Abstract
Introduction
HCT is frequently offered as a curative option for children with benign and malignant conditions. Improvement in HCT strategies have increased survival by approximately 10% per decade. Adult HCT survivors are at increased risk for chronic health conditions (Sun, Blood 2010), and premature death (Bhatia, Blood 2007; 2005). The magnitude of risk of these chronic health conditions and of premature death in childhood HCT survivors is not known.
Methods
Participants were drawn from the BMTSS, and included patients undergoing HCT between 1976 and 1998 at City of Hope or University of Minnesota. Participants were ≤21 years of age at HCT and were ≥2 yrs from myeloablative HCT. Participants completed a questionnaire addressing the diagnosis of physical health conditions (endocrinopathies, central nervous system compromise, cardiopulmonary dysfunction, gastrointestinal sequelae, musculoskeletal abnormalities, and subsequent malignancies), chronic GvHD (cGVHD), and sociodemographics. Chronic physical health conditions were graded using CTCAE v 3.0 (grade 1-5, ranging from mild to death due to chronic health condition). Relative risk (RR) regression was used to identify risk of health conditions and 95% confidence interval (CI). Information on vital status and cause of death was obtained from medical records, National Death Index, and Social Security Death Index, and compared with age-, sex-and calendar-specific mortality of the US general population (standardized mortality ratio [SMR]).
Results
The current study included 317 BMTSS participants. Median age at HCT was 7.9 yrs, and at study participation was 19.9 yrs; time from HCT was 10.3 yrs; 42% were female, 86.7% were non-Hispanic white, and 79% underwent allogeneic HCT. The most frequent indications for HCT included AML (27%), ALL (21%), SAA (13%), lymphoma (6%), and CML (5%). Total body irradiation (TBI) was used in 61% of 2 year survivors, and cGvHD was reported in 26%. Health Conditions: The cumulative incidence of a chronic health condition (grade 1-5) was 56% (95% CI: 51%-60%) at 15 years after HCT, with a cumulative incidence of 25% (95% CI: 20%-30%) for severe/life-threatening or fatal condition (grade 3-5, Figure). The highest incidence of grade 3-5 conditions was in allogeneic HCT recipients with cGvHD (32% at 15 years, 95% CI: 20%-44%; Figure). Risk Factors: After adjustment for age at HCT, follow-up, ethnicity/race, diagnosis, relapse risk at HCT, and treatment era, female participants were 1.2 (1.0-1.4, p=0.02) times more likely to report a chronic health condition, and 1.6 (1.1-2.4, p=0.01) times more likely to report a severe/life-threatening/fatal condition. Exposure to TBI was associated with a 1.3-fold (1.0-1.5, p=0.02) risk of a chronic health condition, and a 2.6-fold (1.4-4.91, p=0.003) risk of a severe/life-threatening/fatal condition compared to chemotherapy-only conditioning. Among allogeneic HCT recipients, cGvHD was associated with a 2.0-fold (1.2-3.2, p<0.01) risk of severe/life-threatening/fatal conditions when compared to survivors without cGvHD. Healthcare utilization: 92% of the survivors carried health insurance and 68% had been seen at their transplant center within the past 2 yrs. Late mortality: Overall survival in 2 year survivors was 80% at 10 years (68% autologous, 83% allogeneic, p<0.01). The primary cause of death included primary disease (61%), secondary cancer (8%), cGvHD (6%), cardiopulmonary compromise (5%), and other causes (21%). The cohort was at a 22-fold (SMR 22.0, 18.9-25.5, p<0.01) increased risk of premature death compared to age-and sex-matched general population. Female participants, those treated with TBI, and autologous HCT survivors had the highest risk of premature death (Table).
Conclusions
Childhood HCT survivors carry a substantial burden of morbidity, years following completion of therapy, providing clear evidence for their close monitoring in a specialized setting targeting these high risk complications.
Disclosures:
No relevant conflicts of interest to declare.
Health outcomes in a national sample of American Indian and Alaska Native adults: Differences between multiple-race and single-race subgroups
