Allogeneic Hematopoietic Cell Transplantation for Elderly Patients: Prognosis Determined By Disease Risk Index
Authors: He Fiona C. , Lazaryan Aleksandr , Cao Qing , Brunstein Claudio G , Holtan Shernan G. , Warlick Erica D. , Ustun Celalettin , McClune Brian , Arora Mukta , Weisdorf Daniel J. , Bejanyan Nelli 
Published: October 2019

Abstract
Survival of elderly patients with hematological malignancies remains suboptimal despite many older adults receiving reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT). We studied the impact of disease risk index (DRI) on clinical outcomes of 196 elderly patients (≥60 years old) with hematological malignancies receiving RIC alloHCT between 2000-2013. Median age at transplant was 64.8 years (range, 60-75; 53% age 60-64 and 47% age ≥65). More comorbidities (HCT-CI ≥3) were present in 70 patients (35.7%) and Karnofsky performance score (KPS) was < 80% in 34 patients (17.3%) prior to transplant. Peripheral blood or bone marrow allografting was performed in 100 patients (51.1%) and umbilical cord blood allografting in 96 patients (48.9%). DRI classified 12 patients (6.1%) as low risk (LR), 146 patients (74.5%) as intermediate risk (IR), and 38 patients (19.4%) as high or very high-risk (HR/VHR). Neutrophil engraftment at day 42 did not differ between LR/IR and HR/VHR (95% vs. 100%, p=.40), whereas platelet engraftment at 6 months was significantly lower for HR/VHR (76% vs. 58%, p=.08). Treatment related mortality (TRM) at 2 years was similar in LR/IR and HR/VHR (28% vs. 34%, p=.12). Overall relapse incidence was 30% in the entire cohort and increased in HR/VHR (26% for LR/IR vs. 44% for HR/VHR; p<.01). Notably, 2-year disease free survival (DFS) and overall survival (OS) were both significantly lower in HR/VHR groups. DFS was 39% in entire cohort (44% for LR/IR vs. 21% for HR/VHR; p<.01), and OS in entire cohort was 47% (52% for LR/IR vs. 29% for HR/VHR; p<.01; Figure). For LR/IR and HR/VHR DRI groups, the incidence of grade II-IV acute GVHD was similar (41% and 47% at 6 months, p=.32) and the incidence of chronic GVHD was similar (35% and 31% at 2-years, p=.07). GVHD and relapse free survival (GFRS) at 2-years was significantly worse for HR/VHR DRI group (25% for LR/IR vs. 0% for HR/VHR; p<.01). All clinical outcomes were similar between those 60-64 and ≥65 years of age. In multiple regression analysis, after adjusting for a graft source, platelet recovery was worse for HR/VHR DRI group (HR=0.56; 95% CI 0.35-0.91; p=.02), while neutrophil engraftment was not influenced by DRI. HR/VHR DRI was a risk factor for increased risk of relapse after alloHCT (HR=2.05; 95% CI 1.14-3.69; p=.02). After adjusting for graft source, KPS and year of HCT, treatment failure (inverse of DFS; HR=1.83; 95% CI 1.16-2.87; p=.02) and overall mortality (HR=1.87; 95% CI 1.16-3.02; p=.01) were significantly increased for HR/VHR DRI group. Although DRI did not affect the risk of acute or chronic GVHD, GRFS was significantly worse for patients with HR/VHR DRI (HR=2.13; 95% CI 1.46-3.11; p<.01). We conclude that in this cohort of elderly patients, worse DRI remains a significant prognostic factor for post-transplant relapse, treatment failure, mortality and GRFS. While eligible elderly patients up to age 75 with hematologic malignancies should be considered for RIC alloHCT, alternative or novel therapies should be considered for those with HR/VHR DRI.
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Disclosures
No relevant conflicts of interest to declare.