Long-term survivors of blood-related cancers who had stem cell transplants are at risk of developing risk factors that can lead to heart disease, researchers found.
Overall, the presence of hypertension, diabetes, and dyslipidemia was significantly higher among hematopoietic cell transplant (HCT) recipients compared with the general population, according to Saro H. Armenian, DO, MPH, of City of Hope in Duarte, Calif., and colleagues.
Importantly, those who received hematopoietic cells from a donor had a greater risk of developing these cardiovascular risk factors compared with autologous cells transplant recipients, researchers reported online in Blood: Journal of the American Society of Hematology.
The authors pointed to two factors that could increase the cardiovascular risk in these patients:
- Pre-transplant chemotherapy and radiation
- Treatment for the transplant complication of graft-versus-host disease (GVHD)
Donor cell recipients generally undergo higher doses of chemotherapy plus total body radiation to condition the body for the foreign cells.
Patients who received allogeneic HCT developed hypertension, diabetes, and dyslipidemia in significantly shorter periods compared to autologous HCT:
- Hypertension -- 0.2 versus 3.7 years (P<0.01)
- Diabetes -- 1.2 versus 3.3 years (P<0.01)
- Dyslipidemia -- 0.2 versus 1.6 years (P<0.01)
Researchers also found a linear relationship with the number of risk factors and the development of cardiovascular disease, which included heart failure, coronary artery disease, myocardial infarction, and stroke.
A total of 115 patients out of the cohort of 1,885 developed cardiovascular disease: 4.7% had no risk factors, 7% had one, and 11.2% had two or more at 10 years. The trend was significant atP<0.01.
Armenian and colleagues noted that advances in blood-forming stem cell strategies allow recipients to live longer, but they often have one or more chronic, post-transplant health conditions.
They pointed to a study that found the cumulative incidence of severe or life-threatening conditions to be 40% at 15 years after HCT.
But studies examining factors related to cardiovascular risk in these patients have been limited by small size, short follow-up, lack of comparisons between autologous and allogeneic donors, and lack of age and gender comparisons, the investigators said.
"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," Armenian said in a statement.
Researchers retrospectively analyzed medical records of 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 median age was 44, women comprised 57% of the cohort, and 63% were white. The median follow-up after HCT was 6 years.
Patients were being treated for Hodgkin or non-Hodgkin lymphoma (38.6%), acute lymphoblastic or myeloid leukemia (25.6%), multiple myeloma (15.3%), chronic leukemia (12.8%), or other type of blood cancer (7.7%).
Treatment-related exposures included pre-HCT anthracycline chemotherapy and chest radiation, as well as high-dose chemotherapy and radiation related to the conditioning regimen. Patients being treated for GVHD generally received corticosteroids and cyclosporine and sometimes mycophenolate mofetil, tacrolimus, or sirolimus.
To be included, patients had to have clinically validated hypertension, diabetes, or dyslipidemia for a minimum of 6 months and the condition had to persist for more than a year after HCT.
The cumulative incidence of the cardiovascular risk factors at 10 years after HCT was:
- Hypertension -- 37%
- Diabetes -- 18%
- Dyslipidemia -- 47%
When Armenian and colleagues performed a multivariate analysis, significant predictors of developing all three cardiovascular risk factors were older age (both 35-55 and a higher risk for age >55) and obesity (≥30 kg/m2).
Patients who had chemotherapy plus total body radiation had a 1.5-fold increased risk of diabetes and a 1.4-fold increased risk of high cholesterol, regardless of HCT type.
And allogeneic HCT without acute GVHD carried a 5.2-fold higher risk for hypertension, 2.6-fold higher risk for diabetes, and a 2.2-fold higher risk for dyslipidemia.
The risk increased when the allogeneic recipients had grade II, III, or IV acute GVHD (HRs 9.1, 5.8, and 3.2, respectively).
The study was limited by its retrospective nature and lack of access to information about gonadal dysfunction, smoking history, family history, and physical activity history, the authors noted.
They also did not have access to lifetime doses of immunosuppressive therapy, and the study did not include those who underwent T-cell-depleted HCT.
The study was funding by the National Institutes of Health and the Lymphoma/Leukemia Society Scholar Award for Clinical Research.
The authors reported they have no relevant financial conflicts of interest to disclose.
From the American Heart Association:
Primary source: Blood: Journal of the American Society of Hematology
Source reference:
Armenian SH, et al "Cardiovascular risk factors in hematopoietic cell transplantation (HCT) survivors: role in development of subsequent cardiovascular disease" Blood 2012; DOI: 10.1182/blood-2012-06-437178.
Source reference:
Armenian SH, et al "Cardiovascular risk factors in hematopoietic cell transplantation (HCT) survivors: role in development of subsequent cardiovascular disease" Blood 2012; DOI: 10.1182/blood-2012-06-437178.
Chris Kaiser
Cardiology Editor
Chris has written and edited for medical publications for more than 15 years. As the news editor for aUnited Business Media journal, he was awarded Best News Section. He has a B.A. from La Salle University and an M.A. from Villanova University. Chris is based outside of Philadelphia and is also involved with the theater as a writer, director, and occasional actor.
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