Burdern of Long-Term Morbidity after Hematopoietic Cell Transplantation: A Report from the Bone Marrow Transplant Survivor Study (BMTSS).

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Long-term survival is an expected outcome after HCT. However, no study has assessed the burden of long-term morbidity in these survivors, or attempted to identify subpopulations at highest risk for severe, debilitating conditions. In this study, we determined the prevalence and severity of chronic health conditions in a large population of long-term HCT survivors and compared these outcomes with their siblings. BMTSS, a collaborative effort between City of Hope National Medical Center and University of Minnesota, examined self-reported chronic health conditions in individuals who underwent HCT between 1976 and 1998, and survived two or more years. A severity score (grade 1 through 4, ranging from mild to life-threatening or disabling) was assigned to each health condition according to the Common Terminology Criteria for Adverse Events (version 3). A partial list of conditions graded as severe or life-threatening (grade 3 or 4) included congestive heart failure, second malignant neoplasms, coronary artery disease, cerebrovascular accident, renal failure/dialysis/renal transplant, and active chronic graft vs. host disease. Adverse psychosocial outcomes were not included. Cox proportional-hazard models were used to estimate hazard ratios and their 95% confidence intervals. We compared the prevalence and severity of chronic conditions in 1013 HCT survivors (455 autologous, 460 related donor, and 98 unrelated donor HCT survivors) with 309 siblings. The median age at study participation was 44 (range 18–73) and 45 years (range 17–79) for survivors and siblings, and the median follow-up for the survivors was 7.3 years (range 2–28) from HCT. Among the 1013 survivors, 69% had at least one chronic condition, and 29% had a severe or life-threatening condition (grade 3 or 4). The comparable figures in siblings were 39% and 7%, respectively (p<0.001 compared to survivors). After adjustment for age at HCT, sex and race/ethnicity, survivors were 2.4 times as likely as their siblings to develop any chronic health conditions (95%CI, 2.0–2.9), and 4.5 times more likely to develop severe/life threatening conditions (95%CI, 3.0–6.7). Groups at highest risk for a severe or life-threatening condition are summarized in the Table. Among survivors, the cumulative incidence of a chronic health condition reached 84% at 20 years post HCT, with a cumulative incidence of 55% for severe/life threatening conditions at 15 years after HCT. The chronic health burden of this population is significant, and life-long follow-up of patients who receive transplantation is recommended.Table:Groups at highest risk for severe or life-threatening conditionRisk FactorsRelative Risk95% CISiblings1.0__CML5.83.8–8.9AML4.93.2–7.5ALL5.23.3–8.3Allogeneic sibling donor5.93.9–8.7Unrelated donor7.44.9–11.1TBI5.03.4–7.5