Survival of Older Patients with AML and MDS after Allogeneic Hematopoietic Transplantation Is Best Determined By Combining Disease Risk and Comorbidity Indices.

Disease Risk Index (DRI) and Hematopoietic Cell Transplant Comorbidity Index (HCT-CI) are independently validated and powerful pretransplant prognostic tools for overall survival (OS) of patients receiving allogeneic HCT (alloHCT) for hematological malignancies. Here we examined the prognostic significance of the DRI in conjunction with HCT-CI on OS among 341 elderly patients (≥60 years old) with AML (n=214) and MDS (n=127) who received alloHCT from 2005 to 2016. The median age at alloHCT for all patients was 66 (range, 60-76) years: 42% were age 60-64, 43% age 65-69 and 15% age ≥70. DRI classified patients as low/intermediate risk (LR/IR DRI, 63%) or high/very high risk (HR DRI, 37%). Nearly half of the patients had many comorbidities (HCT-CI ≥3) and 30% of all patients had lower Karnofsky Performance Status score (KPS <90%) at transplant. Myeloablative conditioning was used in 58% of all patients and 58% received matched unrelated donor, followed by matched related donor (26%) or mismatched donor (16%) alloHCT. Majority of patients (94%) received a peripheral blood allograft and 67% of all patients were CMV seropositive. There were no significant differences between LR/IR DRI group and HR DRI group in regards to any patient or transplant related characteristics examined. OS at 2 years was 50% (45-56%) for the entire cohort. When combined effect of DRI and HCT-CI was considered, overall mortality risk significantly increased with higher HCT-CI within each DRI group, resulting in 2-year OS of 66.2% in LR/IR DRI+HCT-CI 0-2 vs. 56.2% in LR/IR DRI+HCT-CI ≥3 vs. 47.1% HR DRI+HCT-CI 0-2 vs. 34.8% HR DRI+HCT-CI ≥3 groups (p <0.0001) (Figure). In multivariate Cox regression analysis, after adjusting for age, CMV serostatus and conditioning intensity the HR DRI (hazard ratio (HR) =2.2, 95% CI 1.6-3.0; p <0.001) and HCT-CI ≥3 (HR=1.5, 95% CI 1.0-2.1; p =0.04) were the only factors independently predictive of higher overall mortality. Increasing age (HR=1.3, 95% 0.9-1.9 CI; p =0.13 for age 65-69, and HR=1.0, 95% 0.6-1.6 CI; p =0.097 for age ≥70) and diagnosis (HR=0.9, 95% 0.6-1.3 CI; p =0.6 for MDS) had no significant impact on survival. Our findings suggest that most elderly patients with AML and MDS benefit from potentially curative alloHCT. Survival was worse for patients with combined high risk DRI and many comorbidities (HR DRI+ HCTCI ≥3). Thus, combining DRI and HCT-CI can serve as an effective pre-HCT tool to prognosticate survival after alloHCT. Age alone should not be a limiting factor in transplant decision making in otherwise eligible patients with AML and MDS. [ABSTRACT FROM AUTHOR]