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STUDY SUGGESTS STEM CELL TRANSPLANT SURVIVORS AT INCREASED RISK OF DEVELOPING HEART DISEASE
e! Science News
Oct 3 2012
Published: Wednesday, October 3, 2012 - 14:37 in Health & Medicine
New research appearing online October 3 in Blood, the Journal of
the American Society of Hematology (ASH), suggests that long-term
survivors of hematopoietic cell transplants (HCT) are at an increased
risk of developing heart disease risk factors such as high blood
pressure, diabetes, and high cholesterol when compared to the general
population. These risk factors, combined with exposure to pre-HCT
therapy, contribute to a noticeably increased risk of heart disease
over time. HCT, the transplantation of blood-forming stem cells from
the bone marrow, circulating blood, or umbilical cord blood, is the
primary treatment option for many patients with blood disorders. The
healthy transplanted stem cells replace patients' damaged cells that
caused their illness. Advances in transplantation strategies have
contributed to marked improvements in patient outcomes, resulting
in a growing number of long-term transplant survivors, many of whom
struggle with one or more chronic, post-transplant health conditions.
Previous researchers have speculated that survivors' exposure to
potentially heart damaging pre-transplant chemotherapy and radiation
or treatment for a life-threatening transplant complication known as
graft-versus-host-disease (GVHD) can increase their risk of developing
heart disease and its associated risk factors. However, there have
been limited data to validate the contribution of pre-conditioning
chemotherapy or radiation and GVHD to the eventual development of
heart disease in long-term HCT survivors.
"While we know that heart disease is a real concern for long-term
HCT survivors, small sample sizes and a lack of long-term follow up
in previous studies have only allowed us to look at a small piece of
the puzzle of how this chronic condition develops in these patients,"
said Saro H. Armenian, DO, MPH, the study's first author, Assistant
Professor in the Division of Outcomes Research, and Medical Director of
the Pediatric Survivorship Clinic in the Childhood Cancer Survivorship
Program at City of Hope in Duarte, CA. "Our study sought to better
determine the specific factors before and after transplant that can
lead to heart disease in a large group of transplant recipients."
In order to more thoroughly evaluate heart disease risk and development
in HCT recipients, Dr. Armenian and his team of researchers designed
a retrospective study to evaluate factors that may affect a survivor's
risk of developing high blood pressure, diabetes, and high cholesterol
after HCT. These factors included transplant recipients' exposure to
pre-transplant chemotherapy and radiation, conditioning therapy for
HCT, their type of HCT transplant, and whether they developed and
were treated for GVHD post transplant.
To better determine HCT survivors' incidence of high blood pressure,
diabetes, and high cholesterol compared to the general population,
researchers analyzed medical records of 1,885 patients who underwent
a first-time HCT for a blood cancer at City of Hope between 1995
and 2004 and had survived at least one year. The National Health
and Nutrition Examination Survey was used to generate expected heart
disease risk factor rates for the general population.
Following their analysis, researchers found a higher prevalence of
high blood pressure, diabetes, and high cholesterol in long-term HCT
transplant survivors when compared to the general population. HCT
conditioning with total body radiation was associated with a 1.5-fold
increase in risk of developing diabetes and a 1.4-fold increase
in risk of developing high cholesterol, regardless of HCT type, a
finding that validates previous reports from long-term childhood and
adult HCT survivors. While the mechanism by which total body radiation
increases the risk of diabetes and high cholesterol in HCT recipients
is not clear, previous studies have shown that abdominal radiation
may contribute to known heart disease risk factors such as insulin
resistance and an increase in belly fat in conventionally treated
cancer patients. This evidence suggests that radiation-induced
pancreatic or liver injury may play a role in an HCT transplant
survivor's development of heart disease by increasing their risk for
heart disease risk factors.
Next, researchers assessed the role of transplant type on long-term
HCT survivors' risk of developing key heart disease risk factors.
After reviewing the data, researchers observed that those who had
received transplanted stem cells from a donor (allogeneic HCT) were
at a significantly higher risk of developing high blood pressure,
diabetes, or high cholesterol after transplant than those who had
received blood-forming stem cells from their own body (autologous
HCT). Over the 10-year study period, 45.3 percent of allogeneic
HCT recipients developed high blood pressure, 20.9 percent developed
diabetes, and 50.5 percent developed high cholesterol; whereas only 32
percent, 15.9 percent, and 43.3 percent of autologous HCT recipients
developed these same conditions, respectively. Transplant recipients
who had undergone an allogeneic HCT and who had experienced GVHD had
the highest risk of developing heart disease risk factors, researchers
concluded; 54.7 percent of this group developed high blood pressure,
25.8 percent developed diabetes, and 52.8 percent developed high
cholesterol.
Not only did more allogeneic than autologous HCT recipients develop
these heart disease risk factors over this time period, but they also
developed them more quickly. Allogeneic HCT recipients developed high
blood pressure and high cholesterol both at a median time to onset of
2.5 months, compared with autologous HCT recipients who developed the
same conditions at 3.7 years and 1.6 years, respectively. Allogeneic
HCT recipients also developed diabetes more than two years earlier than
autologous recipients (1.2 year median time to onset for allogeneic
HCT recipients vs. 3.3 years for autologous transplant recipients).
In addition to evaluating incidence rates of key heart disease risk
factors in this large group of long-term HCT survivors, investigators
also assessed their impact on survivors' subsequent development
of heart disease. A total of 115 patients went on to develop heart
disease at a median rate of four years after HCT. At 10 years post HCT,
the cumulative incidence of post-HCT heart disease in all survivors
was approximately 7.8 percent, with the rate exceeding 11 percent
in the survivors with multiple heart disease risk factors. In those
survivors with multiple heart disease risk factors and past exposure
to cardiotoxic chemotherapy or radiation, the incidence rose to
approximately 18 percent, demonstrating that certain pre-transplant
therapeutic exposures compound HCT recipients' risk of developing
heart disease.
"Our findings show that the process of receiving a stem cell
transplant alone increases a recipient's risk of developing heart
disease; however, the type of transplant and whether the recipient was
treated for GVHD can also increase that survivor's heart disease risk
as well," said Dr. Armenian. "The results of this study demonstrate
the importance of intervention strategies that can help mitigate
these modifiable heart disease risk factors in transplant recipients
before and after transplant, and we hope they can serve as a basis
for creating a predictive model to identify those patients at highest
risk of developing heart disease."
Source: American Society of Hematology
http://esciencenews.com/articles/2012/10/03/study.suggests.stem.cell.transplant.survivors.incr eased.risk.developing.heart.disease
e! Science News
Oct 3 2012
Published: Wednesday, October 3, 2012 - 14:37 in Health & Medicine
New research appearing online October 3 in Blood, the Journal of
the American Society of Hematology (ASH), suggests that long-term
survivors of hematopoietic cell transplants (HCT) are at an increased
risk of developing heart disease risk factors such as high blood
pressure, diabetes, and high cholesterol when compared to the general
population. These risk factors, combined with exposure to pre-HCT
therapy, contribute to a noticeably increased risk of heart disease
over time. HCT, the transplantation of blood-forming stem cells from
the bone marrow, circulating blood, or umbilical cord blood, is the
primary treatment option for many patients with blood disorders. The
healthy transplanted stem cells replace patients' damaged cells that
caused their illness. Advances in transplantation strategies have
contributed to marked improvements in patient outcomes, resulting
in a growing number of long-term transplant survivors, many of whom
struggle with one or more chronic, post-transplant health conditions.
Previous researchers have speculated that survivors' exposure to
potentially heart damaging pre-transplant chemotherapy and radiation
or treatment for a life-threatening transplant complication known as
graft-versus-host-disease (GVHD) can increase their risk of developing
heart disease and its associated risk factors. However, there have
been limited data to validate the contribution of pre-conditioning
chemotherapy or radiation and GVHD to the eventual development of
heart disease in long-term HCT survivors.
"While we know that heart disease is a real concern for long-term
HCT survivors, small sample sizes and a lack of long-term follow up
in previous studies have only allowed us to look at a small piece of
the puzzle of how this chronic condition develops in these patients,"
said Saro H. Armenian, DO, MPH, the study's first author, Assistant
Professor in the Division of Outcomes Research, and Medical Director of
the Pediatric Survivorship Clinic in the Childhood Cancer Survivorship
Program at City of Hope in Duarte, CA. "Our study sought to better
determine the specific factors before and after transplant that can
lead to heart disease in a large group of transplant recipients."
In order to more thoroughly evaluate heart disease risk and development
in HCT recipients, Dr. Armenian and his team of researchers designed
a retrospective study to evaluate factors that may affect a survivor's
risk of developing high blood pressure, diabetes, and high cholesterol
after HCT. These factors included transplant recipients' exposure to
pre-transplant chemotherapy and radiation, conditioning therapy for
HCT, their type of HCT transplant, and whether they developed and
were treated for GVHD post transplant.
To better determine HCT survivors' incidence of high blood pressure,
diabetes, and high cholesterol compared to the general population,
researchers analyzed medical records of 1,885 patients who underwent
a first-time HCT for a blood cancer at City of Hope between 1995
and 2004 and had survived at least one year. The National Health
and Nutrition Examination Survey was used to generate expected heart
disease risk factor rates for the general population.
Following their analysis, researchers found a higher prevalence of
high blood pressure, diabetes, and high cholesterol in long-term HCT
transplant survivors when compared to the general population. HCT
conditioning with total body radiation was associated with a 1.5-fold
increase in risk of developing diabetes and a 1.4-fold increase
in risk of developing high cholesterol, regardless of HCT type, a
finding that validates previous reports from long-term childhood and
adult HCT survivors. While the mechanism by which total body radiation
increases the risk of diabetes and high cholesterol in HCT recipients
is not clear, previous studies have shown that abdominal radiation
may contribute to known heart disease risk factors such as insulin
resistance and an increase in belly fat in conventionally treated
cancer patients. This evidence suggests that radiation-induced
pancreatic or liver injury may play a role in an HCT transplant
survivor's development of heart disease by increasing their risk for
heart disease risk factors.
Next, researchers assessed the role of transplant type on long-term
HCT survivors' risk of developing key heart disease risk factors.
After reviewing the data, researchers observed that those who had
received transplanted stem cells from a donor (allogeneic HCT) were
at a significantly higher risk of developing high blood pressure,
diabetes, or high cholesterol after transplant than those who had
received blood-forming stem cells from their own body (autologous
HCT). Over the 10-year study period, 45.3 percent of allogeneic
HCT recipients developed high blood pressure, 20.9 percent developed
diabetes, and 50.5 percent developed high cholesterol; whereas only 32
percent, 15.9 percent, and 43.3 percent of autologous HCT recipients
developed these same conditions, respectively. Transplant recipients
who had undergone an allogeneic HCT and who had experienced GVHD had
the highest risk of developing heart disease risk factors, researchers
concluded; 54.7 percent of this group developed high blood pressure,
25.8 percent developed diabetes, and 52.8 percent developed high
cholesterol.
Not only did more allogeneic than autologous HCT recipients develop
these heart disease risk factors over this time period, but they also
developed them more quickly. Allogeneic HCT recipients developed high
blood pressure and high cholesterol both at a median time to onset of
2.5 months, compared with autologous HCT recipients who developed the
same conditions at 3.7 years and 1.6 years, respectively. Allogeneic
HCT recipients also developed diabetes more than two years earlier than
autologous recipients (1.2 year median time to onset for allogeneic
HCT recipients vs. 3.3 years for autologous transplant recipients).
In addition to evaluating incidence rates of key heart disease risk
factors in this large group of long-term HCT survivors, investigators
also assessed their impact on survivors' subsequent development
of heart disease. A total of 115 patients went on to develop heart
disease at a median rate of four years after HCT. At 10 years post HCT,
the cumulative incidence of post-HCT heart disease in all survivors
was approximately 7.8 percent, with the rate exceeding 11 percent
in the survivors with multiple heart disease risk factors. In those
survivors with multiple heart disease risk factors and past exposure
to cardiotoxic chemotherapy or radiation, the incidence rose to
approximately 18 percent, demonstrating that certain pre-transplant
therapeutic exposures compound HCT recipients' risk of developing
heart disease.
"Our findings show that the process of receiving a stem cell
transplant alone increases a recipient's risk of developing heart
disease; however, the type of transplant and whether the recipient was
treated for GVHD can also increase that survivor's heart disease risk
as well," said Dr. Armenian. "The results of this study demonstrate
the importance of intervention strategies that can help mitigate
these modifiable heart disease risk factors in transplant recipients
before and after transplant, and we hope they can serve as a basis
for creating a predictive model to identify those patients at highest
risk of developing heart disease."
Source: American Society of Hematology
http://esciencenews.com/articles/2012/10/03/study.suggests.stem.cell.transplant.survivors.incr eased.risk.developing.heart.disease