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Group detects new steps in hematopoiesis
in the bone marrow
Researchers say they have discovered previously undetected steps in hematopoiesis, establishing that a highly complex series of events determine the fate of closely related populations of blood progenitor cells.
Their study revealed thousands of differences in gene expression between blood cell types.
These differences result from many specific events that are crucial for normal blood development, and errors in this process can lead to blood disorders.
The researchers described their work in Science.
The team sequenced RNA from 8 primary human hematopoietic progenitor populations representing the classical myeloid commitment stages of hematopoiesis and the main lymphoid stage.
This revealed 6711 genes and 10,724 transcripts enriched in non-protein-coding elements at early stages of differentiation.
The researchers also discovered the extent to which RNA is cut and pasted together in different ways during hematopoiesis, leading to specific forms of proteins for each of these stages.
“We have identified thousands of novel places where the RNA is processed in an alternative way,” said study author Willem Ouwehand, MD, PhD, of the University of Cambridge in the UK.
Specifically, the team identified 7881 novel splice junctions and 2301 differentially used alternative splicing events enriched in genes involved in regulatory processes.
“Such events changed the amount, structure, and behavior of proteins derived from a single gene,” said study author Wendy Erber, MD, DPhil, of the University of Western Australia in Crawley.
“Alternative proteins could drive stem cells towards becoming different mature blood cells.”
Until this study, hematopoiesis was relatively well understood at the level of DNA. What was not known was how the genetic information in DNA was then transcribed to generate RNA, leading to protein formation.
The researchers illustrated the importance of alternative RNA splicing in blood cell development by studying the role that 2 different forms of the same transcription factor—NFIB—play in megakaryocyte formation.
The team said their findings could have significant applications for patients with blood disorders. The results could aid the design of diagnostics and new therapies, as well as prove valuable for studies in stem cell transplant and for discovering the genetic basis of rare, inherited hematologic disorders. 
in the bone marrow
Researchers say they have discovered previously undetected steps in hematopoiesis, establishing that a highly complex series of events determine the fate of closely related populations of blood progenitor cells.
Their study revealed thousands of differences in gene expression between blood cell types.
These differences result from many specific events that are crucial for normal blood development, and errors in this process can lead to blood disorders.
The researchers described their work in Science.
The team sequenced RNA from 8 primary human hematopoietic progenitor populations representing the classical myeloid commitment stages of hematopoiesis and the main lymphoid stage.
This revealed 6711 genes and 10,724 transcripts enriched in non-protein-coding elements at early stages of differentiation.
The researchers also discovered the extent to which RNA is cut and pasted together in different ways during hematopoiesis, leading to specific forms of proteins for each of these stages.
“We have identified thousands of novel places where the RNA is processed in an alternative way,” said study author Willem Ouwehand, MD, PhD, of the University of Cambridge in the UK.
Specifically, the team identified 7881 novel splice junctions and 2301 differentially used alternative splicing events enriched in genes involved in regulatory processes.
“Such events changed the amount, structure, and behavior of proteins derived from a single gene,” said study author Wendy Erber, MD, DPhil, of the University of Western Australia in Crawley.
“Alternative proteins could drive stem cells towards becoming different mature blood cells.”
Until this study, hematopoiesis was relatively well understood at the level of DNA. What was not known was how the genetic information in DNA was then transcribed to generate RNA, leading to protein formation.
The researchers illustrated the importance of alternative RNA splicing in blood cell development by studying the role that 2 different forms of the same transcription factor—NFIB—play in megakaryocyte formation.
The team said their findings could have significant applications for patients with blood disorders. The results could aid the design of diagnostics and new therapies, as well as prove valuable for studies in stem cell transplant and for discovering the genetic basis of rare, inherited hematologic disorders.
in the bone marrow
Researchers say they have discovered previously undetected steps in hematopoiesis, establishing that a highly complex series of events determine the fate of closely related populations of blood progenitor cells.
Their study revealed thousands of differences in gene expression between blood cell types.
These differences result from many specific events that are crucial for normal blood development, and errors in this process can lead to blood disorders.
The researchers described their work in Science.
The team sequenced RNA from 8 primary human hematopoietic progenitor populations representing the classical myeloid commitment stages of hematopoiesis and the main lymphoid stage.
This revealed 6711 genes and 10,724 transcripts enriched in non-protein-coding elements at early stages of differentiation.
The researchers also discovered the extent to which RNA is cut and pasted together in different ways during hematopoiesis, leading to specific forms of proteins for each of these stages.
“We have identified thousands of novel places where the RNA is processed in an alternative way,” said study author Willem Ouwehand, MD, PhD, of the University of Cambridge in the UK.
Specifically, the team identified 7881 novel splice junctions and 2301 differentially used alternative splicing events enriched in genes involved in regulatory processes.
“Such events changed the amount, structure, and behavior of proteins derived from a single gene,” said study author Wendy Erber, MD, DPhil, of the University of Western Australia in Crawley.
“Alternative proteins could drive stem cells towards becoming different mature blood cells.”
Until this study, hematopoiesis was relatively well understood at the level of DNA. What was not known was how the genetic information in DNA was then transcribed to generate RNA, leading to protein formation.
The researchers illustrated the importance of alternative RNA splicing in blood cell development by studying the role that 2 different forms of the same transcription factor—NFIB—play in megakaryocyte formation.
The team said their findings could have significant applications for patients with blood disorders. The results could aid the design of diagnostics and new therapies, as well as prove valuable for studies in stem cell transplant and for discovering the genetic basis of rare, inherited hematologic disorders.
HHS identifies known and likely carcinogens
Credit: Trevor MacInnis
The US Department of Health and Human Services (HHS) has identified 1 chemical substance as a known human carcinogen and 3 additional substances as likely carcinogens.
Ortho-toluidine, which is used to make rubber chemicals, pesticides, and dyes, has been shown to cause urinary bladder cancer and is now listed as a known human carcinogen.
The 3 substances that are likely to be human carcinogens are 1-bromopropane, cumene, and pentachlorophenol.
1-bromopropane is used as a cleaning solvent and spray adhesive. Cumene is used to make phenol and acetone, and it is found in fuel products and tobacco smoke. Pentachlorophenol is a mixture used to preserve wood.
Exposure to pentachlorophenol is associated with an increased risk of non-Hodgkin lymphoma in humans and solid tumor malignancies in mice. Cumene and 1-bromopropane have been linked to solid tumor malignancies in mice as well.
All 4 substances are listed in the HHS’s 13th Report on Carcinogens, a science-based document prepared by the National Toxicology Program (NTP) that identifies chemical, biological, and physical agents considered to be cancer hazards for people living in the US.
The new report has a total of 243 listings, which includes known carcinogens and substances “reasonably anticipated” to be carcinogens.
“Identifying substances in our environment that can make people vulnerable to cancer will help in prevention efforts,” said Linda Birnbaum, PhD, director of the National Institute of Environmental Health Sciences and the NTP.
“This report provides a valuable resource for health regulatory and research agencies, and it empowers the public with information people can use to reduce exposure to cancer-causing substances.”
New known carcinogen
Since 1983, ortho-toluidine has been listed in the HHS’s Report on Carcinogens as reasonably anticipated to be a human carcinogen. However, new cancer studies led the NTP to reevaluate and reclassify ortho-toluidine. It is now classified as a known human carcinogen, based on clinical studies showing it causes urinary bladder cancer.
Ortho-toluidine is a synthetic chemical produced in other countries and imported into the US by several companies in high volumes. It is primarily used to make rubber chemicals, pesticides, and dyes. It is also used in some consumer and medical products.
People are mainly exposed through the workplace, by skin contact and/or inhalation when using ortho-toluidine. They can also be exposed outside the workplace through sources such as tobacco smoke.
Three new substances likely to be carcinogenic
Pentachlorophenol
Pentachlorophenol and byproducts of its synthesis are complex mixtures of chemicals used as wood preservatives. Because virtually everyone exposed to pentachlorophenol is also exposed to its synthesis byproducts, they were evaluated together.
In the US, pentachlorophenol has been regulated since the 1980s as a restricted-use pesticide. It is used industrially for treating utility poles, wood pilings, fence posts, and lumber or timber for construction.
Most exposure has occurred in settings where workers treat lumber or come in contact with treated lumber. People may also be exposed to this mixture from breathing contaminated air or dust, or from contact with contaminated soil.
Exposure to this mixture was associated with an increased risk of non-Hodgkin lymphoma in clinical studies. In mice, it has been shown to cause tumors in the liver and other organs.
1-bromopropane
1-bromopropane is a liquid used as a solvent in many commercial industries. It is used as a cleaner for optics, electronics, and metals, as well as a solvent for aerosol-applied adhesives such as those used in foam cushion manufacturing.
It is also used in dry cleaning and in solvent sprays for aircraft maintenance. Workers in certain occupations may be more exposed to 1-bromopropane than the general population.
The NTP did not identify any clinical studies that evaluated the relationship between human cancer and exposure to 1-bromopropane. However, inhalation exposure to 1-bromopropane in rodents caused tumors in several organs, including the skin, lungs, and large intestine.
Cumene
Cumene is a flammable and volatile liquid with a gasoline-like odor. It is a natural component of coal tar and petroleum, and is found in tobacco smoke. It is used primarily to make acetone and phenol.
People are mainly exposed to cumene through the environment and in workplaces that use or produce cumene. It can be found in emissions from petroleum products.
Inhalation exposure to cumene caused lung tumors in male and female mice, and liver tumors in female mice. The NTP did not identify any clinical studies evaluating the relationship between cancer and exposure to cumene.
Credit: Trevor MacInnis
The US Department of Health and Human Services (HHS) has identified 1 chemical substance as a known human carcinogen and 3 additional substances as likely carcinogens.
Ortho-toluidine, which is used to make rubber chemicals, pesticides, and dyes, has been shown to cause urinary bladder cancer and is now listed as a known human carcinogen.
The 3 substances that are likely to be human carcinogens are 1-bromopropane, cumene, and pentachlorophenol.
1-bromopropane is used as a cleaning solvent and spray adhesive. Cumene is used to make phenol and acetone, and it is found in fuel products and tobacco smoke. Pentachlorophenol is a mixture used to preserve wood.
Exposure to pentachlorophenol is associated with an increased risk of non-Hodgkin lymphoma in humans and solid tumor malignancies in mice. Cumene and 1-bromopropane have been linked to solid tumor malignancies in mice as well.
All 4 substances are listed in the HHS’s 13th Report on Carcinogens, a science-based document prepared by the National Toxicology Program (NTP) that identifies chemical, biological, and physical agents considered to be cancer hazards for people living in the US.
The new report has a total of 243 listings, which includes known carcinogens and substances “reasonably anticipated” to be carcinogens.
“Identifying substances in our environment that can make people vulnerable to cancer will help in prevention efforts,” said Linda Birnbaum, PhD, director of the National Institute of Environmental Health Sciences and the NTP.
“This report provides a valuable resource for health regulatory and research agencies, and it empowers the public with information people can use to reduce exposure to cancer-causing substances.”
New known carcinogen
Since 1983, ortho-toluidine has been listed in the HHS’s Report on Carcinogens as reasonably anticipated to be a human carcinogen. However, new cancer studies led the NTP to reevaluate and reclassify ortho-toluidine. It is now classified as a known human carcinogen, based on clinical studies showing it causes urinary bladder cancer.
Ortho-toluidine is a synthetic chemical produced in other countries and imported into the US by several companies in high volumes. It is primarily used to make rubber chemicals, pesticides, and dyes. It is also used in some consumer and medical products.
People are mainly exposed through the workplace, by skin contact and/or inhalation when using ortho-toluidine. They can also be exposed outside the workplace through sources such as tobacco smoke.
Three new substances likely to be carcinogenic
Pentachlorophenol
Pentachlorophenol and byproducts of its synthesis are complex mixtures of chemicals used as wood preservatives. Because virtually everyone exposed to pentachlorophenol is also exposed to its synthesis byproducts, they were evaluated together.
In the US, pentachlorophenol has been regulated since the 1980s as a restricted-use pesticide. It is used industrially for treating utility poles, wood pilings, fence posts, and lumber or timber for construction.
Most exposure has occurred in settings where workers treat lumber or come in contact with treated lumber. People may also be exposed to this mixture from breathing contaminated air or dust, or from contact with contaminated soil.
Exposure to this mixture was associated with an increased risk of non-Hodgkin lymphoma in clinical studies. In mice, it has been shown to cause tumors in the liver and other organs.
1-bromopropane
1-bromopropane is a liquid used as a solvent in many commercial industries. It is used as a cleaner for optics, electronics, and metals, as well as a solvent for aerosol-applied adhesives such as those used in foam cushion manufacturing.
It is also used in dry cleaning and in solvent sprays for aircraft maintenance. Workers in certain occupations may be more exposed to 1-bromopropane than the general population.
The NTP did not identify any clinical studies that evaluated the relationship between human cancer and exposure to 1-bromopropane. However, inhalation exposure to 1-bromopropane in rodents caused tumors in several organs, including the skin, lungs, and large intestine.
Cumene
Cumene is a flammable and volatile liquid with a gasoline-like odor. It is a natural component of coal tar and petroleum, and is found in tobacco smoke. It is used primarily to make acetone and phenol.
People are mainly exposed to cumene through the environment and in workplaces that use or produce cumene. It can be found in emissions from petroleum products.
Inhalation exposure to cumene caused lung tumors in male and female mice, and liver tumors in female mice. The NTP did not identify any clinical studies evaluating the relationship between cancer and exposure to cumene.
Credit: Trevor MacInnis
The US Department of Health and Human Services (HHS) has identified 1 chemical substance as a known human carcinogen and 3 additional substances as likely carcinogens.
Ortho-toluidine, which is used to make rubber chemicals, pesticides, and dyes, has been shown to cause urinary bladder cancer and is now listed as a known human carcinogen.
The 3 substances that are likely to be human carcinogens are 1-bromopropane, cumene, and pentachlorophenol.
1-bromopropane is used as a cleaning solvent and spray adhesive. Cumene is used to make phenol and acetone, and it is found in fuel products and tobacco smoke. Pentachlorophenol is a mixture used to preserve wood.
Exposure to pentachlorophenol is associated with an increased risk of non-Hodgkin lymphoma in humans and solid tumor malignancies in mice. Cumene and 1-bromopropane have been linked to solid tumor malignancies in mice as well.
All 4 substances are listed in the HHS’s 13th Report on Carcinogens, a science-based document prepared by the National Toxicology Program (NTP) that identifies chemical, biological, and physical agents considered to be cancer hazards for people living in the US.
The new report has a total of 243 listings, which includes known carcinogens and substances “reasonably anticipated” to be carcinogens.
“Identifying substances in our environment that can make people vulnerable to cancer will help in prevention efforts,” said Linda Birnbaum, PhD, director of the National Institute of Environmental Health Sciences and the NTP.
“This report provides a valuable resource for health regulatory and research agencies, and it empowers the public with information people can use to reduce exposure to cancer-causing substances.”
New known carcinogen
Since 1983, ortho-toluidine has been listed in the HHS’s Report on Carcinogens as reasonably anticipated to be a human carcinogen. However, new cancer studies led the NTP to reevaluate and reclassify ortho-toluidine. It is now classified as a known human carcinogen, based on clinical studies showing it causes urinary bladder cancer.
Ortho-toluidine is a synthetic chemical produced in other countries and imported into the US by several companies in high volumes. It is primarily used to make rubber chemicals, pesticides, and dyes. It is also used in some consumer and medical products.
People are mainly exposed through the workplace, by skin contact and/or inhalation when using ortho-toluidine. They can also be exposed outside the workplace through sources such as tobacco smoke.
Three new substances likely to be carcinogenic
Pentachlorophenol
Pentachlorophenol and byproducts of its synthesis are complex mixtures of chemicals used as wood preservatives. Because virtually everyone exposed to pentachlorophenol is also exposed to its synthesis byproducts, they were evaluated together.
In the US, pentachlorophenol has been regulated since the 1980s as a restricted-use pesticide. It is used industrially for treating utility poles, wood pilings, fence posts, and lumber or timber for construction.
Most exposure has occurred in settings where workers treat lumber or come in contact with treated lumber. People may also be exposed to this mixture from breathing contaminated air or dust, or from contact with contaminated soil.
Exposure to this mixture was associated with an increased risk of non-Hodgkin lymphoma in clinical studies. In mice, it has been shown to cause tumors in the liver and other organs.
1-bromopropane
1-bromopropane is a liquid used as a solvent in many commercial industries. It is used as a cleaner for optics, electronics, and metals, as well as a solvent for aerosol-applied adhesives such as those used in foam cushion manufacturing.
It is also used in dry cleaning and in solvent sprays for aircraft maintenance. Workers in certain occupations may be more exposed to 1-bromopropane than the general population.
The NTP did not identify any clinical studies that evaluated the relationship between human cancer and exposure to 1-bromopropane. However, inhalation exposure to 1-bromopropane in rodents caused tumors in several organs, including the skin, lungs, and large intestine.
Cumene
Cumene is a flammable and volatile liquid with a gasoline-like odor. It is a natural component of coal tar and petroleum, and is found in tobacco smoke. It is used primarily to make acetone and phenol.
People are mainly exposed to cumene through the environment and in workplaces that use or produce cumene. It can be found in emissions from petroleum products.
Inhalation exposure to cumene caused lung tumors in male and female mice, and liver tumors in female mice. The NTP did not identify any clinical studies evaluating the relationship between cancer and exposure to cumene.
Cancer treatment during pregnancy can be safe
MADRID—Two new studies suggest that children exposed to chemotherapy or radiotherapy in the womb can be spared negative long-term effects.
At a median age of 6, most of the children exposed to radiation in utero had neuropsychological, behavioral, and general health outcomes that were within normal ranges.
And children who were exposed to chemotherapy in the womb had normal mental and cardiac health at a median age of 2.
“When chemotherapy is administered after the first trimester of pregnancy, we cannot discern any problems in the children,” said Frederic Amant, MD, PhD, of University Hospitals Leuven in Belgium.
“Fear about the risks of chemotherapy administration should not be a reason to terminate a pregnancy, delay cancer treatment for the mother, or to deliver a baby prematurely.”
Dr Amant and his colleagues presented these findings (abstract 267PD_PR) and their findings on radiation (abstract 49LBA_PR) at the ESMO 2014 Congress.
Outcomes with chemotherapy
In the first study, the researchers recruited 38 children from the International Network for Cancer, Infertility and Pregnancy registry who were prenatally exposed to chemotherapy.
Most of the mothers had breast (61%) or hematologic (22%) cancers. Most were treated with anthracyclines (61%) and had received an average of 4 cycles (range, 1-7) of treatment.
The researchers assessed mental development and cardiac health in the children of these subjects, comparing them to 38 control children who were not exposed to chemotherapy.
At a median age of almost 2 years, mental development was in the normal range for both groups of children, and development was not significantly different between the groups. The mean Mental Development Index score was 99.13 for exposed children and 101.47 for controls.
Cardiac dimensions and functions were within normal ranges for both groups as well. Mean fractional shortening was 36% (range, 32-42) for exposed children and 39% (range, 32-51) for controls. Although the difference was signficant (P=0.004), the researchers said it was not clinically relevant.
“This paper points to the very important issue of long-term safety of prenatal exposure to chemotherapy and reinforces the notion that chemotherapy during gestation does not endanger the fetus and her or his subsequent development,” said Fedro Alessandro Peccatori, MD, PhD, of the European Institute of Oncology in Milan, Italy, who was not involved in this study.
“To further ameliorate neonatal outcome, a special effort should be made to prolong pregnancy duration, and stringent long-term follow-up should be pursued to confirm these findings. Meanwhile, specific measures to support prematurely delivered babies and their families should be implemented.”
Dr Amant said future studies will explore the effects of specific chemotherapy types in detail and include longer-term follow-up.
Outcomes with radiation
In a second study, Dr Amant and his colleagues explored the impact of radiotherapy on the children of women with cancer.
The study included 16 children, with a median age of 6 years, who had been exposed to radiotherapy in utero. The median maternal irradiation was 48 Gy (range, 12-70), and the median estimated fetal irradiation was 91 mGy (range, 0-1690).
Neuropsychological, behavioral, and general health outcomes were within normal ranges for most of the children. And the researchers found no linear relationship between the fetal dose of radiation and cognitive outcome.
However, there was a negative linear relationship between the gestational age at radiotherapy exposure and verbal intelligence, based on results in 8 children. Two of these children were exposed to radiotherapy in the third trimester and had verbal intelligence scores outside the normal range.
One of the 2 children had low scores on all variables of cognitive development, but other pregnancy-related complications are confounding factors. The child’s mother suffered from an aggressive non-Hodgkin tumor of the brain that impacted her general state, and she had a preterm delivery.
Dr Amant noted that this is based on a very small number of children, so the results should be interpreted with caution.
“We cannot exclude that there might be an impact of prenatal radiotherapy exposure,” he said, “but larger series are needed to further investigate this relationship.” 
MADRID—Two new studies suggest that children exposed to chemotherapy or radiotherapy in the womb can be spared negative long-term effects.
At a median age of 6, most of the children exposed to radiation in utero had neuropsychological, behavioral, and general health outcomes that were within normal ranges.
And children who were exposed to chemotherapy in the womb had normal mental and cardiac health at a median age of 2.
“When chemotherapy is administered after the first trimester of pregnancy, we cannot discern any problems in the children,” said Frederic Amant, MD, PhD, of University Hospitals Leuven in Belgium.
“Fear about the risks of chemotherapy administration should not be a reason to terminate a pregnancy, delay cancer treatment for the mother, or to deliver a baby prematurely.”
Dr Amant and his colleagues presented these findings (abstract 267PD_PR) and their findings on radiation (abstract 49LBA_PR) at the ESMO 2014 Congress.
Outcomes with chemotherapy
In the first study, the researchers recruited 38 children from the International Network for Cancer, Infertility and Pregnancy registry who were prenatally exposed to chemotherapy.
Most of the mothers had breast (61%) or hematologic (22%) cancers. Most were treated with anthracyclines (61%) and had received an average of 4 cycles (range, 1-7) of treatment.
The researchers assessed mental development and cardiac health in the children of these subjects, comparing them to 38 control children who were not exposed to chemotherapy.
At a median age of almost 2 years, mental development was in the normal range for both groups of children, and development was not significantly different between the groups. The mean Mental Development Index score was 99.13 for exposed children and 101.47 for controls.
Cardiac dimensions and functions were within normal ranges for both groups as well. Mean fractional shortening was 36% (range, 32-42) for exposed children and 39% (range, 32-51) for controls. Although the difference was signficant (P=0.004), the researchers said it was not clinically relevant.
“This paper points to the very important issue of long-term safety of prenatal exposure to chemotherapy and reinforces the notion that chemotherapy during gestation does not endanger the fetus and her or his subsequent development,” said Fedro Alessandro Peccatori, MD, PhD, of the European Institute of Oncology in Milan, Italy, who was not involved in this study.
“To further ameliorate neonatal outcome, a special effort should be made to prolong pregnancy duration, and stringent long-term follow-up should be pursued to confirm these findings. Meanwhile, specific measures to support prematurely delivered babies and their families should be implemented.”
Dr Amant said future studies will explore the effects of specific chemotherapy types in detail and include longer-term follow-up.
Outcomes with radiation
In a second study, Dr Amant and his colleagues explored the impact of radiotherapy on the children of women with cancer.
The study included 16 children, with a median age of 6 years, who had been exposed to radiotherapy in utero. The median maternal irradiation was 48 Gy (range, 12-70), and the median estimated fetal irradiation was 91 mGy (range, 0-1690).
Neuropsychological, behavioral, and general health outcomes were within normal ranges for most of the children. And the researchers found no linear relationship between the fetal dose of radiation and cognitive outcome.
However, there was a negative linear relationship between the gestational age at radiotherapy exposure and verbal intelligence, based on results in 8 children. Two of these children were exposed to radiotherapy in the third trimester and had verbal intelligence scores outside the normal range.
One of the 2 children had low scores on all variables of cognitive development, but other pregnancy-related complications are confounding factors. The child’s mother suffered from an aggressive non-Hodgkin tumor of the brain that impacted her general state, and she had a preterm delivery.
Dr Amant noted that this is based on a very small number of children, so the results should be interpreted with caution.
“We cannot exclude that there might be an impact of prenatal radiotherapy exposure,” he said, “but larger series are needed to further investigate this relationship.”
MADRID—Two new studies suggest that children exposed to chemotherapy or radiotherapy in the womb can be spared negative long-term effects.
At a median age of 6, most of the children exposed to radiation in utero had neuropsychological, behavioral, and general health outcomes that were within normal ranges.
And children who were exposed to chemotherapy in the womb had normal mental and cardiac health at a median age of 2.
“When chemotherapy is administered after the first trimester of pregnancy, we cannot discern any problems in the children,” said Frederic Amant, MD, PhD, of University Hospitals Leuven in Belgium.
“Fear about the risks of chemotherapy administration should not be a reason to terminate a pregnancy, delay cancer treatment for the mother, or to deliver a baby prematurely.”
Dr Amant and his colleagues presented these findings (abstract 267PD_PR) and their findings on radiation (abstract 49LBA_PR) at the ESMO 2014 Congress.
Outcomes with chemotherapy
In the first study, the researchers recruited 38 children from the International Network for Cancer, Infertility and Pregnancy registry who were prenatally exposed to chemotherapy.
Most of the mothers had breast (61%) or hematologic (22%) cancers. Most were treated with anthracyclines (61%) and had received an average of 4 cycles (range, 1-7) of treatment.
The researchers assessed mental development and cardiac health in the children of these subjects, comparing them to 38 control children who were not exposed to chemotherapy.
At a median age of almost 2 years, mental development was in the normal range for both groups of children, and development was not significantly different between the groups. The mean Mental Development Index score was 99.13 for exposed children and 101.47 for controls.
Cardiac dimensions and functions were within normal ranges for both groups as well. Mean fractional shortening was 36% (range, 32-42) for exposed children and 39% (range, 32-51) for controls. Although the difference was signficant (P=0.004), the researchers said it was not clinically relevant.
“This paper points to the very important issue of long-term safety of prenatal exposure to chemotherapy and reinforces the notion that chemotherapy during gestation does not endanger the fetus and her or his subsequent development,” said Fedro Alessandro Peccatori, MD, PhD, of the European Institute of Oncology in Milan, Italy, who was not involved in this study.
“To further ameliorate neonatal outcome, a special effort should be made to prolong pregnancy duration, and stringent long-term follow-up should be pursued to confirm these findings. Meanwhile, specific measures to support prematurely delivered babies and their families should be implemented.”
Dr Amant said future studies will explore the effects of specific chemotherapy types in detail and include longer-term follow-up.
Outcomes with radiation
In a second study, Dr Amant and his colleagues explored the impact of radiotherapy on the children of women with cancer.
The study included 16 children, with a median age of 6 years, who had been exposed to radiotherapy in utero. The median maternal irradiation was 48 Gy (range, 12-70), and the median estimated fetal irradiation was 91 mGy (range, 0-1690).
Neuropsychological, behavioral, and general health outcomes were within normal ranges for most of the children. And the researchers found no linear relationship between the fetal dose of radiation and cognitive outcome.
However, there was a negative linear relationship between the gestational age at radiotherapy exposure and verbal intelligence, based on results in 8 children. Two of these children were exposed to radiotherapy in the third trimester and had verbal intelligence scores outside the normal range.
One of the 2 children had low scores on all variables of cognitive development, but other pregnancy-related complications are confounding factors. The child’s mother suffered from an aggressive non-Hodgkin tumor of the brain that impacted her general state, and she had a preterm delivery.
Dr Amant noted that this is based on a very small number of children, so the results should be interpreted with caution.
“We cannot exclude that there might be an impact of prenatal radiotherapy exposure,” he said, “but larger series are needed to further investigate this relationship.”
Five genes linked to risk of severe malaria
Credit: Peter H. Seeberger
Investigators have identified 5 genes that appear to affect a person’s susceptibility to severe malaria.
The group’s analyses suggest that single-nucleotide polymorphisms (SNPs) in HBB, ABO, ATP2B4, G6PD, and CD40LG are associated with an increased or decreased risk of severe malaria, cerebral malaria, and severe malarial anemia.
This knowledge could lead to new therapeutics or vaccines to target severe malaria.
“[This study] has allowed for investigation of genes that influence susceptibility to malaria on a scale that has previously not been achieved,” said Sarah Dunstan, PhD, of the Oxford University Clinical Research Unit at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam.
“It involved a large number of severe malaria patients from multiple countries, which allows us to identify genes that truly have an effect on whether or not you develop severe malaria.”
Dr Dunstan and her colleagues detailed this research in Nature Genetics.
The team collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 control subjects across 12 locations in countries of Africa, Asia, and Oceania.
The researchers tested 55 SNPs in 27 gene regions that were associated with severe malaria in previous research: ABO, ADORA2B, ATP2B4, C6, CD36, CD40LG, CR1, ACKR1 (DARC), G6PD, GNAS, HBB, ICAM1, IL1A, IL1B, IL4, IL10, IL13, IL22, IRF1, LTA, NOS2, SPTB, TLR1, TLR4, TLR6, TLR9, and TNF.
The team found evidence of associations with the HBB, ABO, ATP2B4, G6PD, and CD40LG loci, but no association for the other 22 loci.
HBB
The HBB gene encodes β-globin, which has 3 variants associated with resistance to malaria: hemoglobin S (HbS), hemoglobin C (HbC), and hemoglobin E (HbE). The SNP responsible for HbE, rs33950507, was rare or absent in most groups, so the sample was too small to estimate association with severe malaria.
However, for HbS (SNP rs334), heterozygotes had a reduced risk of severe malaria (odds ratio [OR]=0.14; P=1.6×10−225), cerebral malaria (OR=0.11; P=4.7×10−88), and severe malarial anemia (OR=0.11; P=9.3×10−65).
For HbC (SNP rs33930165), each copy of the derived allele reduced the risk of severe malaria by 29% (OR=0.71; P=6.9×10−9), cerebral malaria by 28% (OR=0.72; P=0.01), and severe malarial anemia by 26% (OR=0.74; P=2.1×10−3).
ABO
The ABO gene encodes the glycosyltransferase enzyme that determines ABO blood group. Blood group O was associated with a lower risk of severe malaria (OR=0.74; P=5.0×10−32), cerebral malaria (OR=0.73; P=8.9×10−16), and severe malarial anemia (OR=0.68; P=7.9×10−14).
The researchers also found that rs8176746, an SNP in ABO that determines the production of B antigens, was associated with an increased risk of severe malaria (OR=1.25; P=2.0×10−17).
G6PD
G6PD is an X-linked gene encoding glucose-6-phosphate dehydrogenase. The investigators found that deficiency in G6PD (rs1050828 [G6PD c.202C>T]) can reduce the risk of cerebral malaria but increase the risk of severe malarial anemia.
There was an increased risk of severe malarial anemia in male hemizygotes (OR=1.49; P=3.6×10−5) and in female homozygotes (OR=1.94; P=1.9×10−3), as well as a decreased risk of cerebral malaria in female heterozygotes (OR=0.87; P=0.06) and male hemizygotes (OR=0.81; P=0.01).
ATP2B4
ATP2B4 encodes a calcium transporter found in the plasma membrane of erythrocytes. The derived alleles of rs10900585 and rs55868763 were associated with an increased risk of severe malaria, and the derived alleles of rs4951074 and rs1541255 were associated with a decreased risk.
Subjects with at least one copy of the derived allele at rs10900585 had an OR of 1.32 for severe malaria (P=1.7×10−9), and those homozygous for the derived allele at rs4951074 had an OR of 0.77 (P=7.6×10−7). Findings were similar for cerebral malaria and severe malarial anemia.
CD40LG
CD40LG is a gene on the X chromosome that has previously been associated with severe malaria. Homozygotes for the derived allele of rs3092945 had a decreased risk of severe malaria (OR=0.85; P=1.1×10−6) when the researchers analyzed data from the study sites together.
However, the results differed when they analyzed sites individually. For instance, homozygotes had a reduced risk of severe malaria in The Gambia (OR=0.54; P=2.3×10−22) and an increased risk in Kenya (OR=1.42; P=7.8×10−6).
These findings suggest the role of common human genetic disorders in severe malaria is more complex than we thought, Dr Dunstan said. But the results should enable a better understanding of the mechanisms and processes at work during progression to severe disease.
Credit: Peter H. Seeberger
Investigators have identified 5 genes that appear to affect a person’s susceptibility to severe malaria.
The group’s analyses suggest that single-nucleotide polymorphisms (SNPs) in HBB, ABO, ATP2B4, G6PD, and CD40LG are associated with an increased or decreased risk of severe malaria, cerebral malaria, and severe malarial anemia.
This knowledge could lead to new therapeutics or vaccines to target severe malaria.
“[This study] has allowed for investigation of genes that influence susceptibility to malaria on a scale that has previously not been achieved,” said Sarah Dunstan, PhD, of the Oxford University Clinical Research Unit at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam.
“It involved a large number of severe malaria patients from multiple countries, which allows us to identify genes that truly have an effect on whether or not you develop severe malaria.”
Dr Dunstan and her colleagues detailed this research in Nature Genetics.
The team collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 control subjects across 12 locations in countries of Africa, Asia, and Oceania.
The researchers tested 55 SNPs in 27 gene regions that were associated with severe malaria in previous research: ABO, ADORA2B, ATP2B4, C6, CD36, CD40LG, CR1, ACKR1 (DARC), G6PD, GNAS, HBB, ICAM1, IL1A, IL1B, IL4, IL10, IL13, IL22, IRF1, LTA, NOS2, SPTB, TLR1, TLR4, TLR6, TLR9, and TNF.
The team found evidence of associations with the HBB, ABO, ATP2B4, G6PD, and CD40LG loci, but no association for the other 22 loci.
HBB
The HBB gene encodes β-globin, which has 3 variants associated with resistance to malaria: hemoglobin S (HbS), hemoglobin C (HbC), and hemoglobin E (HbE). The SNP responsible for HbE, rs33950507, was rare or absent in most groups, so the sample was too small to estimate association with severe malaria.
However, for HbS (SNP rs334), heterozygotes had a reduced risk of severe malaria (odds ratio [OR]=0.14; P=1.6×10−225), cerebral malaria (OR=0.11; P=4.7×10−88), and severe malarial anemia (OR=0.11; P=9.3×10−65).
For HbC (SNP rs33930165), each copy of the derived allele reduced the risk of severe malaria by 29% (OR=0.71; P=6.9×10−9), cerebral malaria by 28% (OR=0.72; P=0.01), and severe malarial anemia by 26% (OR=0.74; P=2.1×10−3).
ABO
The ABO gene encodes the glycosyltransferase enzyme that determines ABO blood group. Blood group O was associated with a lower risk of severe malaria (OR=0.74; P=5.0×10−32), cerebral malaria (OR=0.73; P=8.9×10−16), and severe malarial anemia (OR=0.68; P=7.9×10−14).
The researchers also found that rs8176746, an SNP in ABO that determines the production of B antigens, was associated with an increased risk of severe malaria (OR=1.25; P=2.0×10−17).
G6PD
G6PD is an X-linked gene encoding glucose-6-phosphate dehydrogenase. The investigators found that deficiency in G6PD (rs1050828 [G6PD c.202C>T]) can reduce the risk of cerebral malaria but increase the risk of severe malarial anemia.
There was an increased risk of severe malarial anemia in male hemizygotes (OR=1.49; P=3.6×10−5) and in female homozygotes (OR=1.94; P=1.9×10−3), as well as a decreased risk of cerebral malaria in female heterozygotes (OR=0.87; P=0.06) and male hemizygotes (OR=0.81; P=0.01).
ATP2B4
ATP2B4 encodes a calcium transporter found in the plasma membrane of erythrocytes. The derived alleles of rs10900585 and rs55868763 were associated with an increased risk of severe malaria, and the derived alleles of rs4951074 and rs1541255 were associated with a decreased risk.
Subjects with at least one copy of the derived allele at rs10900585 had an OR of 1.32 for severe malaria (P=1.7×10−9), and those homozygous for the derived allele at rs4951074 had an OR of 0.77 (P=7.6×10−7). Findings were similar for cerebral malaria and severe malarial anemia.
CD40LG
CD40LG is a gene on the X chromosome that has previously been associated with severe malaria. Homozygotes for the derived allele of rs3092945 had a decreased risk of severe malaria (OR=0.85; P=1.1×10−6) when the researchers analyzed data from the study sites together.
However, the results differed when they analyzed sites individually. For instance, homozygotes had a reduced risk of severe malaria in The Gambia (OR=0.54; P=2.3×10−22) and an increased risk in Kenya (OR=1.42; P=7.8×10−6).
These findings suggest the role of common human genetic disorders in severe malaria is more complex than we thought, Dr Dunstan said. But the results should enable a better understanding of the mechanisms and processes at work during progression to severe disease.
Credit: Peter H. Seeberger
Investigators have identified 5 genes that appear to affect a person’s susceptibility to severe malaria.
The group’s analyses suggest that single-nucleotide polymorphisms (SNPs) in HBB, ABO, ATP2B4, G6PD, and CD40LG are associated with an increased or decreased risk of severe malaria, cerebral malaria, and severe malarial anemia.
This knowledge could lead to new therapeutics or vaccines to target severe malaria.
“[This study] has allowed for investigation of genes that influence susceptibility to malaria on a scale that has previously not been achieved,” said Sarah Dunstan, PhD, of the Oxford University Clinical Research Unit at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam.
“It involved a large number of severe malaria patients from multiple countries, which allows us to identify genes that truly have an effect on whether or not you develop severe malaria.”
Dr Dunstan and her colleagues detailed this research in Nature Genetics.
The team collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 control subjects across 12 locations in countries of Africa, Asia, and Oceania.
The researchers tested 55 SNPs in 27 gene regions that were associated with severe malaria in previous research: ABO, ADORA2B, ATP2B4, C6, CD36, CD40LG, CR1, ACKR1 (DARC), G6PD, GNAS, HBB, ICAM1, IL1A, IL1B, IL4, IL10, IL13, IL22, IRF1, LTA, NOS2, SPTB, TLR1, TLR4, TLR6, TLR9, and TNF.
The team found evidence of associations with the HBB, ABO, ATP2B4, G6PD, and CD40LG loci, but no association for the other 22 loci.
HBB
The HBB gene encodes β-globin, which has 3 variants associated with resistance to malaria: hemoglobin S (HbS), hemoglobin C (HbC), and hemoglobin E (HbE). The SNP responsible for HbE, rs33950507, was rare or absent in most groups, so the sample was too small to estimate association with severe malaria.
However, for HbS (SNP rs334), heterozygotes had a reduced risk of severe malaria (odds ratio [OR]=0.14; P=1.6×10−225), cerebral malaria (OR=0.11; P=4.7×10−88), and severe malarial anemia (OR=0.11; P=9.3×10−65).
For HbC (SNP rs33930165), each copy of the derived allele reduced the risk of severe malaria by 29% (OR=0.71; P=6.9×10−9), cerebral malaria by 28% (OR=0.72; P=0.01), and severe malarial anemia by 26% (OR=0.74; P=2.1×10−3).
ABO
The ABO gene encodes the glycosyltransferase enzyme that determines ABO blood group. Blood group O was associated with a lower risk of severe malaria (OR=0.74; P=5.0×10−32), cerebral malaria (OR=0.73; P=8.9×10−16), and severe malarial anemia (OR=0.68; P=7.9×10−14).
The researchers also found that rs8176746, an SNP in ABO that determines the production of B antigens, was associated with an increased risk of severe malaria (OR=1.25; P=2.0×10−17).
G6PD
G6PD is an X-linked gene encoding glucose-6-phosphate dehydrogenase. The investigators found that deficiency in G6PD (rs1050828 [G6PD c.202C>T]) can reduce the risk of cerebral malaria but increase the risk of severe malarial anemia.
There was an increased risk of severe malarial anemia in male hemizygotes (OR=1.49; P=3.6×10−5) and in female homozygotes (OR=1.94; P=1.9×10−3), as well as a decreased risk of cerebral malaria in female heterozygotes (OR=0.87; P=0.06) and male hemizygotes (OR=0.81; P=0.01).
ATP2B4
ATP2B4 encodes a calcium transporter found in the plasma membrane of erythrocytes. The derived alleles of rs10900585 and rs55868763 were associated with an increased risk of severe malaria, and the derived alleles of rs4951074 and rs1541255 were associated with a decreased risk.
Subjects with at least one copy of the derived allele at rs10900585 had an OR of 1.32 for severe malaria (P=1.7×10−9), and those homozygous for the derived allele at rs4951074 had an OR of 0.77 (P=7.6×10−7). Findings were similar for cerebral malaria and severe malarial anemia.
CD40LG
CD40LG is a gene on the X chromosome that has previously been associated with severe malaria. Homozygotes for the derived allele of rs3092945 had a decreased risk of severe malaria (OR=0.85; P=1.1×10−6) when the researchers analyzed data from the study sites together.
However, the results differed when they analyzed sites individually. For instance, homozygotes had a reduced risk of severe malaria in The Gambia (OR=0.54; P=2.3×10−22) and an increased risk in Kenya (OR=1.42; P=7.8×10−6).
These findings suggest the role of common human genetic disorders in severe malaria is more complex than we thought, Dr Dunstan said. But the results should enable a better understanding of the mechanisms and processes at work during progression to severe disease.
Drug can prevent chemo-induced nausea, vomiting
Credit: Rhoda Baer
MADRID—A small molecule called rolapitant can prevent nausea and vomiting in patients receiving cisplatin-based chemotherapy, results of a phase 3 trial suggest.
When given prior to chemotherapy, rolapitant induced a complete response in about 70% of patients.
These patients had no emesis after chemotherapy and did not require any rescue medication.
“This agent makes a significant difference in the way people tolerate their chemotherapy,” said Martin Chasen, MD, of Ottawa Hospital Cancer Centre in Canada.
“Patients experienced no loss in quality of life, and, in fact, many saw meaningful improvements. One of the patients in the rolapitant cohort reported that he had just finished 18 holes of golf one week after receiving chemotherapy. This is in sharp contrast to many patients on current standard anti-emetics that are too ill to get out of bed within a week after each cycle of cisplatin.”
Dr Chasen and his colleagues reported these results at the ESMO 2014 Congress (abstract LBA47_PR).
The team had set out to evaluate rolapitant, a novel antagonist of the NK-1 receptor, for the prevention of severe nausea and vomiting often experienced by patients receiving cisplatin-based chemotherapy, which may cause dose reductions and treatment discontinuation.
The trial included 532 patients who were randomized 1:1 to receive rolapitant plus granisetron/dexamethasone or placebo plus granisetron/dexamethasone prior to chemotherapy.
The primary endpoint was complete response (defined as the patient having no emesis and not requiring any rescue medication) in the delayed phase (>24-120 hours) post-chemotherapy. Key secondary endpoints included complete response during the acute phase (0-24 hours) and overall (0-120 hours).
The trial met its primary endpoint, with 72.7% of patients receiving rolapitant achieving a complete response in the delayed phase, compared to 58.4% of those receiving placebo (P<0.001).
Rolapitant also improved the complete response rate compared to placebo in the acute phase—83.7% and 73.7%, respectively (P=0.005).
Overall, the complete response rates were 70.1% and 56.5%, respectively (P=0.001).
Patients receiving rolapitant tended to report that chemotherapy had less of an impact on their daily quality of life, although the difference between the treatment arms was not significant—72.8% vs 67.8% (P=0.231).
“Rolapitant demonstrated a significant effect in both the acute and delayed phases,” Dr Chasen noted. “Our primary endpoint was achieved in the delayed phase—an incredible result.”
“We know that the NK-1 receptor in the brain must be blocked to control nausea and vomiting. Rolapitant is an exceptionally long-term receptor blocker that binds to the receptor and remains in place for up to 120 hours, therefore not allowing the chemotherapy to induce nausea and vomiting.”
Dr Chasen added that rolapitant may prove effective in patients receiving less emetogenic cancer treatments as well.
Credit: Rhoda Baer
MADRID—A small molecule called rolapitant can prevent nausea and vomiting in patients receiving cisplatin-based chemotherapy, results of a phase 3 trial suggest.
When given prior to chemotherapy, rolapitant induced a complete response in about 70% of patients.
These patients had no emesis after chemotherapy and did not require any rescue medication.
“This agent makes a significant difference in the way people tolerate their chemotherapy,” said Martin Chasen, MD, of Ottawa Hospital Cancer Centre in Canada.
“Patients experienced no loss in quality of life, and, in fact, many saw meaningful improvements. One of the patients in the rolapitant cohort reported that he had just finished 18 holes of golf one week after receiving chemotherapy. This is in sharp contrast to many patients on current standard anti-emetics that are too ill to get out of bed within a week after each cycle of cisplatin.”
Dr Chasen and his colleagues reported these results at the ESMO 2014 Congress (abstract LBA47_PR).
The team had set out to evaluate rolapitant, a novel antagonist of the NK-1 receptor, for the prevention of severe nausea and vomiting often experienced by patients receiving cisplatin-based chemotherapy, which may cause dose reductions and treatment discontinuation.
The trial included 532 patients who were randomized 1:1 to receive rolapitant plus granisetron/dexamethasone or placebo plus granisetron/dexamethasone prior to chemotherapy.
The primary endpoint was complete response (defined as the patient having no emesis and not requiring any rescue medication) in the delayed phase (>24-120 hours) post-chemotherapy. Key secondary endpoints included complete response during the acute phase (0-24 hours) and overall (0-120 hours).
The trial met its primary endpoint, with 72.7% of patients receiving rolapitant achieving a complete response in the delayed phase, compared to 58.4% of those receiving placebo (P<0.001).
Rolapitant also improved the complete response rate compared to placebo in the acute phase—83.7% and 73.7%, respectively (P=0.005).
Overall, the complete response rates were 70.1% and 56.5%, respectively (P=0.001).
Patients receiving rolapitant tended to report that chemotherapy had less of an impact on their daily quality of life, although the difference between the treatment arms was not significant—72.8% vs 67.8% (P=0.231).
“Rolapitant demonstrated a significant effect in both the acute and delayed phases,” Dr Chasen noted. “Our primary endpoint was achieved in the delayed phase—an incredible result.”
“We know that the NK-1 receptor in the brain must be blocked to control nausea and vomiting. Rolapitant is an exceptionally long-term receptor blocker that binds to the receptor and remains in place for up to 120 hours, therefore not allowing the chemotherapy to induce nausea and vomiting.”
Dr Chasen added that rolapitant may prove effective in patients receiving less emetogenic cancer treatments as well.
Credit: Rhoda Baer
MADRID—A small molecule called rolapitant can prevent nausea and vomiting in patients receiving cisplatin-based chemotherapy, results of a phase 3 trial suggest.
When given prior to chemotherapy, rolapitant induced a complete response in about 70% of patients.
These patients had no emesis after chemotherapy and did not require any rescue medication.
“This agent makes a significant difference in the way people tolerate their chemotherapy,” said Martin Chasen, MD, of Ottawa Hospital Cancer Centre in Canada.
“Patients experienced no loss in quality of life, and, in fact, many saw meaningful improvements. One of the patients in the rolapitant cohort reported that he had just finished 18 holes of golf one week after receiving chemotherapy. This is in sharp contrast to many patients on current standard anti-emetics that are too ill to get out of bed within a week after each cycle of cisplatin.”
Dr Chasen and his colleagues reported these results at the ESMO 2014 Congress (abstract LBA47_PR).
The team had set out to evaluate rolapitant, a novel antagonist of the NK-1 receptor, for the prevention of severe nausea and vomiting often experienced by patients receiving cisplatin-based chemotherapy, which may cause dose reductions and treatment discontinuation.
The trial included 532 patients who were randomized 1:1 to receive rolapitant plus granisetron/dexamethasone or placebo plus granisetron/dexamethasone prior to chemotherapy.
The primary endpoint was complete response (defined as the patient having no emesis and not requiring any rescue medication) in the delayed phase (>24-120 hours) post-chemotherapy. Key secondary endpoints included complete response during the acute phase (0-24 hours) and overall (0-120 hours).
The trial met its primary endpoint, with 72.7% of patients receiving rolapitant achieving a complete response in the delayed phase, compared to 58.4% of those receiving placebo (P<0.001).
Rolapitant also improved the complete response rate compared to placebo in the acute phase—83.7% and 73.7%, respectively (P=0.005).
Overall, the complete response rates were 70.1% and 56.5%, respectively (P=0.001).
Patients receiving rolapitant tended to report that chemotherapy had less of an impact on their daily quality of life, although the difference between the treatment arms was not significant—72.8% vs 67.8% (P=0.231).
“Rolapitant demonstrated a significant effect in both the acute and delayed phases,” Dr Chasen noted. “Our primary endpoint was achieved in the delayed phase—an incredible result.”
“We know that the NK-1 receptor in the brain must be blocked to control nausea and vomiting. Rolapitant is an exceptionally long-term receptor blocker that binds to the receptor and remains in place for up to 120 hours, therefore not allowing the chemotherapy to induce nausea and vomiting.”
Dr Chasen added that rolapitant may prove effective in patients receiving less emetogenic cancer treatments as well.
Rivaroxaban rivals standard for VTE in cancer
Credit: CDC
MADRID—A pooled analysis of 2 studies suggests rivaroxaban prevents recurrent venous thromboembolism (VTE) in cancer patients as effectively as standard therapy, while conferring a lower risk of major bleeding.
The analysis included data from the EINSTEIN-DVT and EINSTEIN-PE trials, which were funded by the companies developing rivaroxaban (Xarelto), Bayer HealthCare Pharmaceuticals and Janssen Research & Development, LLC.
The results were published in Lancet Haematology and presented at the ESMO 2014 Congress (abstract LBA48).
The EINSTEIN-PE study included 3449 subjects with acute symptomatic pulmonary embolism (PE), with or without symptomatic deep vein thrombosis (DVT), who received anticoagulant therapy for 6 or 12 months.
The EINSTEIN-DVT study included 4833 patients who had acute symptomatic DVT, but no symptoms of PE, and received treatment for 3, 6, or 12 months.
In both studies, patients received either oral rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) or standard therapy—enoxaparin (1.0 mg/kg twice daily) followed by a vitamin K antagonist (warfarin or acenocoumarol).
A total of 8281 patients were randomized in these studies—4150 to rivaroxaban and 4131 to standard therapy. Of the 655 patients (7.9%) with active cancer, 462 (5.6%) had cancer at baseline, and 193 (2.3%) were diagnosed during the study.
For this analysis, Martin H. Prins, MD, PhD, of Maastricht University Medical Center in The Netherlands, and his colleagues compared the 2 treatments in patients with active cancer.
VTE recurred in 4.5% (16/354) of the patients who were randomized to rivaroxaban and 6.6% (20/301) of patients randomized to standard therapy (hazard ratio [HR]=0.67).
The mortality rate was 16.4% (58/354) among patients randomized to rivaroxaban and 17.6% (53/301) among those randomized to standard therapy (HR=0.93).
Major bleeding occurred in 2.3% (8/353) of patients who received rivaroxaban and 5% (15/298) who received standard therapy (HR=0.42). And clinically relevant bleeding occurred in 13.6% (48/353) and 16.4% (49/298), respectively (HR=0.80).
Given these results, Dr Prins and his colleagues concluded that rivaroxaban can be considered an alternative to standard therapy in patients with cancer-associated VTE.
The team also said there is a need for a head-to-head comparison of rivaroxaban and long-term low-molecular-weight heparin in this patient population.
Credit: CDC
MADRID—A pooled analysis of 2 studies suggests rivaroxaban prevents recurrent venous thromboembolism (VTE) in cancer patients as effectively as standard therapy, while conferring a lower risk of major bleeding.
The analysis included data from the EINSTEIN-DVT and EINSTEIN-PE trials, which were funded by the companies developing rivaroxaban (Xarelto), Bayer HealthCare Pharmaceuticals and Janssen Research & Development, LLC.
The results were published in Lancet Haematology and presented at the ESMO 2014 Congress (abstract LBA48).
The EINSTEIN-PE study included 3449 subjects with acute symptomatic pulmonary embolism (PE), with or without symptomatic deep vein thrombosis (DVT), who received anticoagulant therapy for 6 or 12 months.
The EINSTEIN-DVT study included 4833 patients who had acute symptomatic DVT, but no symptoms of PE, and received treatment for 3, 6, or 12 months.
In both studies, patients received either oral rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) or standard therapy—enoxaparin (1.0 mg/kg twice daily) followed by a vitamin K antagonist (warfarin or acenocoumarol).
A total of 8281 patients were randomized in these studies—4150 to rivaroxaban and 4131 to standard therapy. Of the 655 patients (7.9%) with active cancer, 462 (5.6%) had cancer at baseline, and 193 (2.3%) were diagnosed during the study.
For this analysis, Martin H. Prins, MD, PhD, of Maastricht University Medical Center in The Netherlands, and his colleagues compared the 2 treatments in patients with active cancer.
VTE recurred in 4.5% (16/354) of the patients who were randomized to rivaroxaban and 6.6% (20/301) of patients randomized to standard therapy (hazard ratio [HR]=0.67).
The mortality rate was 16.4% (58/354) among patients randomized to rivaroxaban and 17.6% (53/301) among those randomized to standard therapy (HR=0.93).
Major bleeding occurred in 2.3% (8/353) of patients who received rivaroxaban and 5% (15/298) who received standard therapy (HR=0.42). And clinically relevant bleeding occurred in 13.6% (48/353) and 16.4% (49/298), respectively (HR=0.80).
Given these results, Dr Prins and his colleagues concluded that rivaroxaban can be considered an alternative to standard therapy in patients with cancer-associated VTE.
The team also said there is a need for a head-to-head comparison of rivaroxaban and long-term low-molecular-weight heparin in this patient population.
Credit: CDC
MADRID—A pooled analysis of 2 studies suggests rivaroxaban prevents recurrent venous thromboembolism (VTE) in cancer patients as effectively as standard therapy, while conferring a lower risk of major bleeding.
The analysis included data from the EINSTEIN-DVT and EINSTEIN-PE trials, which were funded by the companies developing rivaroxaban (Xarelto), Bayer HealthCare Pharmaceuticals and Janssen Research & Development, LLC.
The results were published in Lancet Haematology and presented at the ESMO 2014 Congress (abstract LBA48).
The EINSTEIN-PE study included 3449 subjects with acute symptomatic pulmonary embolism (PE), with or without symptomatic deep vein thrombosis (DVT), who received anticoagulant therapy for 6 or 12 months.
The EINSTEIN-DVT study included 4833 patients who had acute symptomatic DVT, but no symptoms of PE, and received treatment for 3, 6, or 12 months.
In both studies, patients received either oral rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) or standard therapy—enoxaparin (1.0 mg/kg twice daily) followed by a vitamin K antagonist (warfarin or acenocoumarol).
A total of 8281 patients were randomized in these studies—4150 to rivaroxaban and 4131 to standard therapy. Of the 655 patients (7.9%) with active cancer, 462 (5.6%) had cancer at baseline, and 193 (2.3%) were diagnosed during the study.
For this analysis, Martin H. Prins, MD, PhD, of Maastricht University Medical Center in The Netherlands, and his colleagues compared the 2 treatments in patients with active cancer.
VTE recurred in 4.5% (16/354) of the patients who were randomized to rivaroxaban and 6.6% (20/301) of patients randomized to standard therapy (hazard ratio [HR]=0.67).
The mortality rate was 16.4% (58/354) among patients randomized to rivaroxaban and 17.6% (53/301) among those randomized to standard therapy (HR=0.93).
Major bleeding occurred in 2.3% (8/353) of patients who received rivaroxaban and 5% (15/298) who received standard therapy (HR=0.42). And clinically relevant bleeding occurred in 13.6% (48/353) and 16.4% (49/298), respectively (HR=0.80).
Given these results, Dr Prins and his colleagues concluded that rivaroxaban can be considered an alternative to standard therapy in patients with cancer-associated VTE.
The team also said there is a need for a head-to-head comparison of rivaroxaban and long-term low-molecular-weight heparin in this patient population.
Preventing cancer-related infection
Credit: CDC/Kimberly Smith
and Christine Ford
NEW YORK—Hand washing is still the single most effective method to prevent the transmission of infection, but additional measures can reduce the risk of cancer-related infections, according to a speaker at the NCCN 9th Annual Congress: Hematologic Malignancies.
In her presentation, Laura Zitella, RN, of the Stanford Cancer Institute in California, discussed current recommendations for pharmacologic and non-pharmacologic infection prophylaxis.
She noted that NCCN Guidelines on the Prevention and Treatment of Cancer-Related Infections state that the highest risk of infection is in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), acute leukemia patients undergoing induction or consolidation therapy, patients receiving alemtuzumab therapy, patients with graft-vs-host disease (GVHD) treated with high-dose steroids, and patients with neutropenia anticipated to last greater than 10 days.
Antibiotic prophylaxis
Prior to 2005, Zitella said, no survival benefit was observed for antibiotic prophylaxis. All of this changed with the results of a meta-analysis. The analysis included 95 randomized, controlled trials and 9283 patients, the majority having acute leukemia or undergoing HSCT.
For the first time, antibiotic prophylaxis was shown to confer a survival benefit. In neutropenic patients, prophylaxis reduced overall mortality by 33% and infection-related mortality by 42%, compared with placebo or no treatment.
Prophylaxis is not recommended for low-risk neutropenic patients, Zitella said, because it is not proven to decrease morality.
And the drugs of choice are levofloxacin (500-750 mg PO daily) or ciprofloxacin (500-750 mg PO twice daily).
Colony-stimulating factors
Consensus guidelines for the use of colony-stimulating factors (CSFs) are a compilation of ASCO, EORTC, ESMO, and NCCN guidelines.
CSFs may be used prophylactically to prevent chemotherapy-induced neutropenia, febrile neutropenia, and infection. They reduce the duration of hospitalization, the duration of parenteral antibiotics, and have shown a survival benefit.
CSFs are recommended if the risk of febrile neutropenia is 20% or greater. CSFs are not routinely recommended for patients undergoing radiation treatment, acute myeloid leukemia induction, or patients with Hodgkin lymphoma.
Antifungal prophylaxis
Zitella noted that fluconazole is the best-studied antifungal prophylaxis and is recommended as the primary prophylaxis for HSCT patients.
In double-blind, placebo-controlled trials, fluconazole reduced mucosal candidiasis and invasive Candida infections in patients undergoing HSCT. And it improved survival at day 110 after transplant.
Posaconazole prophylaxis has proven effective in patients with acute myeloid leukemia or myelodysplastic syndromes undergoing intensive chemotherapy. The drug reduced invasive fungal infections, including aspergillosis, and improved survival.
For patients with GVHD on immunosuppressive therapy, posaconazole and fluconazole prophylaxis were equivalent in preventing invasive fungal infections. However, posaconazole reduced the incidence of invasive aspergillosis and fungal-related mortality.
The NCCN guidelines, Zitella said, spell out which antifungal agents should be used for each disease or therapeutic intervention.
Antiviral prophylaxis
HSV and VZV
Patients requiring antiviral prophylaxis for herpes simplex virus (HSV) and varicella zoster virus (VZV) should be seropositive and have acute leukemia, GVHD treated with steroids, prior HSV reactivation under treatment, or have undergone HSCT.
Zitella pointed out that patients treated with proteasome inhibitors, such as bortezomib, alemtuzumab, or purine analaogs, such as fludarabine, are more at risk and should also receive antiviral prophylaxis.
Recommended drugs include valacyclovir, acyclovir, or famciclovir.
CMV
Cytomegalovirus-positive (CMV+) patients at high risk include those who have received an allogeneic HSCT or treatment with alemtuzumab.
Zitella explained that for these patients, prophylaxis is uncommon, and a pre-emptive strategy should be used, including testing 3 to 6 months after transplant or in the setting of GVHD and 2 months after alemtuzumab therapy.
CMV viremia should be treated with valganciclovir, ganciclovir, foscarnet, or cidofovir.
HBV
Zitella noted that 30% of the world population has been infected with hepatitis B virus (HBV), and reactivation during cancer treatment can lead to fulminant hepatitis and death.
NCCN recommends that patients undergoing immunosuppressive therapy, allogeneic HSCT candidates, patients receiving anti-CD20 monoclonal antibodies, those treated with alemtuzumab, and patients receiving systemic therapy who have an obvious risk factor for HBV infection should be tested.
Entecavir, tenofovir, adefovir, telbivudine, or lamivudine may be used to prevent HBV reactivation.
Pneumocystis pneumonia prophylaxis
Patients undergoing allogeneic HSCT, patients with acute lymphoblastic leukemia, those treated with alemtuzumab, and those with a CD4 count below 200 cells/mcL should receive pneumocystis pneumonia prophylaxis.
Trimethorpim/sulfamethoxazole is the drug of choice. Atovaquone, dapsone, and inhaled or IV pentamidine are alternatives.
Vaccines
Zitella pointed out that recommended vaccines include influenza, pneumococcal, and tetanus, diphtheria, and acellular pertussis.
She cautioned that live attenuated vaccines should not be given to cancer patients. Other vaccines to avoid include smallpox; measles, mumps, and rubella; varicella zoster; rotavirus; yellow fever; oral typhoid; BCG; and oral polio vaccine.
Neutropenic precautions
Low microbial diets are a hot topic among patients undergoing cancer treatment, Zitella said. Fresh fruits and vegetables used to be restricted, but no studies show that dietary restrictions decrease the risk of infection.
Zitella stressed, however, that standard food safety recommendations of the USDA/FDA should be followed.
She also noted that HEPA filtration is protective against molds in high-risk patients, antiseptic bathing has contradictory evidence, the benefit of laminar airflow is unclear, and protective isolation has not been proven to reduce the risk of infection.
Credit: CDC/Kimberly Smith
and Christine Ford
NEW YORK—Hand washing is still the single most effective method to prevent the transmission of infection, but additional measures can reduce the risk of cancer-related infections, according to a speaker at the NCCN 9th Annual Congress: Hematologic Malignancies.
In her presentation, Laura Zitella, RN, of the Stanford Cancer Institute in California, discussed current recommendations for pharmacologic and non-pharmacologic infection prophylaxis.
She noted that NCCN Guidelines on the Prevention and Treatment of Cancer-Related Infections state that the highest risk of infection is in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), acute leukemia patients undergoing induction or consolidation therapy, patients receiving alemtuzumab therapy, patients with graft-vs-host disease (GVHD) treated with high-dose steroids, and patients with neutropenia anticipated to last greater than 10 days.
Antibiotic prophylaxis
Prior to 2005, Zitella said, no survival benefit was observed for antibiotic prophylaxis. All of this changed with the results of a meta-analysis. The analysis included 95 randomized, controlled trials and 9283 patients, the majority having acute leukemia or undergoing HSCT.
For the first time, antibiotic prophylaxis was shown to confer a survival benefit. In neutropenic patients, prophylaxis reduced overall mortality by 33% and infection-related mortality by 42%, compared with placebo or no treatment.
Prophylaxis is not recommended for low-risk neutropenic patients, Zitella said, because it is not proven to decrease morality.
And the drugs of choice are levofloxacin (500-750 mg PO daily) or ciprofloxacin (500-750 mg PO twice daily).
Colony-stimulating factors
Consensus guidelines for the use of colony-stimulating factors (CSFs) are a compilation of ASCO, EORTC, ESMO, and NCCN guidelines.
CSFs may be used prophylactically to prevent chemotherapy-induced neutropenia, febrile neutropenia, and infection. They reduce the duration of hospitalization, the duration of parenteral antibiotics, and have shown a survival benefit.
CSFs are recommended if the risk of febrile neutropenia is 20% or greater. CSFs are not routinely recommended for patients undergoing radiation treatment, acute myeloid leukemia induction, or patients with Hodgkin lymphoma.
Antifungal prophylaxis
Zitella noted that fluconazole is the best-studied antifungal prophylaxis and is recommended as the primary prophylaxis for HSCT patients.
In double-blind, placebo-controlled trials, fluconazole reduced mucosal candidiasis and invasive Candida infections in patients undergoing HSCT. And it improved survival at day 110 after transplant.
Posaconazole prophylaxis has proven effective in patients with acute myeloid leukemia or myelodysplastic syndromes undergoing intensive chemotherapy. The drug reduced invasive fungal infections, including aspergillosis, and improved survival.
For patients with GVHD on immunosuppressive therapy, posaconazole and fluconazole prophylaxis were equivalent in preventing invasive fungal infections. However, posaconazole reduced the incidence of invasive aspergillosis and fungal-related mortality.
The NCCN guidelines, Zitella said, spell out which antifungal agents should be used for each disease or therapeutic intervention.
Antiviral prophylaxis
HSV and VZV
Patients requiring antiviral prophylaxis for herpes simplex virus (HSV) and varicella zoster virus (VZV) should be seropositive and have acute leukemia, GVHD treated with steroids, prior HSV reactivation under treatment, or have undergone HSCT.
Zitella pointed out that patients treated with proteasome inhibitors, such as bortezomib, alemtuzumab, or purine analaogs, such as fludarabine, are more at risk and should also receive antiviral prophylaxis.
Recommended drugs include valacyclovir, acyclovir, or famciclovir.
CMV
Cytomegalovirus-positive (CMV+) patients at high risk include those who have received an allogeneic HSCT or treatment with alemtuzumab.
Zitella explained that for these patients, prophylaxis is uncommon, and a pre-emptive strategy should be used, including testing 3 to 6 months after transplant or in the setting of GVHD and 2 months after alemtuzumab therapy.
CMV viremia should be treated with valganciclovir, ganciclovir, foscarnet, or cidofovir.
HBV
Zitella noted that 30% of the world population has been infected with hepatitis B virus (HBV), and reactivation during cancer treatment can lead to fulminant hepatitis and death.
NCCN recommends that patients undergoing immunosuppressive therapy, allogeneic HSCT candidates, patients receiving anti-CD20 monoclonal antibodies, those treated with alemtuzumab, and patients receiving systemic therapy who have an obvious risk factor for HBV infection should be tested.
Entecavir, tenofovir, adefovir, telbivudine, or lamivudine may be used to prevent HBV reactivation.
Pneumocystis pneumonia prophylaxis
Patients undergoing allogeneic HSCT, patients with acute lymphoblastic leukemia, those treated with alemtuzumab, and those with a CD4 count below 200 cells/mcL should receive pneumocystis pneumonia prophylaxis.
Trimethorpim/sulfamethoxazole is the drug of choice. Atovaquone, dapsone, and inhaled or IV pentamidine are alternatives.
Vaccines
Zitella pointed out that recommended vaccines include influenza, pneumococcal, and tetanus, diphtheria, and acellular pertussis.
She cautioned that live attenuated vaccines should not be given to cancer patients. Other vaccines to avoid include smallpox; measles, mumps, and rubella; varicella zoster; rotavirus; yellow fever; oral typhoid; BCG; and oral polio vaccine.
Neutropenic precautions
Low microbial diets are a hot topic among patients undergoing cancer treatment, Zitella said. Fresh fruits and vegetables used to be restricted, but no studies show that dietary restrictions decrease the risk of infection.
Zitella stressed, however, that standard food safety recommendations of the USDA/FDA should be followed.
She also noted that HEPA filtration is protective against molds in high-risk patients, antiseptic bathing has contradictory evidence, the benefit of laminar airflow is unclear, and protective isolation has not been proven to reduce the risk of infection.
Credit: CDC/Kimberly Smith
and Christine Ford
NEW YORK—Hand washing is still the single most effective method to prevent the transmission of infection, but additional measures can reduce the risk of cancer-related infections, according to a speaker at the NCCN 9th Annual Congress: Hematologic Malignancies.
In her presentation, Laura Zitella, RN, of the Stanford Cancer Institute in California, discussed current recommendations for pharmacologic and non-pharmacologic infection prophylaxis.
She noted that NCCN Guidelines on the Prevention and Treatment of Cancer-Related Infections state that the highest risk of infection is in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), acute leukemia patients undergoing induction or consolidation therapy, patients receiving alemtuzumab therapy, patients with graft-vs-host disease (GVHD) treated with high-dose steroids, and patients with neutropenia anticipated to last greater than 10 days.
Antibiotic prophylaxis
Prior to 2005, Zitella said, no survival benefit was observed for antibiotic prophylaxis. All of this changed with the results of a meta-analysis. The analysis included 95 randomized, controlled trials and 9283 patients, the majority having acute leukemia or undergoing HSCT.
For the first time, antibiotic prophylaxis was shown to confer a survival benefit. In neutropenic patients, prophylaxis reduced overall mortality by 33% and infection-related mortality by 42%, compared with placebo or no treatment.
Prophylaxis is not recommended for low-risk neutropenic patients, Zitella said, because it is not proven to decrease morality.
And the drugs of choice are levofloxacin (500-750 mg PO daily) or ciprofloxacin (500-750 mg PO twice daily).
Colony-stimulating factors
Consensus guidelines for the use of colony-stimulating factors (CSFs) are a compilation of ASCO, EORTC, ESMO, and NCCN guidelines.
CSFs may be used prophylactically to prevent chemotherapy-induced neutropenia, febrile neutropenia, and infection. They reduce the duration of hospitalization, the duration of parenteral antibiotics, and have shown a survival benefit.
CSFs are recommended if the risk of febrile neutropenia is 20% or greater. CSFs are not routinely recommended for patients undergoing radiation treatment, acute myeloid leukemia induction, or patients with Hodgkin lymphoma.
Antifungal prophylaxis
Zitella noted that fluconazole is the best-studied antifungal prophylaxis and is recommended as the primary prophylaxis for HSCT patients.
In double-blind, placebo-controlled trials, fluconazole reduced mucosal candidiasis and invasive Candida infections in patients undergoing HSCT. And it improved survival at day 110 after transplant.
Posaconazole prophylaxis has proven effective in patients with acute myeloid leukemia or myelodysplastic syndromes undergoing intensive chemotherapy. The drug reduced invasive fungal infections, including aspergillosis, and improved survival.
For patients with GVHD on immunosuppressive therapy, posaconazole and fluconazole prophylaxis were equivalent in preventing invasive fungal infections. However, posaconazole reduced the incidence of invasive aspergillosis and fungal-related mortality.
The NCCN guidelines, Zitella said, spell out which antifungal agents should be used for each disease or therapeutic intervention.
Antiviral prophylaxis
HSV and VZV
Patients requiring antiviral prophylaxis for herpes simplex virus (HSV) and varicella zoster virus (VZV) should be seropositive and have acute leukemia, GVHD treated with steroids, prior HSV reactivation under treatment, or have undergone HSCT.
Zitella pointed out that patients treated with proteasome inhibitors, such as bortezomib, alemtuzumab, or purine analaogs, such as fludarabine, are more at risk and should also receive antiviral prophylaxis.
Recommended drugs include valacyclovir, acyclovir, or famciclovir.
CMV
Cytomegalovirus-positive (CMV+) patients at high risk include those who have received an allogeneic HSCT or treatment with alemtuzumab.
Zitella explained that for these patients, prophylaxis is uncommon, and a pre-emptive strategy should be used, including testing 3 to 6 months after transplant or in the setting of GVHD and 2 months after alemtuzumab therapy.
CMV viremia should be treated with valganciclovir, ganciclovir, foscarnet, or cidofovir.
HBV
Zitella noted that 30% of the world population has been infected with hepatitis B virus (HBV), and reactivation during cancer treatment can lead to fulminant hepatitis and death.
NCCN recommends that patients undergoing immunosuppressive therapy, allogeneic HSCT candidates, patients receiving anti-CD20 monoclonal antibodies, those treated with alemtuzumab, and patients receiving systemic therapy who have an obvious risk factor for HBV infection should be tested.
Entecavir, tenofovir, adefovir, telbivudine, or lamivudine may be used to prevent HBV reactivation.
Pneumocystis pneumonia prophylaxis
Patients undergoing allogeneic HSCT, patients with acute lymphoblastic leukemia, those treated with alemtuzumab, and those with a CD4 count below 200 cells/mcL should receive pneumocystis pneumonia prophylaxis.
Trimethorpim/sulfamethoxazole is the drug of choice. Atovaquone, dapsone, and inhaled or IV pentamidine are alternatives.
Vaccines
Zitella pointed out that recommended vaccines include influenza, pneumococcal, and tetanus, diphtheria, and acellular pertussis.
She cautioned that live attenuated vaccines should not be given to cancer patients. Other vaccines to avoid include smallpox; measles, mumps, and rubella; varicella zoster; rotavirus; yellow fever; oral typhoid; BCG; and oral polio vaccine.
Neutropenic precautions
Low microbial diets are a hot topic among patients undergoing cancer treatment, Zitella said. Fresh fruits and vegetables used to be restricted, but no studies show that dietary restrictions decrease the risk of infection.
Zitella stressed, however, that standard food safety recommendations of the USDA/FDA should be followed.
She also noted that HEPA filtration is protective against molds in high-risk patients, antiseptic bathing has contradictory evidence, the benefit of laminar airflow is unclear, and protective isolation has not been proven to reduce the risk of infection.
Team tracks cell therapy using MRI
Scientists say they have devised a way to track the movements, destination, and persistence of a broad range of cellular therapies, without resorting to invasive procedures.
In Magnetic Resonance in Medicine, the researchers described the first human tests using a perfluorocarbon (PFC) tracer in combination with non-invasive magnetic resonance imaging (MRI) to track therapeutic immune cells injected into patients with colorectal cancer.
“Initially, we see this technique used for clinical trials that involve tests of new cell therapies,” said study author Eric T. Ahrens, PhD, of the University of California, San Diego.
“Clinical development of cell therapies can be accelerated by providing feedback regarding cell motility, optimal delivery routes, individual therapeutic doses, and engraftment success.”
Currently, there is no accepted way to image cells in the human body that covers a broad range of cell types and diseases. Earlier techniques have used metal ion-based vascular MRI contrast agents and radioisotopes.
The former have proven difficult to differentiate in vivo. The latter raise concerns about radiation toxicity and do not provide the anatomical detail available with MRIs.
“This is the first human PFC cell tracking agent, which is a new way to do MRI cell tracking,” Dr Ahrens said. “It’s the first example of a clinical MRI agent designed specifically for cell tracking.”
He and his colleagues used a PFC tracer agent and an MRI technique that directly detects fluorine atoms in labeled cells. Fluorine atoms naturally occur in extremely low concentrations in the body, making it easier to observe cells labeled with fluorine using MRI.
In this case, the modified and labeled dendritic cells were first prepared from white blood cells extracted from the patient. The cells were then injected into patients with stage 4 metastatic colorectal cancer to stimulate an anticancer T-cell immune response.
The researchers did not assess the efficacy of the cell therapy, only their ability to detect the labeled cells and monitor what happened to them. Dr Ahrens said the technique worked as expected, with the surprising finding that only half of the delivered cell vaccine remained at the inoculation site after 24 hours.
“The imaging agent technology has been shown to be able to tag any cell type that is of interest,” Dr Ahrens said. “It is a platform imaging technology for a wide range of diseases and applications.”
“Non-invasive cell tracking may help lower regulatory barriers,” he added. “For example, new stem cell therapies can be slow to obtain regulatory approvals, in part, because it is difficult, if not impossible, with current approaches to verify survival and location of transplanted cells.”
“And cell therapy trials generally have a high cost per patient. Tools that allow the investigator to gain a ‘richer’ data set from individual patients mean it may be possible to reduce patient numbers enrolled in a trial, thus reducing total trial cost.”
Scientists say they have devised a way to track the movements, destination, and persistence of a broad range of cellular therapies, without resorting to invasive procedures.
In Magnetic Resonance in Medicine, the researchers described the first human tests using a perfluorocarbon (PFC) tracer in combination with non-invasive magnetic resonance imaging (MRI) to track therapeutic immune cells injected into patients with colorectal cancer.
“Initially, we see this technique used for clinical trials that involve tests of new cell therapies,” said study author Eric T. Ahrens, PhD, of the University of California, San Diego.
“Clinical development of cell therapies can be accelerated by providing feedback regarding cell motility, optimal delivery routes, individual therapeutic doses, and engraftment success.”
Currently, there is no accepted way to image cells in the human body that covers a broad range of cell types and diseases. Earlier techniques have used metal ion-based vascular MRI contrast agents and radioisotopes.
The former have proven difficult to differentiate in vivo. The latter raise concerns about radiation toxicity and do not provide the anatomical detail available with MRIs.
“This is the first human PFC cell tracking agent, which is a new way to do MRI cell tracking,” Dr Ahrens said. “It’s the first example of a clinical MRI agent designed specifically for cell tracking.”
He and his colleagues used a PFC tracer agent and an MRI technique that directly detects fluorine atoms in labeled cells. Fluorine atoms naturally occur in extremely low concentrations in the body, making it easier to observe cells labeled with fluorine using MRI.
In this case, the modified and labeled dendritic cells were first prepared from white blood cells extracted from the patient. The cells were then injected into patients with stage 4 metastatic colorectal cancer to stimulate an anticancer T-cell immune response.
The researchers did not assess the efficacy of the cell therapy, only their ability to detect the labeled cells and monitor what happened to them. Dr Ahrens said the technique worked as expected, with the surprising finding that only half of the delivered cell vaccine remained at the inoculation site after 24 hours.
“The imaging agent technology has been shown to be able to tag any cell type that is of interest,” Dr Ahrens said. “It is a platform imaging technology for a wide range of diseases and applications.”
“Non-invasive cell tracking may help lower regulatory barriers,” he added. “For example, new stem cell therapies can be slow to obtain regulatory approvals, in part, because it is difficult, if not impossible, with current approaches to verify survival and location of transplanted cells.”
“And cell therapy trials generally have a high cost per patient. Tools that allow the investigator to gain a ‘richer’ data set from individual patients mean it may be possible to reduce patient numbers enrolled in a trial, thus reducing total trial cost.”
Scientists say they have devised a way to track the movements, destination, and persistence of a broad range of cellular therapies, without resorting to invasive procedures.
In Magnetic Resonance in Medicine, the researchers described the first human tests using a perfluorocarbon (PFC) tracer in combination with non-invasive magnetic resonance imaging (MRI) to track therapeutic immune cells injected into patients with colorectal cancer.
“Initially, we see this technique used for clinical trials that involve tests of new cell therapies,” said study author Eric T. Ahrens, PhD, of the University of California, San Diego.
“Clinical development of cell therapies can be accelerated by providing feedback regarding cell motility, optimal delivery routes, individual therapeutic doses, and engraftment success.”
Currently, there is no accepted way to image cells in the human body that covers a broad range of cell types and diseases. Earlier techniques have used metal ion-based vascular MRI contrast agents and radioisotopes.
The former have proven difficult to differentiate in vivo. The latter raise concerns about radiation toxicity and do not provide the anatomical detail available with MRIs.
“This is the first human PFC cell tracking agent, which is a new way to do MRI cell tracking,” Dr Ahrens said. “It’s the first example of a clinical MRI agent designed specifically for cell tracking.”
He and his colleagues used a PFC tracer agent and an MRI technique that directly detects fluorine atoms in labeled cells. Fluorine atoms naturally occur in extremely low concentrations in the body, making it easier to observe cells labeled with fluorine using MRI.
In this case, the modified and labeled dendritic cells were first prepared from white blood cells extracted from the patient. The cells were then injected into patients with stage 4 metastatic colorectal cancer to stimulate an anticancer T-cell immune response.
The researchers did not assess the efficacy of the cell therapy, only their ability to detect the labeled cells and monitor what happened to them. Dr Ahrens said the technique worked as expected, with the surprising finding that only half of the delivered cell vaccine remained at the inoculation site after 24 hours.
“The imaging agent technology has been shown to be able to tag any cell type that is of interest,” Dr Ahrens said. “It is a platform imaging technology for a wide range of diseases and applications.”
“Non-invasive cell tracking may help lower regulatory barriers,” he added. “For example, new stem cell therapies can be slow to obtain regulatory approvals, in part, because it is difficult, if not impossible, with current approaches to verify survival and location of transplanted cells.”
“And cell therapy trials generally have a high cost per patient. Tools that allow the investigator to gain a ‘richer’ data set from individual patients mean it may be possible to reduce patient numbers enrolled in a trial, thus reducing total trial cost.”
Blood testing system wins marketing authorization in US
Credit: Juan D. Alfonso
The US Food and Drug Administration (FDA) has granted marketing authorization for the T2Candida® Panel and the T2Dx® Instrument, a system that provides direct detection of 5 yeast pathogens in whole blood samples.
The system can detect Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata, and Candida krusei in patients with symptoms of, or medical conditions predisposing them to, invasive fungal infections.
It can take up to 6 days to detect yeast pathogens using blood culture, and even more time to identify the specific type of yeast present.
The T2Candida system can identify specific Candida pathogens from a single blood sample within 3 to 5 hours.
However, false positive results are possible with this system, so physicians should perform blood cultures to confirm T2Candida results, according to the FDA. Still, a negative test result may provide timely data that allows physicians to avoid or suspend unnecessary antifungal treatment.
“By testing 1 blood sample for 5 yeast pathogens—and getting results within a few hours—physicians can initiate appropriate antifungal treatment earlier and potentially reduce patient illness and decrease the risk of dying from these infections,” said Alberto Gutierrez, director of the Office of In Vitro Diagnostics and Radiological Health at the FDA’s Center for Devices and Radiological Health.
How the system works
The T2Candida panel and T2Dx instrument are powered by T2MR, a miniaturized, magnetic-resonance-based diagnostic approach that measures how water molecules react in the presence of magnetic fields.
The system uses blood-compatible polymerase chain reaction to amplify Candida DNA, which then binds to superparamagnetic nanoparticles coated with a complementary DNA strand. The binding event causes the nanoparticles to cluster, which changes the sample’s T2 magnetic resonance signal.
If the system detects yeast DNA, it can then determine the species category to which the DNA belongs, which helps point healthcare providers to the appropriate treatment.
T2Dx is a fully automated, bench-top instrument. To perform a test, the patient sample is snapped onto a disposable test cartridge, which is preloaded with the necessary reagents. The cartridge is then inserted into T2Dx, which processes the sample and delivers a diagnostic test result.
Studies and FDA review
The FDA reviewed the T2Candida panel and the T2Dx instrument through the agency’s de novo classification process, a regulatory pathway for certain novel, low- to moderate-risk medical devices.
The FDA based its review on a clinical study of 1500 patients, in which the T2Candida system correctly categorized nearly 100% of the negative specimens as negative for the presence of yeast.
In a separate study of 300 blood samples with specific concentrations of yeast, the system correctly identified the organism in 84% to 96% of the positive specimens.
The T2Candida panel and T2Dx instrument are manufactured by T2 Biosystems, Inc.
Credit: Juan D. Alfonso
The US Food and Drug Administration (FDA) has granted marketing authorization for the T2Candida® Panel and the T2Dx® Instrument, a system that provides direct detection of 5 yeast pathogens in whole blood samples.
The system can detect Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata, and Candida krusei in patients with symptoms of, or medical conditions predisposing them to, invasive fungal infections.
It can take up to 6 days to detect yeast pathogens using blood culture, and even more time to identify the specific type of yeast present.
The T2Candida system can identify specific Candida pathogens from a single blood sample within 3 to 5 hours.
However, false positive results are possible with this system, so physicians should perform blood cultures to confirm T2Candida results, according to the FDA. Still, a negative test result may provide timely data that allows physicians to avoid or suspend unnecessary antifungal treatment.
“By testing 1 blood sample for 5 yeast pathogens—and getting results within a few hours—physicians can initiate appropriate antifungal treatment earlier and potentially reduce patient illness and decrease the risk of dying from these infections,” said Alberto Gutierrez, director of the Office of In Vitro Diagnostics and Radiological Health at the FDA’s Center for Devices and Radiological Health.
How the system works
The T2Candida panel and T2Dx instrument are powered by T2MR, a miniaturized, magnetic-resonance-based diagnostic approach that measures how water molecules react in the presence of magnetic fields.
The system uses blood-compatible polymerase chain reaction to amplify Candida DNA, which then binds to superparamagnetic nanoparticles coated with a complementary DNA strand. The binding event causes the nanoparticles to cluster, which changes the sample’s T2 magnetic resonance signal.
If the system detects yeast DNA, it can then determine the species category to which the DNA belongs, which helps point healthcare providers to the appropriate treatment.
T2Dx is a fully automated, bench-top instrument. To perform a test, the patient sample is snapped onto a disposable test cartridge, which is preloaded with the necessary reagents. The cartridge is then inserted into T2Dx, which processes the sample and delivers a diagnostic test result.
Studies and FDA review
The FDA reviewed the T2Candida panel and the T2Dx instrument through the agency’s de novo classification process, a regulatory pathway for certain novel, low- to moderate-risk medical devices.
The FDA based its review on a clinical study of 1500 patients, in which the T2Candida system correctly categorized nearly 100% of the negative specimens as negative for the presence of yeast.
In a separate study of 300 blood samples with specific concentrations of yeast, the system correctly identified the organism in 84% to 96% of the positive specimens.
The T2Candida panel and T2Dx instrument are manufactured by T2 Biosystems, Inc.
Credit: Juan D. Alfonso
The US Food and Drug Administration (FDA) has granted marketing authorization for the T2Candida® Panel and the T2Dx® Instrument, a system that provides direct detection of 5 yeast pathogens in whole blood samples.
The system can detect Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata, and Candida krusei in patients with symptoms of, or medical conditions predisposing them to, invasive fungal infections.
It can take up to 6 days to detect yeast pathogens using blood culture, and even more time to identify the specific type of yeast present.
The T2Candida system can identify specific Candida pathogens from a single blood sample within 3 to 5 hours.
However, false positive results are possible with this system, so physicians should perform blood cultures to confirm T2Candida results, according to the FDA. Still, a negative test result may provide timely data that allows physicians to avoid or suspend unnecessary antifungal treatment.
“By testing 1 blood sample for 5 yeast pathogens—and getting results within a few hours—physicians can initiate appropriate antifungal treatment earlier and potentially reduce patient illness and decrease the risk of dying from these infections,” said Alberto Gutierrez, director of the Office of In Vitro Diagnostics and Radiological Health at the FDA’s Center for Devices and Radiological Health.
How the system works
The T2Candida panel and T2Dx instrument are powered by T2MR, a miniaturized, magnetic-resonance-based diagnostic approach that measures how water molecules react in the presence of magnetic fields.
The system uses blood-compatible polymerase chain reaction to amplify Candida DNA, which then binds to superparamagnetic nanoparticles coated with a complementary DNA strand. The binding event causes the nanoparticles to cluster, which changes the sample’s T2 magnetic resonance signal.
If the system detects yeast DNA, it can then determine the species category to which the DNA belongs, which helps point healthcare providers to the appropriate treatment.
T2Dx is a fully automated, bench-top instrument. To perform a test, the patient sample is snapped onto a disposable test cartridge, which is preloaded with the necessary reagents. The cartridge is then inserted into T2Dx, which processes the sample and delivers a diagnostic test result.
Studies and FDA review
The FDA reviewed the T2Candida panel and the T2Dx instrument through the agency’s de novo classification process, a regulatory pathway for certain novel, low- to moderate-risk medical devices.
The FDA based its review on a clinical study of 1500 patients, in which the T2Candida system correctly categorized nearly 100% of the negative specimens as negative for the presence of yeast.
In a separate study of 300 blood samples with specific concentrations of yeast, the system correctly identified the organism in 84% to 96% of the positive specimens.
The T2Candida panel and T2Dx instrument are manufactured by T2 Biosystems, Inc.
Library can help cut cost of syringe pumps
Credit: Darren Baker
Researchers have published an open-source library of designs that could allow scientists to cut the cost of syringe pumps.
These syringe-pump designs can be made on a RepRap 3D printer for the cost of the plastic filament, and the designs are customizable.
“Not only have we designed a single syringe pump, we’ve designed all future syringe pumps,” said Joshua Pearce, PhD, of Michigan Technological University in Houghton.
“Scientists can customize the design of a pump for exactly what they are doing, just by changing a couple of numbers in the software.”
Dr Pearce and his colleagues described their work creating the library of designs in PLOS ONE. The hardware plans, designs, and source code for the pumps are available on Appropedia.
The library includes recipes for most parts of a syringe pump. Scientists will have to buy the small electric stepper motor that drives the liquid, some simple hardware, and the syringe itself.
The researchers also incorporated a low-cost, credit card-sized Raspberry Pi computer as a wireless controller.
“That way, you can link the syringe pump to the network, sit on a beach in Hawaii, and control your lab,” Dr Pearce said. “Plenty of people can have access, and you can run multiple experiments at the same time. Our entire single-pump system costs only $50 and can replace pumps that run between $250 and $2500.”
It costs more to make a double-pump system, about $120, but it replaces a commercial system that costs $5000.
And Dr Pearce believes someone will find a way to make the pumps even better.
“I’m sure someone will improve our designs and share their results with us and the rest of the community,” he said. “That’s the beauty and power of open source.”
Credit: Darren Baker
Researchers have published an open-source library of designs that could allow scientists to cut the cost of syringe pumps.
These syringe-pump designs can be made on a RepRap 3D printer for the cost of the plastic filament, and the designs are customizable.
“Not only have we designed a single syringe pump, we’ve designed all future syringe pumps,” said Joshua Pearce, PhD, of Michigan Technological University in Houghton.
“Scientists can customize the design of a pump for exactly what they are doing, just by changing a couple of numbers in the software.”
Dr Pearce and his colleagues described their work creating the library of designs in PLOS ONE. The hardware plans, designs, and source code for the pumps are available on Appropedia.
The library includes recipes for most parts of a syringe pump. Scientists will have to buy the small electric stepper motor that drives the liquid, some simple hardware, and the syringe itself.
The researchers also incorporated a low-cost, credit card-sized Raspberry Pi computer as a wireless controller.
“That way, you can link the syringe pump to the network, sit on a beach in Hawaii, and control your lab,” Dr Pearce said. “Plenty of people can have access, and you can run multiple experiments at the same time. Our entire single-pump system costs only $50 and can replace pumps that run between $250 and $2500.”
It costs more to make a double-pump system, about $120, but it replaces a commercial system that costs $5000.
And Dr Pearce believes someone will find a way to make the pumps even better.
“I’m sure someone will improve our designs and share their results with us and the rest of the community,” he said. “That’s the beauty and power of open source.”
Credit: Darren Baker
Researchers have published an open-source library of designs that could allow scientists to cut the cost of syringe pumps.
These syringe-pump designs can be made on a RepRap 3D printer for the cost of the plastic filament, and the designs are customizable.
“Not only have we designed a single syringe pump, we’ve designed all future syringe pumps,” said Joshua Pearce, PhD, of Michigan Technological University in Houghton.
“Scientists can customize the design of a pump for exactly what they are doing, just by changing a couple of numbers in the software.”
Dr Pearce and his colleagues described their work creating the library of designs in PLOS ONE. The hardware plans, designs, and source code for the pumps are available on Appropedia.
The library includes recipes for most parts of a syringe pump. Scientists will have to buy the small electric stepper motor that drives the liquid, some simple hardware, and the syringe itself.
The researchers also incorporated a low-cost, credit card-sized Raspberry Pi computer as a wireless controller.
“That way, you can link the syringe pump to the network, sit on a beach in Hawaii, and control your lab,” Dr Pearce said. “Plenty of people can have access, and you can run multiple experiments at the same time. Our entire single-pump system costs only $50 and can replace pumps that run between $250 and $2500.”
It costs more to make a double-pump system, about $120, but it replaces a commercial system that costs $5000.
And Dr Pearce believes someone will find a way to make the pumps even better.
“I’m sure someone will improve our designs and share their results with us and the rest of the community,” he said. “That’s the beauty and power of open source.”