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Chemical could aid malaria control
Photo courtesy of the CDC
A chemical that disrupts hormone signaling in mosquitoes may reduce their ability to transmit malaria, according to a study published in PLOS Pathogens.
The findings suggest a potential new approach to combat spread of the disease.
“As insecticide resistance is spreading, new intervention methods to control mosquitoes are urgently needed,” said study author Flaminia Catteruccia, PhD, of the Harvard T. H. Chan School of Public Health in Boston, Massachusetts.
“Our study provides a new strategy based on the use of a non-toxic compound that prevents transmission of malaria parasites without killing the mosquito.”
Dr Catteruccia and her colleagues treated adult female Anopheles gambiae mosquitoes with a chemical known as dibenzoylhydrazine (DBH) to see how it would impact their biological processes.
DBH mimics the action of the steroid hormone 20-hydroxyecdysone, which plays a key role in the reproductive cycle of the female mosquito.
The researchers found various aspects of the mosquitoes’ life cycle to be disrupted after treatment with DBH.
DBH-treated mosquitoes produced and laid fewer eggs, didn’t mate successfully, and died more rapidly than non-treated mosquitoes. The effects were greater the higher the DBH dose.
And DBH-treated mosquitoes were less likely to be infected by malaria parasites.
To further explore the potential of hormone targeting as a malaria control tactic, the researchers fed their experimental results into a mathematical model of the mosquito life cycle.
The results suggest that applying DBH to bed nets or spraying it indoors could potentially reduce malaria transmission as effectively as insecticides.
The researchers noted that DBH compounds are not toxic to mammals, which would make them ideally suited for use in bed nets, where low toxicity is essential. 
Photo courtesy of the CDC
A chemical that disrupts hormone signaling in mosquitoes may reduce their ability to transmit malaria, according to a study published in PLOS Pathogens.
The findings suggest a potential new approach to combat spread of the disease.
“As insecticide resistance is spreading, new intervention methods to control mosquitoes are urgently needed,” said study author Flaminia Catteruccia, PhD, of the Harvard T. H. Chan School of Public Health in Boston, Massachusetts.
“Our study provides a new strategy based on the use of a non-toxic compound that prevents transmission of malaria parasites without killing the mosquito.”
Dr Catteruccia and her colleagues treated adult female Anopheles gambiae mosquitoes with a chemical known as dibenzoylhydrazine (DBH) to see how it would impact their biological processes.
DBH mimics the action of the steroid hormone 20-hydroxyecdysone, which plays a key role in the reproductive cycle of the female mosquito.
The researchers found various aspects of the mosquitoes’ life cycle to be disrupted after treatment with DBH.
DBH-treated mosquitoes produced and laid fewer eggs, didn’t mate successfully, and died more rapidly than non-treated mosquitoes. The effects were greater the higher the DBH dose.
And DBH-treated mosquitoes were less likely to be infected by malaria parasites.
To further explore the potential of hormone targeting as a malaria control tactic, the researchers fed their experimental results into a mathematical model of the mosquito life cycle.
The results suggest that applying DBH to bed nets or spraying it indoors could potentially reduce malaria transmission as effectively as insecticides.
The researchers noted that DBH compounds are not toxic to mammals, which would make them ideally suited for use in bed nets, where low toxicity is essential.
Photo courtesy of the CDC
A chemical that disrupts hormone signaling in mosquitoes may reduce their ability to transmit malaria, according to a study published in PLOS Pathogens.
The findings suggest a potential new approach to combat spread of the disease.
“As insecticide resistance is spreading, new intervention methods to control mosquitoes are urgently needed,” said study author Flaminia Catteruccia, PhD, of the Harvard T. H. Chan School of Public Health in Boston, Massachusetts.
“Our study provides a new strategy based on the use of a non-toxic compound that prevents transmission of malaria parasites without killing the mosquito.”
Dr Catteruccia and her colleagues treated adult female Anopheles gambiae mosquitoes with a chemical known as dibenzoylhydrazine (DBH) to see how it would impact their biological processes.
DBH mimics the action of the steroid hormone 20-hydroxyecdysone, which plays a key role in the reproductive cycle of the female mosquito.
The researchers found various aspects of the mosquitoes’ life cycle to be disrupted after treatment with DBH.
DBH-treated mosquitoes produced and laid fewer eggs, didn’t mate successfully, and died more rapidly than non-treated mosquitoes. The effects were greater the higher the DBH dose.
And DBH-treated mosquitoes were less likely to be infected by malaria parasites.
To further explore the potential of hormone targeting as a malaria control tactic, the researchers fed their experimental results into a mathematical model of the mosquito life cycle.
The results suggest that applying DBH to bed nets or spraying it indoors could potentially reduce malaria transmission as effectively as insecticides.
The researchers noted that DBH compounds are not toxic to mammals, which would make them ideally suited for use in bed nets, where low toxicity is essential.
Congenital CMV linked to increased risk of ALL
Photo by Vera Kratochvil
Newborns with congenital cytomegalovirus (CMV) infection may have an increased risk of developing acute lymphoblastic leukemia (ALL), according to a study published in Blood.
The data also suggest the risk may be particularly high among Hispanic children.
Researchers said this is the first study to suggest that congenital CMV infection is a risk factor for childhood ALL and is more prominent in Hispanic children.
To conduct this study, the researchers first identified all known infections present in the bone marrow of 127 children diagnosed with ALL and 38 children diagnosed with acute myeloid leukemia (AML).
The team found CMV infection was prevalent in children with ALL but rare in those with AML.
Next, the researchers looked for CMV in newborn blood samples from 268 children who went on to develop ALL. The team compared the samples with samples from 270 healthy children.
“Our goal in tracking CMV back from the time of diagnosis to the womb was to establish that this infection occurred well before initiation of disease,” said lead study author Stephen Francis, PhD, of the University of Nevada and University of California, San Francisco.
He and his colleagues found that children who went on to develop ALL were nearly 4 times more likely than control subjects to be CMV-positive at birth. The odds ratio was 3.71 (P=0.0016).
The odds ratio was 5.9 in Hispanic children and 2.1 in non-Hispanic whites. The researchers said this finding is particularly interesting because of the high rate of ALL observed in Hispanics.
“If it’s true that in utero CMV is one of the initiating events in the development of childhood leukemia, then control of the virus has the potential to be a prevention target,” Dr Francis said. “That’s the real take-home message.”
While this research is in the early stages, the researchers hope these results will inspire more studies that will validate these findings and lead to the development of a CMV vaccine.
“This is the first step, but if we do end up finding a causal link to the most common childhood cancer, we hope that will light a fire in terms of stopping mother-to-child transmission of CMV,” Dr Francis said.
Photo by Vera Kratochvil
Newborns with congenital cytomegalovirus (CMV) infection may have an increased risk of developing acute lymphoblastic leukemia (ALL), according to a study published in Blood.
The data also suggest the risk may be particularly high among Hispanic children.
Researchers said this is the first study to suggest that congenital CMV infection is a risk factor for childhood ALL and is more prominent in Hispanic children.
To conduct this study, the researchers first identified all known infections present in the bone marrow of 127 children diagnosed with ALL and 38 children diagnosed with acute myeloid leukemia (AML).
The team found CMV infection was prevalent in children with ALL but rare in those with AML.
Next, the researchers looked for CMV in newborn blood samples from 268 children who went on to develop ALL. The team compared the samples with samples from 270 healthy children.
“Our goal in tracking CMV back from the time of diagnosis to the womb was to establish that this infection occurred well before initiation of disease,” said lead study author Stephen Francis, PhD, of the University of Nevada and University of California, San Francisco.
He and his colleagues found that children who went on to develop ALL were nearly 4 times more likely than control subjects to be CMV-positive at birth. The odds ratio was 3.71 (P=0.0016).
The odds ratio was 5.9 in Hispanic children and 2.1 in non-Hispanic whites. The researchers said this finding is particularly interesting because of the high rate of ALL observed in Hispanics.
“If it’s true that in utero CMV is one of the initiating events in the development of childhood leukemia, then control of the virus has the potential to be a prevention target,” Dr Francis said. “That’s the real take-home message.”
While this research is in the early stages, the researchers hope these results will inspire more studies that will validate these findings and lead to the development of a CMV vaccine.
“This is the first step, but if we do end up finding a causal link to the most common childhood cancer, we hope that will light a fire in terms of stopping mother-to-child transmission of CMV,” Dr Francis said.
Photo by Vera Kratochvil
Newborns with congenital cytomegalovirus (CMV) infection may have an increased risk of developing acute lymphoblastic leukemia (ALL), according to a study published in Blood.
The data also suggest the risk may be particularly high among Hispanic children.
Researchers said this is the first study to suggest that congenital CMV infection is a risk factor for childhood ALL and is more prominent in Hispanic children.
To conduct this study, the researchers first identified all known infections present in the bone marrow of 127 children diagnosed with ALL and 38 children diagnosed with acute myeloid leukemia (AML).
The team found CMV infection was prevalent in children with ALL but rare in those with AML.
Next, the researchers looked for CMV in newborn blood samples from 268 children who went on to develop ALL. The team compared the samples with samples from 270 healthy children.
“Our goal in tracking CMV back from the time of diagnosis to the womb was to establish that this infection occurred well before initiation of disease,” said lead study author Stephen Francis, PhD, of the University of Nevada and University of California, San Francisco.
He and his colleagues found that children who went on to develop ALL were nearly 4 times more likely than control subjects to be CMV-positive at birth. The odds ratio was 3.71 (P=0.0016).
The odds ratio was 5.9 in Hispanic children and 2.1 in non-Hispanic whites. The researchers said this finding is particularly interesting because of the high rate of ALL observed in Hispanics.
“If it’s true that in utero CMV is one of the initiating events in the development of childhood leukemia, then control of the virus has the potential to be a prevention target,” Dr Francis said. “That’s the real take-home message.”
While this research is in the early stages, the researchers hope these results will inspire more studies that will validate these findings and lead to the development of a CMV vaccine.
“This is the first step, but if we do end up finding a causal link to the most common childhood cancer, we hope that will light a fire in terms of stopping mother-to-child transmission of CMV,” Dr Francis said.
Health Canada approves therapy for hemophilia A
Health Canada has approved the use of lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy, in hemophilia A patients of all ages.
Lonoctocog alfa is indicated for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes, for on-demand treatment to control bleeding episodes, and for perioperative management of bleeding (surgical prophylaxis).
Lonoctocog alfa is the first and only single-chain recombinant FVIII therapy for hemophilia A specifically designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.
The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.
Health Canada’s approval of lonoctocog alfa is based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).
Among patients who received lonoctocog alfa prophylactically, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12.
In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.
Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.
Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.
Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).
One patient withdrew from treatment due to hypersensitivity.
None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.
Results from the trial of adolescents/adults were published in Blood in August. Results from the trial of children were presented at the World Federation of Hemophilia 2016 World Congress in July.*
Health Canada has approved the use of lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy, in hemophilia A patients of all ages.
Lonoctocog alfa is indicated for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes, for on-demand treatment to control bleeding episodes, and for perioperative management of bleeding (surgical prophylaxis).
Lonoctocog alfa is the first and only single-chain recombinant FVIII therapy for hemophilia A specifically designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.
The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.
Health Canada’s approval of lonoctocog alfa is based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).
Among patients who received lonoctocog alfa prophylactically, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12.
In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.
Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.
Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.
Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).
One patient withdrew from treatment due to hypersensitivity.
None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.
Results from the trial of adolescents/adults were published in Blood in August. Results from the trial of children were presented at the World Federation of Hemophilia 2016 World Congress in July.*
Health Canada has approved the use of lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy, in hemophilia A patients of all ages.
Lonoctocog alfa is indicated for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes, for on-demand treatment to control bleeding episodes, and for perioperative management of bleeding (surgical prophylaxis).
Lonoctocog alfa is the first and only single-chain recombinant FVIII therapy for hemophilia A specifically designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.
The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.
Health Canada’s approval of lonoctocog alfa is based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).
Among patients who received lonoctocog alfa prophylactically, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12.
In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.
Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.
Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.
Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).
One patient withdrew from treatment due to hypersensitivity.
None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.
Results from the trial of adolescents/adults were published in Blood in August. Results from the trial of children were presented at the World Federation of Hemophilia 2016 World Congress in July.*
Characterizing FL transformation, progression
Patients with transformed follicular lymphoma (FL) and FL patients with early progression have “widely divergent patterns of clonal
dynamics,” according to researchers.
The team investigated the molecular events underlying transformation and early progression in FL and found that disparate evolutionary trajectories and mutational profiles drive these 2 distinct clinical endpoints.
Sohrab Shah, PhD, of the University of British Columbia in Vancouver, Canada, and his colleagues reported these findings in PLOS Medicine.
The researchers used whole-genome sequencing to analyze tumor specimens and matched normal specimens from 41 FL patients.
The team then classified the patients according to the following clinical endpoints:
- Patients who presented with transformation (n=15)
- Patients who experienced tumor progression within 2.5 years of starting treatment, without evidence of transformation (n=6)
- Patients who had neither transformation nor progression up to 5 years post-diagnosis (n=20).
The researchers also used targeted capture sequencing of known FL-associated genes in a larger cohort of 277 FL patients (395 samples) to investigate discrete genetic events that drive transformation and early progression.
Results showed that tumors that progress early evolve in different ways from those that transform.
The team found that, for tumors that transform, the cells or clones that constitute the majority of the aggressive tumor were extremely rare at diagnosis, if they were present at all.
In contrast, for early progressive FL, the clonal architecture remained similar from the time of diagnosis to relapse, indicating that the diagnostic tumor may already contain the properties that confer resistance to treatment.
Analysis of the larger cohort revealed genes and biological processes that were associated with transformation and progression.
The researchers identified 12 genes that were more commonly mutated at the time of transformation than the time of diagnosis—TP53, B2M, EZH2, MYC, CCND3, EBF1, PIM1, GNA13, ITPKB, CHD8, S1PR2, and P2RY8.
The team said their findings suggest that defective DNA damage response, increased proliferation, escape from immune surveillance, and loss of confinement within the germinal center are key features that drive histological transformation from indolent to aggressive lymphoma.
The researchers also identified 10 genes that were more commonly mutated in patients with early progression than in patients with late/no progression—B2M, BTG1, FAS, IKZF3, KMT2C, MKI67, MYD88, SOCS1, TP53, and XBP1.
The team noted that most patients with early progression (80%) had mutations in at least 1 of these 10 genes, but none of the genes were mutated at a frequency greater than 27%. This suggests that early progression is related to relatively infrequent genetic alterations.
The researchers said these findings provide a basis for future research on prognostic assay development and potential strategies for monitoring and treatment of patients with FL.
Patients with transformed follicular lymphoma (FL) and FL patients with early progression have “widely divergent patterns of clonal
dynamics,” according to researchers.
The team investigated the molecular events underlying transformation and early progression in FL and found that disparate evolutionary trajectories and mutational profiles drive these 2 distinct clinical endpoints.
Sohrab Shah, PhD, of the University of British Columbia in Vancouver, Canada, and his colleagues reported these findings in PLOS Medicine.
The researchers used whole-genome sequencing to analyze tumor specimens and matched normal specimens from 41 FL patients.
The team then classified the patients according to the following clinical endpoints:
- Patients who presented with transformation (n=15)
- Patients who experienced tumor progression within 2.5 years of starting treatment, without evidence of transformation (n=6)
- Patients who had neither transformation nor progression up to 5 years post-diagnosis (n=20).
The researchers also used targeted capture sequencing of known FL-associated genes in a larger cohort of 277 FL patients (395 samples) to investigate discrete genetic events that drive transformation and early progression.
Results showed that tumors that progress early evolve in different ways from those that transform.
The team found that, for tumors that transform, the cells or clones that constitute the majority of the aggressive tumor were extremely rare at diagnosis, if they were present at all.
In contrast, for early progressive FL, the clonal architecture remained similar from the time of diagnosis to relapse, indicating that the diagnostic tumor may already contain the properties that confer resistance to treatment.
Analysis of the larger cohort revealed genes and biological processes that were associated with transformation and progression.
The researchers identified 12 genes that were more commonly mutated at the time of transformation than the time of diagnosis—TP53, B2M, EZH2, MYC, CCND3, EBF1, PIM1, GNA13, ITPKB, CHD8, S1PR2, and P2RY8.
The team said their findings suggest that defective DNA damage response, increased proliferation, escape from immune surveillance, and loss of confinement within the germinal center are key features that drive histological transformation from indolent to aggressive lymphoma.
The researchers also identified 10 genes that were more commonly mutated in patients with early progression than in patients with late/no progression—B2M, BTG1, FAS, IKZF3, KMT2C, MKI67, MYD88, SOCS1, TP53, and XBP1.
The team noted that most patients with early progression (80%) had mutations in at least 1 of these 10 genes, but none of the genes were mutated at a frequency greater than 27%. This suggests that early progression is related to relatively infrequent genetic alterations.
The researchers said these findings provide a basis for future research on prognostic assay development and potential strategies for monitoring and treatment of patients with FL.
Patients with transformed follicular lymphoma (FL) and FL patients with early progression have “widely divergent patterns of clonal
dynamics,” according to researchers.
The team investigated the molecular events underlying transformation and early progression in FL and found that disparate evolutionary trajectories and mutational profiles drive these 2 distinct clinical endpoints.
Sohrab Shah, PhD, of the University of British Columbia in Vancouver, Canada, and his colleagues reported these findings in PLOS Medicine.
The researchers used whole-genome sequencing to analyze tumor specimens and matched normal specimens from 41 FL patients.
The team then classified the patients according to the following clinical endpoints:
- Patients who presented with transformation (n=15)
- Patients who experienced tumor progression within 2.5 years of starting treatment, without evidence of transformation (n=6)
- Patients who had neither transformation nor progression up to 5 years post-diagnosis (n=20).
The researchers also used targeted capture sequencing of known FL-associated genes in a larger cohort of 277 FL patients (395 samples) to investigate discrete genetic events that drive transformation and early progression.
Results showed that tumors that progress early evolve in different ways from those that transform.
The team found that, for tumors that transform, the cells or clones that constitute the majority of the aggressive tumor were extremely rare at diagnosis, if they were present at all.
In contrast, for early progressive FL, the clonal architecture remained similar from the time of diagnosis to relapse, indicating that the diagnostic tumor may already contain the properties that confer resistance to treatment.
Analysis of the larger cohort revealed genes and biological processes that were associated with transformation and progression.
The researchers identified 12 genes that were more commonly mutated at the time of transformation than the time of diagnosis—TP53, B2M, EZH2, MYC, CCND3, EBF1, PIM1, GNA13, ITPKB, CHD8, S1PR2, and P2RY8.
The team said their findings suggest that defective DNA damage response, increased proliferation, escape from immune surveillance, and loss of confinement within the germinal center are key features that drive histological transformation from indolent to aggressive lymphoma.
The researchers also identified 10 genes that were more commonly mutated in patients with early progression than in patients with late/no progression—B2M, BTG1, FAS, IKZF3, KMT2C, MKI67, MYD88, SOCS1, TP53, and XBP1.
The team noted that most patients with early progression (80%) had mutations in at least 1 of these 10 genes, but none of the genes were mutated at a frequency greater than 27%. This suggests that early progression is related to relatively infrequent genetic alterations.
The researchers said these findings provide a basis for future research on prognostic assay development and potential strategies for monitoring and treatment of patients with FL.
Platform could optimize treatment of ALL, other diseases
A digital health technology platform may prove useful for optimizing treatment of acute lymphoblastic leukemia (ALL), according to research published in SLAS Technology.
The platform is based on phenotypic personalized medicine (PPM), in which a patient’s response to treatment can be visually represented in the shape of a parabola.
The graph plots the drug dose along the horizontal axis and the patient’s response on the vertical axis.
Researchers said PPM has the ability to accurately identify a person’s optimal drug and dose combinations throughout an entire course of treatment.
“Phenotypic personalized medicine is like turbocharged artificial intelligence,” said study author Dean Ho, PhD, of the University of California, Los Angeles.
“It personalizes combination therapy to optimize efficacy and safety. The ability for our technology to continuously pinpoint the proper dosages of multiple drugs from such a large pool of possible combinations overcomes a challenge that is substantially more difficult than finding a needle in a haystack.”
In this study, Dr Ho and his colleagues used PPM to (retrospectively) individualize drug ratios/dosages in 2 pediatric patients with standard-risk ALL.
The researchers looked at the patients’ records to examine the administration of 4-drug maintenance regimens (dexamethasone, vincristine, mercaptopurine, and methotrexate).
The team said the drug doses served as the inputs, and maintaining absolute neutrophil counts and platelet counts within target ranges served as the outputs for optimization.
Using PPM, the researchers generated individualized 3-dimensional maps to determine the optimal drug ratios.
The team found their technology-suggested drug dosages were as much as 40% lower than clinical chemotherapy dosages, but they still maintained target neutrophil/platelet levels.
The parabolas showed that markedly different dosages of each drug were required to maintain normal cell counts for each patient.
The researchers said their results demonstrate a clear need to personalize ALL treatment and will serve as a foundation for a pending clinical trial to optimize multidrug chemotherapy.
“PPM has the ability to personalize combination therapy for a wide spectrum of diseases, making it a broadly applicable technology,” said study author Chih-Ming Ho, PhD, of the University of California, Los Angeles.
“The fact that we don’t need any information pertaining to a disease’s biological process in order to optimize and personalize treatment is a revolutionary advance. We’re at the interface of digital health and cancer treatment.”
The research team is planning to recruit patients for a prospective trial within the next year. The technology is approved for additional infectious disease and oncology studies.
A digital health technology platform may prove useful for optimizing treatment of acute lymphoblastic leukemia (ALL), according to research published in SLAS Technology.
The platform is based on phenotypic personalized medicine (PPM), in which a patient’s response to treatment can be visually represented in the shape of a parabola.
The graph plots the drug dose along the horizontal axis and the patient’s response on the vertical axis.
Researchers said PPM has the ability to accurately identify a person’s optimal drug and dose combinations throughout an entire course of treatment.
“Phenotypic personalized medicine is like turbocharged artificial intelligence,” said study author Dean Ho, PhD, of the University of California, Los Angeles.
“It personalizes combination therapy to optimize efficacy and safety. The ability for our technology to continuously pinpoint the proper dosages of multiple drugs from such a large pool of possible combinations overcomes a challenge that is substantially more difficult than finding a needle in a haystack.”
In this study, Dr Ho and his colleagues used PPM to (retrospectively) individualize drug ratios/dosages in 2 pediatric patients with standard-risk ALL.
The researchers looked at the patients’ records to examine the administration of 4-drug maintenance regimens (dexamethasone, vincristine, mercaptopurine, and methotrexate).
The team said the drug doses served as the inputs, and maintaining absolute neutrophil counts and platelet counts within target ranges served as the outputs for optimization.
Using PPM, the researchers generated individualized 3-dimensional maps to determine the optimal drug ratios.
The team found their technology-suggested drug dosages were as much as 40% lower than clinical chemotherapy dosages, but they still maintained target neutrophil/platelet levels.
The parabolas showed that markedly different dosages of each drug were required to maintain normal cell counts for each patient.
The researchers said their results demonstrate a clear need to personalize ALL treatment and will serve as a foundation for a pending clinical trial to optimize multidrug chemotherapy.
“PPM has the ability to personalize combination therapy for a wide spectrum of diseases, making it a broadly applicable technology,” said study author Chih-Ming Ho, PhD, of the University of California, Los Angeles.
“The fact that we don’t need any information pertaining to a disease’s biological process in order to optimize and personalize treatment is a revolutionary advance. We’re at the interface of digital health and cancer treatment.”
The research team is planning to recruit patients for a prospective trial within the next year. The technology is approved for additional infectious disease and oncology studies.
A digital health technology platform may prove useful for optimizing treatment of acute lymphoblastic leukemia (ALL), according to research published in SLAS Technology.
The platform is based on phenotypic personalized medicine (PPM), in which a patient’s response to treatment can be visually represented in the shape of a parabola.
The graph plots the drug dose along the horizontal axis and the patient’s response on the vertical axis.
Researchers said PPM has the ability to accurately identify a person’s optimal drug and dose combinations throughout an entire course of treatment.
“Phenotypic personalized medicine is like turbocharged artificial intelligence,” said study author Dean Ho, PhD, of the University of California, Los Angeles.
“It personalizes combination therapy to optimize efficacy and safety. The ability for our technology to continuously pinpoint the proper dosages of multiple drugs from such a large pool of possible combinations overcomes a challenge that is substantially more difficult than finding a needle in a haystack.”
In this study, Dr Ho and his colleagues used PPM to (retrospectively) individualize drug ratios/dosages in 2 pediatric patients with standard-risk ALL.
The researchers looked at the patients’ records to examine the administration of 4-drug maintenance regimens (dexamethasone, vincristine, mercaptopurine, and methotrexate).
The team said the drug doses served as the inputs, and maintaining absolute neutrophil counts and platelet counts within target ranges served as the outputs for optimization.
Using PPM, the researchers generated individualized 3-dimensional maps to determine the optimal drug ratios.
The team found their technology-suggested drug dosages were as much as 40% lower than clinical chemotherapy dosages, but they still maintained target neutrophil/platelet levels.
The parabolas showed that markedly different dosages of each drug were required to maintain normal cell counts for each patient.
The researchers said their results demonstrate a clear need to personalize ALL treatment and will serve as a foundation for a pending clinical trial to optimize multidrug chemotherapy.
“PPM has the ability to personalize combination therapy for a wide spectrum of diseases, making it a broadly applicable technology,” said study author Chih-Ming Ho, PhD, of the University of California, Los Angeles.
“The fact that we don’t need any information pertaining to a disease’s biological process in order to optimize and personalize treatment is a revolutionary advance. We’re at the interface of digital health and cancer treatment.”
The research team is planning to recruit patients for a prospective trial within the next year. The technology is approved for additional infectious disease and oncology studies.
Two mutations may help drive CBF-AML
2016 ASH Annual Meeting
SAN DIEGO—Researchers have found evidence to suggest that mutations in the CCND1 and CCND2 genes may contribute to the development of core-binding factor acute myeloid leukemia (CBF-AML).
The team noted that CBF-AML is defined by the presence of either t(8;21)(q22;q22)/RUNX1-RUNX1T1 or inv(16)(p13.1q22)/t(16;16)(p13.1;q22)/CBFB-MYH11.
However, the fusion genes alone are not capable of causing CBF-AML.
“The hematology community has long sought to determine what other factors in addition to the fusion genes occur in this special type of leukemia,” said Ann-Kathrin Eisfeld, MD, of The Ohio State University Comprehensive Cancer Center in Columbus.
“We are now the first to describe that mutations in CCND1—and among the first to describe that mutations in the sister gene CCND2—are unique features of CBF-AML with t(8;21). In addition, we have collected the first evidence that mutations in CCND2 lead to more aggressive growth of leukemia cell lines.”
Dr Eisfeld and her colleagues reported these findings in a paper published in Leukemia and in a poster presented at the 2016 ASH Annual Meeting (abstract 2740).
A previous study of genetic mutations in CBF-AML revealed the presence of at least 1 mutation in 85% of patients studied. This meant the remaining 15% of patients harbored other, undiscovered mutations.
For the current study, Dr Eisfeld and her colleagues searched CBF-AML samples for the missing mutations that, together with the fusion genes, might contribute to the leukemia in this subgroup of cases.
The team analyzed pretreatment bone marrow and peripheral blood samples from 177 adult CBF-AML patients who received similar treatment through a clinical trial conducted at multiple centers across the US.
Using a targeted, next-generation sequencing approach, the researchers looked for mutations in 84 leukemia- and/or cancer-associated genes. They also performed tests on blood or bone marrow cells to look for chromosomal irregularities.
The team discovered 2 significant mutations in the CCND1 and CCND2 genes, representing the first dual evidence of these recurrent mutations in patients with t(8;21)-positive CBF-AML.
CCND1 and CCND2 mutations were found in 15% (n=10) of patients with t(8;21)-positive CBF-AML. Two patients had mutations in CCND1, and 8 had mutations in CCND2.
The researchers also found a single CCND2 mutation in 1 (0.9%) patient with inv(16)-positive CBF-AML.
In comparison, the incidence of CCND1 and CCND2 mutations was 0.77% (n=11) in a cohort of 1426 patients with non-CBF-AML.
“This is extremely valuable information that was previously unknown,” Dr Eisfeld said, “and it might help us develop targeted therapies more likely to help patients with [CBF-AML] in the near future.”
2016 ASH Annual Meeting
SAN DIEGO—Researchers have found evidence to suggest that mutations in the CCND1 and CCND2 genes may contribute to the development of core-binding factor acute myeloid leukemia (CBF-AML).
The team noted that CBF-AML is defined by the presence of either t(8;21)(q22;q22)/RUNX1-RUNX1T1 or inv(16)(p13.1q22)/t(16;16)(p13.1;q22)/CBFB-MYH11.
However, the fusion genes alone are not capable of causing CBF-AML.
“The hematology community has long sought to determine what other factors in addition to the fusion genes occur in this special type of leukemia,” said Ann-Kathrin Eisfeld, MD, of The Ohio State University Comprehensive Cancer Center in Columbus.
“We are now the first to describe that mutations in CCND1—and among the first to describe that mutations in the sister gene CCND2—are unique features of CBF-AML with t(8;21). In addition, we have collected the first evidence that mutations in CCND2 lead to more aggressive growth of leukemia cell lines.”
Dr Eisfeld and her colleagues reported these findings in a paper published in Leukemia and in a poster presented at the 2016 ASH Annual Meeting (abstract 2740).
A previous study of genetic mutations in CBF-AML revealed the presence of at least 1 mutation in 85% of patients studied. This meant the remaining 15% of patients harbored other, undiscovered mutations.
For the current study, Dr Eisfeld and her colleagues searched CBF-AML samples for the missing mutations that, together with the fusion genes, might contribute to the leukemia in this subgroup of cases.
The team analyzed pretreatment bone marrow and peripheral blood samples from 177 adult CBF-AML patients who received similar treatment through a clinical trial conducted at multiple centers across the US.
Using a targeted, next-generation sequencing approach, the researchers looked for mutations in 84 leukemia- and/or cancer-associated genes. They also performed tests on blood or bone marrow cells to look for chromosomal irregularities.
The team discovered 2 significant mutations in the CCND1 and CCND2 genes, representing the first dual evidence of these recurrent mutations in patients with t(8;21)-positive CBF-AML.
CCND1 and CCND2 mutations were found in 15% (n=10) of patients with t(8;21)-positive CBF-AML. Two patients had mutations in CCND1, and 8 had mutations in CCND2.
The researchers also found a single CCND2 mutation in 1 (0.9%) patient with inv(16)-positive CBF-AML.
In comparison, the incidence of CCND1 and CCND2 mutations was 0.77% (n=11) in a cohort of 1426 patients with non-CBF-AML.
“This is extremely valuable information that was previously unknown,” Dr Eisfeld said, “and it might help us develop targeted therapies more likely to help patients with [CBF-AML] in the near future.”
2016 ASH Annual Meeting
SAN DIEGO—Researchers have found evidence to suggest that mutations in the CCND1 and CCND2 genes may contribute to the development of core-binding factor acute myeloid leukemia (CBF-AML).
The team noted that CBF-AML is defined by the presence of either t(8;21)(q22;q22)/RUNX1-RUNX1T1 or inv(16)(p13.1q22)/t(16;16)(p13.1;q22)/CBFB-MYH11.
However, the fusion genes alone are not capable of causing CBF-AML.
“The hematology community has long sought to determine what other factors in addition to the fusion genes occur in this special type of leukemia,” said Ann-Kathrin Eisfeld, MD, of The Ohio State University Comprehensive Cancer Center in Columbus.
“We are now the first to describe that mutations in CCND1—and among the first to describe that mutations in the sister gene CCND2—are unique features of CBF-AML with t(8;21). In addition, we have collected the first evidence that mutations in CCND2 lead to more aggressive growth of leukemia cell lines.”
Dr Eisfeld and her colleagues reported these findings in a paper published in Leukemia and in a poster presented at the 2016 ASH Annual Meeting (abstract 2740).
A previous study of genetic mutations in CBF-AML revealed the presence of at least 1 mutation in 85% of patients studied. This meant the remaining 15% of patients harbored other, undiscovered mutations.
For the current study, Dr Eisfeld and her colleagues searched CBF-AML samples for the missing mutations that, together with the fusion genes, might contribute to the leukemia in this subgroup of cases.
The team analyzed pretreatment bone marrow and peripheral blood samples from 177 adult CBF-AML patients who received similar treatment through a clinical trial conducted at multiple centers across the US.
Using a targeted, next-generation sequencing approach, the researchers looked for mutations in 84 leukemia- and/or cancer-associated genes. They also performed tests on blood or bone marrow cells to look for chromosomal irregularities.
The team discovered 2 significant mutations in the CCND1 and CCND2 genes, representing the first dual evidence of these recurrent mutations in patients with t(8;21)-positive CBF-AML.
CCND1 and CCND2 mutations were found in 15% (n=10) of patients with t(8;21)-positive CBF-AML. Two patients had mutations in CCND1, and 8 had mutations in CCND2.
The researchers also found a single CCND2 mutation in 1 (0.9%) patient with inv(16)-positive CBF-AML.
In comparison, the incidence of CCND1 and CCND2 mutations was 0.77% (n=11) in a cohort of 1426 patients with non-CBF-AML.
“This is extremely valuable information that was previously unknown,” Dr Eisfeld said, “and it might help us develop targeted therapies more likely to help patients with [CBF-AML] in the near future.”
EC authorizes new use for ofatumumab in CLL
Photo courtesy of GSK
The European Commission (EC) has granted marketing authorization for ofatumumab (Arzerra®) to be used in combination with fludarabine and cyclophosphamide (FC) in the treatment of adults with relapsed chronic lymphocytic leukemia (CLL).
Ofatumumab is a monoclonal antibody designed to target CD20. The drug is marketed under a collaboration agreement between Genmab and Novartis.
The EC previously authorized the use of ofatumumab as a single agent to treat CLL patients who are refractory to fludarabine and alemtuzumab.
The agency also authorized the use of ofatumumab in combination with chlorambucil or bendamustine in CLL patients who have not received prior therapy and are not eligible for fludarabine-based therapy.
The EC’s decision to approve the use of ofatumumab in combination with FC was based on results from the phase 3 COMPLEMENT 2 study, which were published in Leukemia & Lymphoma in October.
The trial enrolled 365 patients with relapsed CLL. The patients were randomized 1:1 to receive up to 6 cycles of ofatumumab in combination with FC or up to 6 cycles of FC alone.
The primary endpoint was progression-free survival, as assessed by an independent review committee.
The median progression-free survival was 28.9 months for patients receiving ofatumumab plus FC, compared to 18.8 months for patients receiving FC only (hazard ratio=0.67, P=0.0032).
The incidence of grade 3 or higher adverse events was 74% in the ofatumumab-plus-FC arm and 69% in the FC-only arm. Neutropenia was the most common of these events, occurring in 49% and 36% of patients, respectively.
Photo courtesy of GSK
The European Commission (EC) has granted marketing authorization for ofatumumab (Arzerra®) to be used in combination with fludarabine and cyclophosphamide (FC) in the treatment of adults with relapsed chronic lymphocytic leukemia (CLL).
Ofatumumab is a monoclonal antibody designed to target CD20. The drug is marketed under a collaboration agreement between Genmab and Novartis.
The EC previously authorized the use of ofatumumab as a single agent to treat CLL patients who are refractory to fludarabine and alemtuzumab.
The agency also authorized the use of ofatumumab in combination with chlorambucil or bendamustine in CLL patients who have not received prior therapy and are not eligible for fludarabine-based therapy.
The EC’s decision to approve the use of ofatumumab in combination with FC was based on results from the phase 3 COMPLEMENT 2 study, which were published in Leukemia & Lymphoma in October.
The trial enrolled 365 patients with relapsed CLL. The patients were randomized 1:1 to receive up to 6 cycles of ofatumumab in combination with FC or up to 6 cycles of FC alone.
The primary endpoint was progression-free survival, as assessed by an independent review committee.
The median progression-free survival was 28.9 months for patients receiving ofatumumab plus FC, compared to 18.8 months for patients receiving FC only (hazard ratio=0.67, P=0.0032).
The incidence of grade 3 or higher adverse events was 74% in the ofatumumab-plus-FC arm and 69% in the FC-only arm. Neutropenia was the most common of these events, occurring in 49% and 36% of patients, respectively.
Photo courtesy of GSK
The European Commission (EC) has granted marketing authorization for ofatumumab (Arzerra®) to be used in combination with fludarabine and cyclophosphamide (FC) in the treatment of adults with relapsed chronic lymphocytic leukemia (CLL).
Ofatumumab is a monoclonal antibody designed to target CD20. The drug is marketed under a collaboration agreement between Genmab and Novartis.
The EC previously authorized the use of ofatumumab as a single agent to treat CLL patients who are refractory to fludarabine and alemtuzumab.
The agency also authorized the use of ofatumumab in combination with chlorambucil or bendamustine in CLL patients who have not received prior therapy and are not eligible for fludarabine-based therapy.
The EC’s decision to approve the use of ofatumumab in combination with FC was based on results from the phase 3 COMPLEMENT 2 study, which were published in Leukemia & Lymphoma in October.
The trial enrolled 365 patients with relapsed CLL. The patients were randomized 1:1 to receive up to 6 cycles of ofatumumab in combination with FC or up to 6 cycles of FC alone.
The primary endpoint was progression-free survival, as assessed by an independent review committee.
The median progression-free survival was 28.9 months for patients receiving ofatumumab plus FC, compared to 18.8 months for patients receiving FC only (hazard ratio=0.67, P=0.0032).
The incidence of grade 3 or higher adverse events was 74% in the ofatumumab-plus-FC arm and 69% in the FC-only arm. Neutropenia was the most common of these events, occurring in 49% and 36% of patients, respectively.
Predicting therapy-related myeloid neoplasms
Photo courtesy of
MD Anderson Cancer Center
SAN DIEGO―Clonal hematopoiesis could be used as a predictive marker to identify cancer patients at risk of developing therapy-related myeloid neoplasms (t-MNs), according to researchers.
The team conducted a case-control study, which showed that patients who developed t-MNs—acute myeloid leukemia and myelodysplastic syndromes—were significantly more likely than patients without t-MNs to have clonal hematopoiesis at the time of primary cancer diagnosis.
“Based on these findings, we believe pre-leukemic mutations may function as a new biomarker that would predict t-MN development,” said Andy Futreal, PhD, of The University of Texas MD Anderson Cancer Center in Houston.
Dr Futreal and his colleagues reported these findings in The Lancet Oncology.
Co-author Koichi Takashi, MD, also of MD Anderson, presented the findings at the 2016 ASH Annual Meeting (abstract 38).
Initial cohort
The researchers analyzed data on patients treated at MD Anderson from 1997 to 2015.
The 14 cases the team identified had been treated for a primary cancer and later developed t-MNs. The 54 age-matched control subjects had been treated for lymphoma, received combination chemotherapy, and did not develop t-MNs after at least 5 years of follow-up.
For both cases and controls, the researchers performed gene sequencing on pre-treatment peripheral blood samples. For cases, the researchers also performed targeted gene sequencing on bone marrow samples taken at t-MN diagnosis.
“We found that prevalence of pre-leukemic mutations was significantly higher in patients who developed t-MNs versus those who did not,” Dr Futreal said.
Clonal hematopoiesis was present in 71% of cases (n=10) and 31% of controls (n=17).
“We found genetic mutations that are present in t-MNs leukemia samples actually could be found in blood samples obtained at the time of their original cancer diagnosis,” Dr Takashi noted.
Overall, the cumulative incidence of t-MNs at 5 years was significantly higher in patients with clonal hematopoiesis than in those without it—30% and 7%, respectively (P=0.016).
Validation cohort
The researchers also assessed clonal hematopoiesis in an external cohort of 74 patients with lymphoma who were treated in a trial of front-line chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone, with or without melatonin.
In this cohort, 7% (n=5) of patients developed t-MNs. Eighty percent of these patients (n=4) had clonal hematopoiesis.
Of the 69 patients who did not develop t-MNs, 16% (n=11) had clonal hematopoiesis.
The cumulative incidence of t-MNs at 10 years was significantly higher in patients with clonal hematopoiesis than in those without it—29% and 0%, respectively (P=0.0009).
Multivariate analysis suggested clonal hematopoiesis significantly increased the risk of t-MNs, with a hazard ratio of 13.7 (P=0.013).
“[W]e believe the data suggest potential approaches of screening for clonal hematopoiesis in cancer patients that may identify patients at risk of developing t-MNs, although further studies are needed,” Dr Takashi concluded.
Photo courtesy of
MD Anderson Cancer Center
SAN DIEGO―Clonal hematopoiesis could be used as a predictive marker to identify cancer patients at risk of developing therapy-related myeloid neoplasms (t-MNs), according to researchers.
The team conducted a case-control study, which showed that patients who developed t-MNs—acute myeloid leukemia and myelodysplastic syndromes—were significantly more likely than patients without t-MNs to have clonal hematopoiesis at the time of primary cancer diagnosis.
“Based on these findings, we believe pre-leukemic mutations may function as a new biomarker that would predict t-MN development,” said Andy Futreal, PhD, of The University of Texas MD Anderson Cancer Center in Houston.
Dr Futreal and his colleagues reported these findings in The Lancet Oncology.
Co-author Koichi Takashi, MD, also of MD Anderson, presented the findings at the 2016 ASH Annual Meeting (abstract 38).
Initial cohort
The researchers analyzed data on patients treated at MD Anderson from 1997 to 2015.
The 14 cases the team identified had been treated for a primary cancer and later developed t-MNs. The 54 age-matched control subjects had been treated for lymphoma, received combination chemotherapy, and did not develop t-MNs after at least 5 years of follow-up.
For both cases and controls, the researchers performed gene sequencing on pre-treatment peripheral blood samples. For cases, the researchers also performed targeted gene sequencing on bone marrow samples taken at t-MN diagnosis.
“We found that prevalence of pre-leukemic mutations was significantly higher in patients who developed t-MNs versus those who did not,” Dr Futreal said.
Clonal hematopoiesis was present in 71% of cases (n=10) and 31% of controls (n=17).
“We found genetic mutations that are present in t-MNs leukemia samples actually could be found in blood samples obtained at the time of their original cancer diagnosis,” Dr Takashi noted.
Overall, the cumulative incidence of t-MNs at 5 years was significantly higher in patients with clonal hematopoiesis than in those without it—30% and 7%, respectively (P=0.016).
Validation cohort
The researchers also assessed clonal hematopoiesis in an external cohort of 74 patients with lymphoma who were treated in a trial of front-line chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone, with or without melatonin.
In this cohort, 7% (n=5) of patients developed t-MNs. Eighty percent of these patients (n=4) had clonal hematopoiesis.
Of the 69 patients who did not develop t-MNs, 16% (n=11) had clonal hematopoiesis.
The cumulative incidence of t-MNs at 10 years was significantly higher in patients with clonal hematopoiesis than in those without it—29% and 0%, respectively (P=0.0009).
Multivariate analysis suggested clonal hematopoiesis significantly increased the risk of t-MNs, with a hazard ratio of 13.7 (P=0.013).
“[W]e believe the data suggest potential approaches of screening for clonal hematopoiesis in cancer patients that may identify patients at risk of developing t-MNs, although further studies are needed,” Dr Takashi concluded.
Photo courtesy of
MD Anderson Cancer Center
SAN DIEGO―Clonal hematopoiesis could be used as a predictive marker to identify cancer patients at risk of developing therapy-related myeloid neoplasms (t-MNs), according to researchers.
The team conducted a case-control study, which showed that patients who developed t-MNs—acute myeloid leukemia and myelodysplastic syndromes—were significantly more likely than patients without t-MNs to have clonal hematopoiesis at the time of primary cancer diagnosis.
“Based on these findings, we believe pre-leukemic mutations may function as a new biomarker that would predict t-MN development,” said Andy Futreal, PhD, of The University of Texas MD Anderson Cancer Center in Houston.
Dr Futreal and his colleagues reported these findings in The Lancet Oncology.
Co-author Koichi Takashi, MD, also of MD Anderson, presented the findings at the 2016 ASH Annual Meeting (abstract 38).
Initial cohort
The researchers analyzed data on patients treated at MD Anderson from 1997 to 2015.
The 14 cases the team identified had been treated for a primary cancer and later developed t-MNs. The 54 age-matched control subjects had been treated for lymphoma, received combination chemotherapy, and did not develop t-MNs after at least 5 years of follow-up.
For both cases and controls, the researchers performed gene sequencing on pre-treatment peripheral blood samples. For cases, the researchers also performed targeted gene sequencing on bone marrow samples taken at t-MN diagnosis.
“We found that prevalence of pre-leukemic mutations was significantly higher in patients who developed t-MNs versus those who did not,” Dr Futreal said.
Clonal hematopoiesis was present in 71% of cases (n=10) and 31% of controls (n=17).
“We found genetic mutations that are present in t-MNs leukemia samples actually could be found in blood samples obtained at the time of their original cancer diagnosis,” Dr Takashi noted.
Overall, the cumulative incidence of t-MNs at 5 years was significantly higher in patients with clonal hematopoiesis than in those without it—30% and 7%, respectively (P=0.016).
Validation cohort
The researchers also assessed clonal hematopoiesis in an external cohort of 74 patients with lymphoma who were treated in a trial of front-line chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone, with or without melatonin.
In this cohort, 7% (n=5) of patients developed t-MNs. Eighty percent of these patients (n=4) had clonal hematopoiesis.
Of the 69 patients who did not develop t-MNs, 16% (n=11) had clonal hematopoiesis.
The cumulative incidence of t-MNs at 10 years was significantly higher in patients with clonal hematopoiesis than in those without it—29% and 0%, respectively (P=0.0009).
Multivariate analysis suggested clonal hematopoiesis significantly increased the risk of t-MNs, with a hazard ratio of 13.7 (P=0.013).
“[W]e believe the data suggest potential approaches of screening for clonal hematopoiesis in cancer patients that may identify patients at risk of developing t-MNs, although further studies are needed,” Dr Takashi concluded.
Guidelines reduce blood draws in critically ill kids
for a child in the pediatric ICU
Photo courtesy of
Johns Hopkins Medicine
New research suggests clinical practice guidelines can reduce the number of potentially unnecessary blood culture draws in critically ill children without endangering doctors’ ability to diagnose and treat sepsis.
The guidelines consist of 2 documents—a screening checklist and a decision algorithm.
In a single-center study, clinicians consulted these documents when considering ordering blood cultures for patients in a pediatric intensive care unit (ICU).
The clinicians said there was an immediate reduction in unnecessary blood draws after they began using these guidelines, and they were able to sustain the reduction over time.
Aaron Milstone, MD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues described these results in JAMA Pediatrics.
The guidelines were created by a team of nurses, vascular access specialists, and physicians across specialties. The team created a fever/sepsis screening checklist and an accompanying decision-making flow chart designed to guide clinicians in the decision to draw blood.
These tools were posted in the pediatric ICU at The Johns Hopkins Hospital with instructions to be completed at the bedside by nurses and physicians. Each week, the team would meet to evaluate the data gathered, review how many cultures were sent from the unit, and discuss in detail individual cases where blood draws were necessary.
The researchers compared patient length of stay, mortality, readmission, and the number of episodes of suspected septic shock at the hospital before and after this intervention was implemented.
In the year before the team introduced the tools, there were 2204 patient visits to the pediatric ICU and 1807 blood cultures drawn.
After the intervention, there were 984 blood cultures drawn for 2356 patient visits, almost halving the number of blood cultures per patient day.
Comparing the pre- and post-intervention periods, there was no statistical difference in the occurrence of septic shock, hospital mortality, or hospital readmission.
Dr Milstone said this means patients experienced no increased risk of a missed sepsis diagnosis because of the intervention.
He and his colleagues said the future directions of this research include further exploring the implications this intervention may have for antibiotic use as well as working to implement the tools in other ICUs. The tools are already being tried at Johns Hopkins All Children’s Hospital in Florida and in the pediatric ICU at the University of Virginia.
for a child in the pediatric ICU
Photo courtesy of
Johns Hopkins Medicine
New research suggests clinical practice guidelines can reduce the number of potentially unnecessary blood culture draws in critically ill children without endangering doctors’ ability to diagnose and treat sepsis.
The guidelines consist of 2 documents—a screening checklist and a decision algorithm.
In a single-center study, clinicians consulted these documents when considering ordering blood cultures for patients in a pediatric intensive care unit (ICU).
The clinicians said there was an immediate reduction in unnecessary blood draws after they began using these guidelines, and they were able to sustain the reduction over time.
Aaron Milstone, MD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues described these results in JAMA Pediatrics.
The guidelines were created by a team of nurses, vascular access specialists, and physicians across specialties. The team created a fever/sepsis screening checklist and an accompanying decision-making flow chart designed to guide clinicians in the decision to draw blood.
These tools were posted in the pediatric ICU at The Johns Hopkins Hospital with instructions to be completed at the bedside by nurses and physicians. Each week, the team would meet to evaluate the data gathered, review how many cultures were sent from the unit, and discuss in detail individual cases where blood draws were necessary.
The researchers compared patient length of stay, mortality, readmission, and the number of episodes of suspected septic shock at the hospital before and after this intervention was implemented.
In the year before the team introduced the tools, there were 2204 patient visits to the pediatric ICU and 1807 blood cultures drawn.
After the intervention, there were 984 blood cultures drawn for 2356 patient visits, almost halving the number of blood cultures per patient day.
Comparing the pre- and post-intervention periods, there was no statistical difference in the occurrence of septic shock, hospital mortality, or hospital readmission.
Dr Milstone said this means patients experienced no increased risk of a missed sepsis diagnosis because of the intervention.
He and his colleagues said the future directions of this research include further exploring the implications this intervention may have for antibiotic use as well as working to implement the tools in other ICUs. The tools are already being tried at Johns Hopkins All Children’s Hospital in Florida and in the pediatric ICU at the University of Virginia.
for a child in the pediatric ICU
Photo courtesy of
Johns Hopkins Medicine
New research suggests clinical practice guidelines can reduce the number of potentially unnecessary blood culture draws in critically ill children without endangering doctors’ ability to diagnose and treat sepsis.
The guidelines consist of 2 documents—a screening checklist and a decision algorithm.
In a single-center study, clinicians consulted these documents when considering ordering blood cultures for patients in a pediatric intensive care unit (ICU).
The clinicians said there was an immediate reduction in unnecessary blood draws after they began using these guidelines, and they were able to sustain the reduction over time.
Aaron Milstone, MD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues described these results in JAMA Pediatrics.
The guidelines were created by a team of nurses, vascular access specialists, and physicians across specialties. The team created a fever/sepsis screening checklist and an accompanying decision-making flow chart designed to guide clinicians in the decision to draw blood.
These tools were posted in the pediatric ICU at The Johns Hopkins Hospital with instructions to be completed at the bedside by nurses and physicians. Each week, the team would meet to evaluate the data gathered, review how many cultures were sent from the unit, and discuss in detail individual cases where blood draws were necessary.
The researchers compared patient length of stay, mortality, readmission, and the number of episodes of suspected septic shock at the hospital before and after this intervention was implemented.
In the year before the team introduced the tools, there were 2204 patient visits to the pediatric ICU and 1807 blood cultures drawn.
After the intervention, there were 984 blood cultures drawn for 2356 patient visits, almost halving the number of blood cultures per patient day.
Comparing the pre- and post-intervention periods, there was no statistical difference in the occurrence of septic shock, hospital mortality, or hospital readmission.
Dr Milstone said this means patients experienced no increased risk of a missed sepsis diagnosis because of the intervention.
He and his colleagues said the future directions of this research include further exploring the implications this intervention may have for antibiotic use as well as working to implement the tools in other ICUs. The tools are already being tried at Johns Hopkins All Children’s Hospital in Florida and in the pediatric ICU at the University of Virginia.
Company terminates study of drug for MM
multiple myeloma
BioInvent International has decided to terminate its phase 2 trial of the antibody BI-505 in patients with multiple myeloma (MM).
The decision follows a review and discussion with the US Food and Drug Administration (FDA), which put the trial on full clinical hold in November due to an adverse cardiopulmonary event.
The trial was designed to determine if BI-505 could deepen therapeutic response and thereby prevent or delay relapse in MM patients undergoing autologous stem cell transplant with high-dose melphalan.
The termination of this trial may not mean the end of BI-505. BioInvent is currently in discussions with the FDA about the potential to develop the drug for use in other patient populations.
BI-505 is a human antibody targeting ICAM-1, a protein that is elevated in MM cells. BI-505 has been shown to attack MM in 2 ways—by inducing apoptosis in MM cells and by engaging macrophages to attack and kill MM cells.
The development strategy for BI-505 has been focused on eliminating residual disease by combining the antibody with modern standard-of-care drugs used to treat MM.
BI-505 has orphan drug designation as a treatment for MM from both the FDA and the European Medicines Agency.
Results of a phase 1 trial of BI-505 in MM patients were published in Clinical Cancer Research in June 2015.
multiple myeloma
BioInvent International has decided to terminate its phase 2 trial of the antibody BI-505 in patients with multiple myeloma (MM).
The decision follows a review and discussion with the US Food and Drug Administration (FDA), which put the trial on full clinical hold in November due to an adverse cardiopulmonary event.
The trial was designed to determine if BI-505 could deepen therapeutic response and thereby prevent or delay relapse in MM patients undergoing autologous stem cell transplant with high-dose melphalan.
The termination of this trial may not mean the end of BI-505. BioInvent is currently in discussions with the FDA about the potential to develop the drug for use in other patient populations.
BI-505 is a human antibody targeting ICAM-1, a protein that is elevated in MM cells. BI-505 has been shown to attack MM in 2 ways—by inducing apoptosis in MM cells and by engaging macrophages to attack and kill MM cells.
The development strategy for BI-505 has been focused on eliminating residual disease by combining the antibody with modern standard-of-care drugs used to treat MM.
BI-505 has orphan drug designation as a treatment for MM from both the FDA and the European Medicines Agency.
Results of a phase 1 trial of BI-505 in MM patients were published in Clinical Cancer Research in June 2015.
multiple myeloma
BioInvent International has decided to terminate its phase 2 trial of the antibody BI-505 in patients with multiple myeloma (MM).
The decision follows a review and discussion with the US Food and Drug Administration (FDA), which put the trial on full clinical hold in November due to an adverse cardiopulmonary event.
The trial was designed to determine if BI-505 could deepen therapeutic response and thereby prevent or delay relapse in MM patients undergoing autologous stem cell transplant with high-dose melphalan.
The termination of this trial may not mean the end of BI-505. BioInvent is currently in discussions with the FDA about the potential to develop the drug for use in other patient populations.
BI-505 is a human antibody targeting ICAM-1, a protein that is elevated in MM cells. BI-505 has been shown to attack MM in 2 ways—by inducing apoptosis in MM cells and by engaging macrophages to attack and kill MM cells.
The development strategy for BI-505 has been focused on eliminating residual disease by combining the antibody with modern standard-of-care drugs used to treat MM.
BI-505 has orphan drug designation as a treatment for MM from both the FDA and the European Medicines Agency.
Results of a phase 1 trial of BI-505 in MM patients were published in Clinical Cancer Research in June 2015.