Population-Based Analysis of Late Cardiovascular Morbidity and Hospitalizations After Hematopoietic Cell Transplantation.

There is growing evidence that recipients of hematopoietic cell transplantation (HCT) have increased risk of adverse long-term effects such as hypertension, dyslipidemia, and diabetes which may contribute to increased cardiovascular (CV) morbidity and mortality.

The Fred Hutchinson Cancer Research Center (FHCRC) performs the vast majority of HCTs in Washington State. We linked the medical records of all 2-year HCT survivors who were state residents treated at FHCRC from 1985-2005 (n=1405; 62% allogeneic; 38% autologous) to the state's hospital discharge and death registries beginning 2 years after HCT. Individuals randomly selected from state driver's license files (n=5964) served as a comparison group, frequency-matched by age, sex, and county of residence. Selected serious CV diagnoses (ischemic heart disease, dysrhythmia, cardiomyopathy/heart failure, stroke and other vascular disease) and related diseases (dyslipidemia, diabetes, chronic renal disease) were identified from these databases for the HCT and comparison cohorts. Odds ratio (OR) estimates of the relative risk were calculated using logistic regression adjusted for age and year of HCT/driver's license filing, sex, and race/ethnicity (HCT patients only).

With a median age at HCT of 40 (0-73) years and follow-up time of 5 (2-22) years since HCT, survivors were significantly more likely to have subsequent CV and related diagnoses recorded in hospital discharge (28% vs. 10%; p<0.01) and death records (4% vs. 1%; p<0.01) vs. the comparison group. In particular, dysrhythmia, cardiomyopathy/heart failure, stroke and other vascular diseases, diabetes, and chronic renal disease were recorded more frequently among the HCT cohort. Rates of ischemic heart disease were not significantly different between the 2 groups (4% vs. 3%; p=0.14). In multivariable analyses, factors independently associated with increased CV hospitalizations included history of chronic graft vs. host disease (OR 2.0 [1.4-2.7]) and receiving >1 HCT of any type (OR 2.1 [1.4-3.0]). Receiving >1 HCT also was associated with statistically significant 2-3 fold increased risks of dysrhythmia, cardiomyopathy/heart failure, and chronic renal disease. Allogeneic transplants and preparative regimens containing total body irradiation (TBI) were not associated with an increased risk of CV hospitalization compared with autologous transplants and non-TBI containing regimens, respectively. While older age at baseline was associated with an increased risk of most CV outcomes in both groups, in age-stratified analysis, those who received HCT at a younger age had the greatest risk vs. similar-aged comparison subjects (e.g. <20 years at HCT, CV hospitalization OR=37.8 [16.5-86.2]; ≥60 years at HCT, OR=1.7 [1.1-2.6]). In contrast to the comparison group, among HCT survivors increased body mass index was not consistently associated with an increased risk of CV outcomes except for diabetes.

CV-related hospitalizations and deaths occurred significantly more often among 2-year HCT survivors than the comparison group, as measured by hospital discharge and death registries. Similar risk was observed following allogeneic and autologous transplants. Patients who received HCT at a younger age and those who experienced multiple transplants of any type were at particularly increased risk. To more completely delineate risk factors, future analyses will examine the effects of pre-HCT anthracycline and chest radiotherapy exposures, and elapsed time since HCT.

No relevant conflicts of interest to declare.