Incidence and predictors of delayed congestive heart failure (CHF) after hematologic malignancies treated with autologous hematopoietic cell transplantation (aHCT).

Abstract

9042 Background: aHCT survivors are at risk for CHF due to exposure to cardiotoxic agents (pre-aHCT anthracyclines, chest radiation, aHCT conditioning). The magnitude of risk of CHF and risk factors are not defined, nor is the modifying effect of preventable causes, such as cardiovascular risk factors (CV RF). Methods: A retrospective cohort design was used to describe the cumulative incidence (CI) of CHF and examine the role of aHCT conditioning and sociodemographic factors. Next, a nested case-control approach was used to evaluate the role of pre-aHCT exposures and post-aHCT CV RF. Results: Eighty-one cases of CHF were observed in a cohort of 1,010 aHCT survivors transplanted at City of Hope between 1988 and 2002, followed for a median of 6.7 yrs (1-21). Median age at aHCT was 44.4 yrs (17-69); median time to CHF: 3.0 yrs (0.02-18.6); 40% were females; 71% non-Hispanic white; 68% underwent aHCT for lymphoma. CI of CHF was 7.8% at 10 yrs and 10.4% at 15 yrs post-aHCT. Female gender (Hazard Ratio [HR] 2.5, p<0.01), diagnosis of Hodgkin lymphoma (HR 2.9, p=0.02), and older age at aHCT (35-44 yrs: HR 2.2, p=0.03; 45-54 yrs: HR 2.9, p<0.01; ≥55 yrs: HR 4.5, p<0.01; referent group <35 yrs) were independent predictors of CHF. Risk was highest for female lymphoma survivors: CI of 17.5% at 15 yrs. Conditioning-related exposures were not associated with CHF risk. A clear interaction between cumulative anthracycline exposure ≥250 mg/m2 and post-aHCT CV RF (hypertension and diabetes) were identified (Table). Overall survival was 28% at 5 yrs after diagnosis of CHF. Conclusions: Cumulative incidence of CHF exceeds 10% at 15 years after aHCT. Female lymphoma survivors constitute a vulnerable population. Post-aHCT diabetes and hypertension interact with high-dose anthracycline exposure to significantly increase risk. These data form the basis for targeted surveillance and aggressive management of comorbidities. Hypertension Diabetes Dyslipidemia OR P OR P OR P No CV RF, no HD anthracycline 1.0 1.0 1.0 CV RF, no HD anthracycline 2.9 0.14 4.1 0.13 3.2 0.16 No CV RF, HD anthracycline 3.7 <0.01 3.8 <0.01 4.7 <0.01 CV RF + HD anthracycline 27.4 <0.01 21.5 <0.01 4.0 0.03 Abbreviation: HD, high dose.