Late mortality in two-year survivors of hematopoietic cell transplantation (HCT) performed in children and adolescents: Report from the BMT-Survivor Study

Abstract

8507 Background: We assessed overall and cause-specific late mortality [death occurring 2 or more years (yrs) after HCT] in a retrospective cohort of 862 patients (pts), unedrgoing HCT between 1974 and 1998, before the age of 21 yrs, and surviving at least 2 yrs. Methods: Vital status information was obtained from medical records, National Death Index, and Social Security Death Index. Age- and sex-standardized mortality ratios (SMR) were calculated using US population mortality data. Results: Primary diagnoses included ALL (n=212), AML (n=205), SAA (n=113), HD/NHL (n=67), inborn errors of metabolism (IEM: n=81), and other diagnoses (n=184). Types of HCT included related donor (RD: n=496), unrelated donor (URD: n=186), and autologous (A-HCT: n=180). Median age at HCT was 9.3 yrs (0.1–20.9) and length of follow-up 10.1 yrs (2.0–28.4). A total of 182 (21%) late deaths were observed. The cohort was at a 20-fold increased risk of late death when compared with the general population. Leading causes of deaths included recurrence of original cancer (61%) and chronic graft vs. host disease (cGVHD) (12%). Excess mortality rates were also seen due to pulmonary complications (SMR=41.5, 95%CI,18.8–73.1) and SMs (SMR=24.0, 95%CI,13.1–38.2). The probability of living 10 or more yrs was 79.5±1.9%. Multivariate analysis for RD/URD-HCT revealed the risk of late death to be significantly higher in pts receiving TBI (RR=4.4,p<0.001), busulfan (RR=2.8,p=0.03), and those with cGVHD (RR=1.9,p<0.001). Use of cyclosporine (RR=0.5,p<0.001) and methotrexate (RR=0.6,p=0.03) were associated with decreased risk. Among pts receiving A-HCT, the risk of late death was significantly higher in females (RR=1.9,p=0.02). Conclusions: Late mortality rates remain elevated 15 yrs after HCT. Leading causes of death include relapse, pulmonary complications and SMs. No significant financial relationships to disclose.