Work

Risk Factors for Late Cardiovascular Morbidity and Mortality After Hematopoietic Cell Transplantation

Year: 2011

Type: article

Abstract: To examine the effect of pre-transplant treatment and transplant related-risk factors for late cardiovascular (CV) disease following hematopoietic cell transplantation (HCT). Nested case-cohort study. All 2 yr HCT survivors who were Washington State residents treated at the Fred Hutchinson Cancer Research Center from 1985-2006 (n = 1491; 56% allogeneic, 44% autologous) were linked to the state's hospital discharge and death registries beginning 2 yrs after HCT (1987-2008). Deaths and hospitalizations due to selected CV diagnoses (ischemic heart disease, cardiomyopathy, dysrhythmia, stroke and other vascular disease) and related conditions (hypertension, dyslipidemia, diabetes, renal disease/dialysis) were identified. Relationships (hazard ratios, HR) among treatment risk factors and CV outcomes were examined between affected survivors (cases, n = 436) and a randomly selected subset of the remaining HCT cohort (n = 371). Among these 807 survivors, median age at HCT was 41 (0-73) yrs and time to event was 5 (2-24) yrs. Individual CV events included: 39 CV-related deaths, 56 ischemic heart disease, 80 cardiomyopathy, 109 dysrhythmia, 33 stroke, and 52 other vascular disease. In multivariable models, survivors with cumulative anthracycline exposures ≥ 300 mg/m2 were more likely to experience CV death (HR 2.8, 95% CI 1.0-7.6), cardiomyopathy (HR 2.1, 95% CI 1.0-4.4), and dysrhythmia (HR 1.9, 95% CI 1.1-3.3). The association between anthracycline dose and CV outcomes appeared greater following allogeneic than autologous HCT. Allogeneic HCT also was associated with increased risk of hypertension (HR 1.6, 95% CI 1.1-2.3), with unrelated donor HCT and chronic graft versus host disease (GVHD) being significant risk factors. Total body irradiation and chest radiation were not independently associated with any CV outcome. In sub-analyses, survivors with dyslipidemia 1 yr after HCT had an increased risk of subsequent ischemic heart disease (HR 8.9, 95% CI 3.1-25.9), and those with both dyslipidemia and hypertension 1 yr after HCT also had increased risk of subsequent diabetes (HR 4.3, 95% CI 1.6-11.2). Increased exposure to pre-HCT anthracyclines was associated with multiple adverse CV outcomes after HCT, including CV death. HCT with unrelated donors and chronic GVHD were associated with increased risk of hypertension, but other HCT-specific exposures were not consistently associated with additional risk of CV morbidity.Table 1Risk of Selected Cardiovascular (CV) Outcomes Associated with Treatment Exposures, Hazard Ratios (95% CI)CV DeathIschemic Heart DiseaseCardiomyopathyStrokeOther Vascular DiseaseDysrhythmiaAllogeneic vs. autologous donor2.4 (0.8-7.0)1.3 (0.6-2.9)0.9 (0.5-1.7)1.7 (0.5-5.3)0.7 (0.3-1.5)0.9 (0.6-1.5)Unrelated vs. related (allogeneic only)1.1 (0.4-3.5)0.7 (0.3-1.8)2.1 (0.8-5.2)0.5 (0.1-2.1)1.7 (0.5-5.4)0.9 (0.4-1.9)Peripheral blood vs. marrow (allogeneic only)5.7 (1.3-25.3)1.1 (0.3-4.4)2.5 (0.7-9.2)3.7 (0.7-20.6)0.8 (0.2-4.2)1.9 (0.7-5.4)Chronic GVHD vs. none (allogeneic only)2.5 (0.7-9.4)1.8 (0.7-4.6)0.7 (0.3-1.6)2.3 (0.6-8.6)1.3 (0.4-4.6)1.2 (0.6-2.3)Anthracycline dose (all patients), mg/m2<200 vs. none2.2 (0.7-6.8)0.9 (0.4-2.2)1.6 (0.8-3.3)1.6 (0.6-4.8)1.3 (0.6-3.1)1.5 (0.8-2.7)200-299 vs. none3.3 (0.99-10.7)1.7 (0.6-4.5)1.8 (0.7-4.5)1.2 (0.2-5.9)2.0 (0.8-5.1)1.8 (0.9-3.5)≥300 vs. none2.8 (1.0-7.7)1.0 (0.5-2.3)2.1 (1.0-4.4)2.5 (0.8-7.5)1.1 (0.4-2.8)1.9 (1.1-3.3)Anthracycline dose (allogeneic), mg/m2<200 vs. none2.0 (0.4-9.7)1.3 (0.4-3.7)2.8 (0.97-8.3)1.8 (0.3-10.7)0.9 (0.3-3.2)1.9 (0.9-4.2)200-299 vs. none7.3 (1.3-39.6)2.8 (0.9-8.8)9.6 (2.7-34.2)5.2 (0.8-32.3)2.0 (0.3-11.6)1.5 (0.4-5.7)≥300 vs. none3.2 (0.9-11.3)1.1 (0.4-3.3)4.6 (1.8-12.0)4.5 (1.2-16.3)1.6 (0.5-5.2)2.0 (0.9-4.2)Radiation exposureTBI ≥10 vs. <10Gy/none0.9 (0.2-4.4)1.1 (0.4-3.0)0.6 (0.3-1.5)1.7 (0.5-5.3)0.8 (0.2-2.8)0.9 (0.4-1.9)Chest <15Gy vs. none0.6 (0.1-2.8)0.9 (0.3-2.3)1.4 (0.6-3.2)1.6 (0.5-5.6)0.6 (0.2-1.9)1.3 (0.6-2.5)Chest 15-39Gy vs. none0.9 (0.2-4.0)0.5 (0.1-1.8)1.3 (0.5-3.5)1.4 (0.4-5.2)0.7 (0.2-2.0)0.8 (0.4-1.7)Chest ≥40Gy vs. none1.4 (0.4-5.3)0.8 (0.2-3.2)0.6 (0.2-1.7)0 (-)0.8 (0.2-3.6)0.5 (0.2-1.5)All estimates adjusted for sex, race, age/year of HCT, allogeneic/autologous donor, TBI dose, and subsequent relapse/2nd HCT. Open table in a new tab

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2010.12.072