–60%.
• Absence of myeloma defining events or amyloidosis.
  

Bone marrow biopsy

Credit: Chad McNeeley

The International Myeloma Working Group (IMWG) has published new criteria for diagnosing multiple myeloma (MM) in The Lancet Oncology.

The group has added validated biomarkers to the current clinical symptoms used for MM diagnosis—hypercalcemia, renal failure, anemia, and bone lesions.

This addition will allow physicians to diagnose MM before patients become symptomatic and, therefore, before organ damage occurs, according to the IMWG.

Lead author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota, noted that MM is always preceded sequentially by two conditions—monoclonal gammopathy of undetermined significance and smoldering MM. Since both are asymptomatic, most MM patients are not diagnosed until organ damage occurs.

“The new IMWG criteria allow for the diagnosis of myeloma to be made in patients without symptoms and before organ damage occurs, using validated biomarkers that identify patients with [smoldering] MM who have an ‘ultra-high’ risk of progression to multiple myeloma,” Dr Rajkumar said.

“These biomarkers are associated with the near-inevitable development of clinical symptoms and are important for early diagnosis and treatment, which is very important for patients.”

Other updates to the criteria used to diagnose MM include the use of CT and PET-CT scans to identify bone lesions. According to the authors, this will enable more accurate diagnosis and intervention before fractures or other serious problems arise.

“We believe that the new criteria will rectify the situation where we were unable to use the considerable advances in multiple myeloma therapy prior to organ damage,” Dr Rajkumar said. “We can now initiate therapy in some patients early on in the course of their disease.”

The IMWG’s revised diagnostic criteria for MM and smoldering MM are as follows.

Definition of MM

Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma* and one or more of the following myeloma defining events:

• Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:

  • Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL).
  • Renal insufficiency: creatinine clearance <40 mL per min (measured or estimated by validated equations) or serum creatinine >177 μmol/L (>2 mg/dL).
  • Anemia: hemoglobin value of >20 g/L below the lower limit of normal or a hemoglobin value <100 g/L.
  • Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT. If the bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement.

• One or more of the following biomarkers:

  • Clonal bone marrow plasma cell percentage ≥60%.
  • Involved:uninvolved serum free light chain ratio ≥100. These values are based on the serum Freelite assay (The Binding Site Group, Birmingham, UK). The involved free light chain must be ≥100 mg/L.
  • >1 focal lesions on MRI studies. Each focal lesion must be 5 mm or more in size.

*The IMWG said clonality should be established by showing κ/λ-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone

marrow plasma cell percentage should preferably be estimated from a core biopsy specimen. In case of a disparity between the aspirate and core biopsy, the highest value should be used.

Definition of smoldering MM

Both of the following criteria must be met:

• Serum monoclonal protein (IgG or IgA) ≥30 g/L or urinary monoclonal protein ≥500 mg per 24 hours and/or clonal bone marrow plasma cells 10%–60%.
• Absence of myeloma defining events or amyloidosis.
  

Blood sample collection

Credit: Juan D. Alfonso

A new device can measure methotrexate levels in a patient’s blood in less than a minute, according to research published in Biosensors and Bioelectronics.

Researchers say this nanoscale device is just as accurate and 10 times less expensive than equipment currently used in hospitals.

It has an optical system that can rapidly gauge the optimal dose of methotrexate a patient needs, thereby reducing the risk of adverse effects.

“While effective, methotrexate is also highly toxic and can damage the healthy cells of patients, hence the importance of closely monitoring the drug’s concentration in the serum of treated individuals to adjust the dosage,” said study author Jean François Masson, PhD, of the University of Montreal in Quebec, Canada.

“The operation of the current [methotrexate monitoring] device is based on a cumbersome, expensive platform that requires experienced personnel because of the many samples that need to be manipulated.”

With this in mind, Dr Masson and his colleagues set out to simplify methotrexate monitoring.

In the course of their research, the team developed and manufactured a miniaturized device that works by surface plasmon resonance. It measures the concentration of serum methotrexate through gold nanoparticles on the surface of a receptacle.

In “competing” with methotrexate to block the enzyme dihydrofolate reductase, the gold nanoparticles change the color of the light detected by the instrument. And the color of the light detected reflects the exact concentration of the drug in the blood sample.

The researchers compared the accuracy of measurements taken with the new device to those taken with equipment used at the Maisonneuve-Rosemont Hospital in Montreal.

“Testing was conclusive,” Dr Masson said. “Not only were the measurements as accurate, but our device took less than 60 seconds to produce results, compared to 30 minutes for current devices.”

Moreover, the comparative tests were performed by lab technicians who were not experienced with surface plasmon resonance and did not encounter major difficulties in operating the new equipment or obtaining the same conclusive results as Dr Masson and his research team.

“In the near future, we can foresee the device in doctors’ offices or even at the bedside, where patients would receive individualized and optimal doses while minimizing the risk of complications,” Dr Masson said.

“While traditional equipment requires an investment of around $100,000, the new mobile device would likely cost 10 times less, around $10,000.”

Blood sample collection

Credit: Juan D. Alfonso

A new device can measure methotrexate levels in a patient’s blood in less than a minute, according to research published in Biosensors and Bioelectronics.

Researchers say this nanoscale device is just as accurate and 10 times less expensive than equipment currently used in hospitals.

It has an optical system that can rapidly gauge the optimal dose of methotrexate a patient needs, thereby reducing the risk of adverse effects.

“While effective, methotrexate is also highly toxic and can damage the healthy cells of patients, hence the importance of closely monitoring the drug’s concentration in the serum of treated individuals to adjust the dosage,” said study author Jean François Masson, PhD, of the University of Montreal in Quebec, Canada.

“The operation of the current [methotrexate monitoring] device is based on a cumbersome, expensive platform that requires experienced personnel because of the many samples that need to be manipulated.”

With this in mind, Dr Masson and his colleagues set out to simplify methotrexate monitoring.

In the course of their research, the team developed and manufactured a miniaturized device that works by surface plasmon resonance. It measures the concentration of serum methotrexate through gold nanoparticles on the surface of a receptacle.

In “competing” with methotrexate to block the enzyme dihydrofolate reductase, the gold nanoparticles change the color of the light detected by the instrument. And the color of the light detected reflects the exact concentration of the drug in the blood sample.

The researchers compared the accuracy of measurements taken with the new device to those taken with equipment used at the Maisonneuve-Rosemont Hospital in Montreal.

“Testing was conclusive,” Dr Masson said. “Not only were the measurements as accurate, but our device took less than 60 seconds to produce results, compared to 30 minutes for current devices.”

Moreover, the comparative tests were performed by lab technicians who were not experienced with surface plasmon resonance and did not encounter major difficulties in operating the new equipment or obtaining the same conclusive results as Dr Masson and his research team.

“In the near future, we can foresee the device in doctors’ offices or even at the bedside, where patients would receive individualized and optimal doses while minimizing the risk of complications,” Dr Masson said.

“While traditional equipment requires an investment of around $100,000, the new mobile device would likely cost 10 times less, around $10,000.”

Blood sample collection

Credit: Juan D. Alfonso

A new device can measure methotrexate levels in a patient’s blood in less than a minute, according to research published in Biosensors and Bioelectronics.

Researchers say this nanoscale device is just as accurate and 10 times less expensive than equipment currently used in hospitals.

It has an optical system that can rapidly gauge the optimal dose of methotrexate a patient needs, thereby reducing the risk of adverse effects.

“While effective, methotrexate is also highly toxic and can damage the healthy cells of patients, hence the importance of closely monitoring the drug’s concentration in the serum of treated individuals to adjust the dosage,” said study author Jean François Masson, PhD, of the University of Montreal in Quebec, Canada.

“The operation of the current [methotrexate monitoring] device is based on a cumbersome, expensive platform that requires experienced personnel because of the many samples that need to be manipulated.”

With this in mind, Dr Masson and his colleagues set out to simplify methotrexate monitoring.

In the course of their research, the team developed and manufactured a miniaturized device that works by surface plasmon resonance. It measures the concentration of serum methotrexate through gold nanoparticles on the surface of a receptacle.

In “competing” with methotrexate to block the enzyme dihydrofolate reductase, the gold nanoparticles change the color of the light detected by the instrument. And the color of the light detected reflects the exact concentration of the drug in the blood sample.

The researchers compared the accuracy of measurements taken with the new device to those taken with equipment used at the Maisonneuve-Rosemont Hospital in Montreal.

“Testing was conclusive,” Dr Masson said. “Not only were the measurements as accurate, but our device took less than 60 seconds to produce results, compared to 30 minutes for current devices.”

Moreover, the comparative tests were performed by lab technicians who were not experienced with surface plasmon resonance and did not encounter major difficulties in operating the new equipment or obtaining the same conclusive results as Dr Masson and his research team.

“In the near future, we can foresee the device in doctors’ offices or even at the bedside, where patients would receive individualized and optimal doses while minimizing the risk of complications,” Dr Masson said.

“While traditional equipment requires an investment of around $100,000, the new mobile device would likely cost 10 times less, around $10,000.”

Red blood cells

The US Food and Drug Administration (FDA) has granted the complement inhibitor AMY-101 orphan status as a treatment for paroxysmal nocturnal

hemoglobinuria (PNH).

Roughly 2 months ago, the European Medicines Agency (EMA) did the same.

Orphan designation will allow Amyndas Pharmaceuticals, the company developing AMY-101, to proceed with expedited clinical development. The company is

planning to move the drug into clinical trials in 2015.

If AMY-101 is approved by the FDA, orphan status will allow for a 7-year period of market exclusivity from product launch in the US. It will also allow Amyndas to apply for research funding, tax credits for certain research expenses, and assistance for clinical research study design. It provides a waiver from the FDA’s Prescription Drug User Fee as well.

“Receiving the orphan drug designation from both the FDA and the EMA is an important achievement and a key milestone in the development pathway of AMY-101, and we are optimistic regarding the long-term potential of this potent complement inhibitor,” said John Lambris, PhD, of the University of Pennsylvania.

Dr Lambris developed AMY-101 at the University of Pennsylvania, and the university licensed the drug to Amyndas Pharmaceuticals. Dr Lambris is a founder and equity holder of Amyndas Pharmaceuticals.

About AMY-101 and PNH

PNH is caused by the defective expression of regulatory proteins on the surface of blood cells, which leaves them vulnerable to complement attack. This can lead to hemolysis, which results in severe anemia and contributes to a high risk of thrombosis.

The monoclonal antibody eculizumab is often successful in treating PNH, but roughly a third of patients do not respond well to the drug and still require blood transfusions to manage their anemia.

Research has suggested this lack of response is due to fragments of complement C3 proteins on the surface of the patients’ red blood cells, which are eventually attacked by immune cells.

In an attempt to overcome this problem, Dr Lambris and his colleagues developed AMY-101. The drug is designed to inhibit C3, thereby preventing hemolysis and immune cell recognition.

The researchers have investigated the effects of AMY-101 on self-attack and the resulting hemolysis in human PNH cells and found the drug to be active.

These results have not been published, but the group has published results with a C3 inhibitor known as Cp40, and AMY-101 is based on Cp40.

The researchers reported in Blood that Cp40 and its long-acting form, PEG-Cp40, effectively inhibited hemolysis and efficiently prevented the deposition of C3 fragments on red blood cells from patients with PNH.

Red blood cells

The US Food and Drug Administration (FDA) has granted the complement inhibitor AMY-101 orphan status as a treatment for paroxysmal nocturnal

hemoglobinuria (PNH).

Roughly 2 months ago, the European Medicines Agency (EMA) did the same.

Orphan designation will allow Amyndas Pharmaceuticals, the company developing AMY-101, to proceed with expedited clinical development. The company is

planning to move the drug into clinical trials in 2015.

If AMY-101 is approved by the FDA, orphan status will allow for a 7-year period of market exclusivity from product launch in the US. It will also allow Amyndas to apply for research funding, tax credits for certain research expenses, and assistance for clinical research study design. It provides a waiver from the FDA’s Prescription Drug User Fee as well.

“Receiving the orphan drug designation from both the FDA and the EMA is an important achievement and a key milestone in the development pathway of AMY-101, and we are optimistic regarding the long-term potential of this potent complement inhibitor,” said John Lambris, PhD, of the University of Pennsylvania.

Dr Lambris developed AMY-101 at the University of Pennsylvania, and the university licensed the drug to Amyndas Pharmaceuticals. Dr Lambris is a founder and equity holder of Amyndas Pharmaceuticals.

About AMY-101 and PNH

PNH is caused by the defective expression of regulatory proteins on the surface of blood cells, which leaves them vulnerable to complement attack. This can lead to hemolysis, which results in severe anemia and contributes to a high risk of thrombosis.

The monoclonal antibody eculizumab is often successful in treating PNH, but roughly a third of patients do not respond well to the drug and still require blood transfusions to manage their anemia.

Research has suggested this lack of response is due to fragments of complement C3 proteins on the surface of the patients’ red blood cells, which are eventually attacked by immune cells.

In an attempt to overcome this problem, Dr Lambris and his colleagues developed AMY-101. The drug is designed to inhibit C3, thereby preventing hemolysis and immune cell recognition.

The researchers have investigated the effects of AMY-101 on self-attack and the resulting hemolysis in human PNH cells and found the drug to be active.

These results have not been published, but the group has published results with a C3 inhibitor known as Cp40, and AMY-101 is based on Cp40.

The researchers reported in Blood that Cp40 and its long-acting form, PEG-Cp40, effectively inhibited hemolysis and efficiently prevented the deposition of C3 fragments on red blood cells from patients with PNH.

Red blood cells

The US Food and Drug Administration (FDA) has granted the complement inhibitor AMY-101 orphan status as a treatment for paroxysmal nocturnal

hemoglobinuria (PNH).

Roughly 2 months ago, the European Medicines Agency (EMA) did the same.

Orphan designation will allow Amyndas Pharmaceuticals, the company developing AMY-101, to proceed with expedited clinical development. The company is

planning to move the drug into clinical trials in 2015.

If AMY-101 is approved by the FDA, orphan status will allow for a 7-year period of market exclusivity from product launch in the US. It will also allow Amyndas to apply for research funding, tax credits for certain research expenses, and assistance for clinical research study design. It provides a waiver from the FDA’s Prescription Drug User Fee as well.

“Receiving the orphan drug designation from both the FDA and the EMA is an important achievement and a key milestone in the development pathway of AMY-101, and we are optimistic regarding the long-term potential of this potent complement inhibitor,” said John Lambris, PhD, of the University of Pennsylvania.

Dr Lambris developed AMY-101 at the University of Pennsylvania, and the university licensed the drug to Amyndas Pharmaceuticals. Dr Lambris is a founder and equity holder of Amyndas Pharmaceuticals.

About AMY-101 and PNH

PNH is caused by the defective expression of regulatory proteins on the surface of blood cells, which leaves them vulnerable to complement attack. This can lead to hemolysis, which results in severe anemia and contributes to a high risk of thrombosis.

The monoclonal antibody eculizumab is often successful in treating PNH, but roughly a third of patients do not respond well to the drug and still require blood transfusions to manage their anemia.

Research has suggested this lack of response is due to fragments of complement C3 proteins on the surface of the patients’ red blood cells, which are eventually attacked by immune cells.

In an attempt to overcome this problem, Dr Lambris and his colleagues developed AMY-101. The drug is designed to inhibit C3, thereby preventing hemolysis and immune cell recognition.

The researchers have investigated the effects of AMY-101 on self-attack and the resulting hemolysis in human PNH cells and found the drug to be active.

These results have not been published, but the group has published results with a C3 inhibitor known as Cp40, and AMY-101 is based on Cp40.

The researchers reported in Blood that Cp40 and its long-acting form, PEG-Cp40, effectively inhibited hemolysis and efficiently prevented the deposition of C3 fragments on red blood cells from patients with PNH.

Woman texting

Credit: Ed Yourdon

Text messages reminding patients to take malaria medication can improve treatment adherence, according to a study published in PLOS ONE.

“When patients don’t complete their full medication regimen, diseases can develop resistance to treatment,” said study author Julia Raifman, a PhD candidate at the Harvard School of Public Health in Boston.

“And with infectious diseases like malaria, drug-resistant diseases can spread to others. We’ve already begun to see resistance to artemisinin in Southeast Asia. It would be catastrophic if that became widespread and there was no effective treatment for the most deadly form of malaria.”

Working with researchers at the non-profit Innovations for Poverty Action in Ghana, Raifman and her colleagues drew on previous research using SMS reminders in situations where people fail to follow through on intentions, such as saving money, paying back loans, or completing college financial aid forms.

The researchers recruited 1140 people in Ghana who were taking artemisinin-based combination therapy to treat malaria.

Participants used their mobile phones to enroll in an automated system, and the system randomly assigned half of them to receive the text message reminders to take their medication.

Local researchers followed up with the participants several days later at their homes to see how many pills they had taken. Subjects who received the texts were significantly more likely to finish the full regimen.

The researchers also tested whether a short or longer, more informative message would be more effective. They were surprised to find the shorter messages had a significant impact, but the longer ones did not.

“SMS reminders are a ‘nudge,’ not a ‘shove,’” said Aaron Dibner-Dunlap, of Innovations for Poverty Action. “They can help people follow through on something they originally intended to do, but human nature is tricky, and the science is still young.”

“We’re optimistic because the technology has become so widespread and inexpensive to administer, that for programs like this one that work, there’s huge potential for helping people at very low cost.”

Woman texting

Credit: Ed Yourdon

Text messages reminding patients to take malaria medication can improve treatment adherence, according to a study published in PLOS ONE.

“When patients don’t complete their full medication regimen, diseases can develop resistance to treatment,” said study author Julia Raifman, a PhD candidate at the Harvard School of Public Health in Boston.

“And with infectious diseases like malaria, drug-resistant diseases can spread to others. We’ve already begun to see resistance to artemisinin in Southeast Asia. It would be catastrophic if that became widespread and there was no effective treatment for the most deadly form of malaria.”

Working with researchers at the non-profit Innovations for Poverty Action in Ghana, Raifman and her colleagues drew on previous research using SMS reminders in situations where people fail to follow through on intentions, such as saving money, paying back loans, or completing college financial aid forms.

The researchers recruited 1140 people in Ghana who were taking artemisinin-based combination therapy to treat malaria.

Participants used their mobile phones to enroll in an automated system, and the system randomly assigned half of them to receive the text message reminders to take their medication.

Local researchers followed up with the participants several days later at their homes to see how many pills they had taken. Subjects who received the texts were significantly more likely to finish the full regimen.

The researchers also tested whether a short or longer, more informative message would be more effective. They were surprised to find the shorter messages had a significant impact, but the longer ones did not.

“SMS reminders are a ‘nudge,’ not a ‘shove,’” said Aaron Dibner-Dunlap, of Innovations for Poverty Action. “They can help people follow through on something they originally intended to do, but human nature is tricky, and the science is still young.”

“We’re optimistic because the technology has become so widespread and inexpensive to administer, that for programs like this one that work, there’s huge potential for helping people at very low cost.”

Woman texting

Credit: Ed Yourdon

Text messages reminding patients to take malaria medication can improve treatment adherence, according to a study published in PLOS ONE.

“When patients don’t complete their full medication regimen, diseases can develop resistance to treatment,” said study author Julia Raifman, a PhD candidate at the Harvard School of Public Health in Boston.

“And with infectious diseases like malaria, drug-resistant diseases can spread to others. We’ve already begun to see resistance to artemisinin in Southeast Asia. It would be catastrophic if that became widespread and there was no effective treatment for the most deadly form of malaria.”

Working with researchers at the non-profit Innovations for Poverty Action in Ghana, Raifman and her colleagues drew on previous research using SMS reminders in situations where people fail to follow through on intentions, such as saving money, paying back loans, or completing college financial aid forms.

The researchers recruited 1140 people in Ghana who were taking artemisinin-based combination therapy to treat malaria.

Participants used their mobile phones to enroll in an automated system, and the system randomly assigned half of them to receive the text message reminders to take their medication.

Local researchers followed up with the participants several days later at their homes to see how many pills they had taken. Subjects who received the texts were significantly more likely to finish the full regimen.

The researchers also tested whether a short or longer, more informative message would be more effective. They were surprised to find the shorter messages had a significant impact, but the longer ones did not.

“SMS reminders are a ‘nudge,’ not a ‘shove,’” said Aaron Dibner-Dunlap, of Innovations for Poverty Action. “They can help people follow through on something they originally intended to do, but human nature is tricky, and the science is still young.”

“We’re optimistic because the technology has become so widespread and inexpensive to administer, that for programs like this one that work, there’s huge potential for helping people at very low cost.”

Heart surgery

Credit: University of Ottawa

Heart Institute

VANCOUVER—In a large study, heart surgery patients who received recently donated blood had significantly fewer post-operative complications than those who received blood stored for more than 2 weeks.

Patients who received newer blood had a lower rate of mortality, infection, and renal failure.

They were also less likely to require prolonged ventilation or re-exploration for bleeding.

Ansar Hassan, MD, PhD, of Saint John Regional Hospital in New Brunswick, Canada, and his colleagues presented these results at the Canadian Cardiovascular Congress as abstract 562.

The researchers examined records at the New Brunswick Heart Centre in Saint John for non-emergency heart surgeries performed from January 2005 to September 2013 on patients who received red blood cells during or after surgery and who stayed in the hospital less than 30 days.

Of 2015 patients, slightly more than half (n=1052) received only blood that was donated within 14 days of the transfusion. The rest of the patients received some or only blood that was donated more than 14 days before transfusion. Canadian protocols allow blood to be stored and used up to 6 weeks after donation.

Patients who received newer blood were more likely to be female, have unstable angina, to have undergone isolated coronary artery bypass graft or valve surgery, to have experienced shorter bypass and cross-clamp times, and to have left the operating room on inotropes.

After surgery, patients who received newer blood had a lower rate of mortality (1.7% vs 3.3%, P=0.02), infection (3.2% vs 5.4%, P=0.02), atrial fibrillation (43.8% vs 47.3%, P=0.12), and renal failure (12.8% vs 17.7%, P=0.0003).

In addition, they were less likely to require ventilation for more than 24 hours (3% vs 7.7%, P<0.0001) or re-exploration for bleeding (1.5% vs 3.1%, P=0.02).

After the researchers adjusted for differences in baseline and intra-operative characteristics, receiving newer blood was associated with a significant reduction in a composite of the aforementioned outcomes (odds ratio=0.79, P=0.01).

“The findings show that we need to pay attention to the age of the blood we give cardiac surgery patients,” Dr Hassan said. “Perhaps more importantly, we need new studies to determine what is driving this relationship between the age of blood and the outcomes we are seeing.”

Dr Hassan noted that previous studies have reached contradictory conclusions on this subject, which was a reason this study was conducted.

Heart surgery

Credit: University of Ottawa

Heart Institute

VANCOUVER—In a large study, heart surgery patients who received recently donated blood had significantly fewer post-operative complications than those who received blood stored for more than 2 weeks.

Patients who received newer blood had a lower rate of mortality, infection, and renal failure.

They were also less likely to require prolonged ventilation or re-exploration for bleeding.

Ansar Hassan, MD, PhD, of Saint John Regional Hospital in New Brunswick, Canada, and his colleagues presented these results at the Canadian Cardiovascular Congress as abstract 562.

The researchers examined records at the New Brunswick Heart Centre in Saint John for non-emergency heart surgeries performed from January 2005 to September 2013 on patients who received red blood cells during or after surgery and who stayed in the hospital less than 30 days.

Of 2015 patients, slightly more than half (n=1052) received only blood that was donated within 14 days of the transfusion. The rest of the patients received some or only blood that was donated more than 14 days before transfusion. Canadian protocols allow blood to be stored and used up to 6 weeks after donation.

Patients who received newer blood were more likely to be female, have unstable angina, to have undergone isolated coronary artery bypass graft or valve surgery, to have experienced shorter bypass and cross-clamp times, and to have left the operating room on inotropes.

After surgery, patients who received newer blood had a lower rate of mortality (1.7% vs 3.3%, P=0.02), infection (3.2% vs 5.4%, P=0.02), atrial fibrillation (43.8% vs 47.3%, P=0.12), and renal failure (12.8% vs 17.7%, P=0.0003).

In addition, they were less likely to require ventilation for more than 24 hours (3% vs 7.7%, P<0.0001) or re-exploration for bleeding (1.5% vs 3.1%, P=0.02).

After the researchers adjusted for differences in baseline and intra-operative characteristics, receiving newer blood was associated with a significant reduction in a composite of the aforementioned outcomes (odds ratio=0.79, P=0.01).

“The findings show that we need to pay attention to the age of the blood we give cardiac surgery patients,” Dr Hassan said. “Perhaps more importantly, we need new studies to determine what is driving this relationship between the age of blood and the outcomes we are seeing.”

Dr Hassan noted that previous studies have reached contradictory conclusions on this subject, which was a reason this study was conducted.

Heart surgery

Credit: University of Ottawa

Heart Institute

VANCOUVER—In a large study, heart surgery patients who received recently donated blood had significantly fewer post-operative complications than those who received blood stored for more than 2 weeks.

Patients who received newer blood had a lower rate of mortality, infection, and renal failure.

They were also less likely to require prolonged ventilation or re-exploration for bleeding.

Ansar Hassan, MD, PhD, of Saint John Regional Hospital in New Brunswick, Canada, and his colleagues presented these results at the Canadian Cardiovascular Congress as abstract 562.

The researchers examined records at the New Brunswick Heart Centre in Saint John for non-emergency heart surgeries performed from January 2005 to September 2013 on patients who received red blood cells during or after surgery and who stayed in the hospital less than 30 days.

Of 2015 patients, slightly more than half (n=1052) received only blood that was donated within 14 days of the transfusion. The rest of the patients received some or only blood that was donated more than 14 days before transfusion. Canadian protocols allow blood to be stored and used up to 6 weeks after donation.

Patients who received newer blood were more likely to be female, have unstable angina, to have undergone isolated coronary artery bypass graft or valve surgery, to have experienced shorter bypass and cross-clamp times, and to have left the operating room on inotropes.

After surgery, patients who received newer blood had a lower rate of mortality (1.7% vs 3.3%, P=0.02), infection (3.2% vs 5.4%, P=0.02), atrial fibrillation (43.8% vs 47.3%, P=0.12), and renal failure (12.8% vs 17.7%, P=0.0003).

In addition, they were less likely to require ventilation for more than 24 hours (3% vs 7.7%, P<0.0001) or re-exploration for bleeding (1.5% vs 3.1%, P=0.02).

After the researchers adjusted for differences in baseline and intra-operative characteristics, receiving newer blood was associated with a significant reduction in a composite of the aforementioned outcomes (odds ratio=0.79, P=0.01).

“The findings show that we need to pay attention to the age of the blood we give cardiac surgery patients,” Dr Hassan said. “Perhaps more importantly, we need new studies to determine what is driving this relationship between the age of blood and the outcomes we are seeing.”

Dr Hassan noted that previous studies have reached contradictory conclusions on this subject, which was a reason this study was conducted.

Woman on a scale

Obese youths with acute lymphoblastic leukemia (ALL) are known to have worse outcomes than their lean counterparts.

To gain more insight into this phenomenon, investigators set out to determine if body mass index (BMI) impacted ALL patients’ responses to initial chemotherapy.

The results showed that, following induction chemotherapy, obese patients were more than twice as likely to have minimal residual disease (MRD) than non-obese patients.

“Induction chemotherapy provides a patient’s best chance for remission or a cure,” said principal investigator Steven Mittelman, MD, PhD, of The Saban Research Institute of Children’s Hospital Los Angeles in California.

“Our findings indicate that a patient’s obesity negatively impacts the ability of chemotherapy to kill leukemia cells, reducing the odds of survival.”

The study, which was published in Blood, included 198 patients who were diagnosed with ALL and between the ages of 1 and 21 years.

Each patient’s BMI was converted to a percentile and classified according to the Center for Disease Control and Prevention’s thresholds for overweight (85% to 94%) and obese (greater than 95%). Patients with a BMI less than 85% were considered “lean.”

About one-third of the patients were obese or overweight at the time of diagnosis.

MRD was determined by testing bone marrow specimens at the end of induction therapy, and patients were followed for 2 to 5 years from the time of diagnosis.

The investigators found that lean patients with MRD had similar outcomes to obese patients without evidence of MRD. Obese patients with MRD had the worst outcomes.

Additionally, although nearly a quarter of the patients initially deemed “lean” gained weight and became obese during the first month of treatment, these patients still showed similar outcomes to those who remained lean.

“In addition to increasing a patient’s likelihood of having persistent disease following treatment, obesity appears to add a risk factor that changes the interaction between chemotherapy and residual leukemia cells,” said Hisham Abdel-Azim, MD, also of The Saban Research Institute.

Findings from this study offer new avenues for investigation that include modifying chemotherapy regimens for obese patients and working to change a patient’s weight status beginning at the time of diagnosis.

Woman on a scale

Obese youths with acute lymphoblastic leukemia (ALL) are known to have worse outcomes than their lean counterparts.

To gain more insight into this phenomenon, investigators set out to determine if body mass index (BMI) impacted ALL patients’ responses to initial chemotherapy.

The results showed that, following induction chemotherapy, obese patients were more than twice as likely to have minimal residual disease (MRD) than non-obese patients.

“Induction chemotherapy provides a patient’s best chance for remission or a cure,” said principal investigator Steven Mittelman, MD, PhD, of The Saban Research Institute of Children’s Hospital Los Angeles in California.

“Our findings indicate that a patient’s obesity negatively impacts the ability of chemotherapy to kill leukemia cells, reducing the odds of survival.”

The study, which was published in Blood, included 198 patients who were diagnosed with ALL and between the ages of 1 and 21 years.

Each patient’s BMI was converted to a percentile and classified according to the Center for Disease Control and Prevention’s thresholds for overweight (85% to 94%) and obese (greater than 95%). Patients with a BMI less than 85% were considered “lean.”

About one-third of the patients were obese or overweight at the time of diagnosis.

MRD was determined by testing bone marrow specimens at the end of induction therapy, and patients were followed for 2 to 5 years from the time of diagnosis.

The investigators found that lean patients with MRD had similar outcomes to obese patients without evidence of MRD. Obese patients with MRD had the worst outcomes.

Additionally, although nearly a quarter of the patients initially deemed “lean” gained weight and became obese during the first month of treatment, these patients still showed similar outcomes to those who remained lean.

“In addition to increasing a patient’s likelihood of having persistent disease following treatment, obesity appears to add a risk factor that changes the interaction between chemotherapy and residual leukemia cells,” said Hisham Abdel-Azim, MD, also of The Saban Research Institute.

Findings from this study offer new avenues for investigation that include modifying chemotherapy regimens for obese patients and working to change a patient’s weight status beginning at the time of diagnosis.

Woman on a scale

Obese youths with acute lymphoblastic leukemia (ALL) are known to have worse outcomes than their lean counterparts.

To gain more insight into this phenomenon, investigators set out to determine if body mass index (BMI) impacted ALL patients’ responses to initial chemotherapy.

The results showed that, following induction chemotherapy, obese patients were more than twice as likely to have minimal residual disease (MRD) than non-obese patients.

“Induction chemotherapy provides a patient’s best chance for remission or a cure,” said principal investigator Steven Mittelman, MD, PhD, of The Saban Research Institute of Children’s Hospital Los Angeles in California.

“Our findings indicate that a patient’s obesity negatively impacts the ability of chemotherapy to kill leukemia cells, reducing the odds of survival.”

The study, which was published in Blood, included 198 patients who were diagnosed with ALL and between the ages of 1 and 21 years.

Each patient’s BMI was converted to a percentile and classified according to the Center for Disease Control and Prevention’s thresholds for overweight (85% to 94%) and obese (greater than 95%). Patients with a BMI less than 85% were considered “lean.”

About one-third of the patients were obese or overweight at the time of diagnosis.

MRD was determined by testing bone marrow specimens at the end of induction therapy, and patients were followed for 2 to 5 years from the time of diagnosis.

The investigators found that lean patients with MRD had similar outcomes to obese patients without evidence of MRD. Obese patients with MRD had the worst outcomes.

Additionally, although nearly a quarter of the patients initially deemed “lean” gained weight and became obese during the first month of treatment, these patients still showed similar outcomes to those who remained lean.

“In addition to increasing a patient’s likelihood of having persistent disease following treatment, obesity appears to add a risk factor that changes the interaction between chemotherapy and residual leukemia cells,” said Hisham Abdel-Azim, MD, also of The Saban Research Institute.

Findings from this study offer new avenues for investigation that include modifying chemotherapy regimens for obese patients and working to change a patient’s weight status beginning at the time of diagnosis.