Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation for Hematologic Malignancies: Outcomes Are Not Impaired in Patients of Advanced Age.
Authors: Koreth John , Aldridge Julie , Kim Haesook T. , Alyea Edwin P. , Cutler Corey , Armand Philippe , Ritz Jerome , Antin Joseph H. , Soiffer Robert J. , Ho Vincent T. 
Published: October 2019

Abstract
Abstract 1208
Poster Board I-230
The incidence of hematologic malignancies increases with age but by convention older patients have often been excluded from the curative approach intrinsic to allogeneic hematopoietic stem cell transplantation (HSCT). Limited information on reduced-intensity conditioning (RIC) HSCT outcomes in patients of advanced age restricts our ability to advocate this curative therapy for them, despite its lower toxicity compared to myeloablative HSCT.
We report a retrospective analysis of 158 patients aged ≥60 yrs that underwent a consistent fludarabine/busulfan RIC HSCT for hematologic malignancies at DFCI between Jan 2002-Jun 2008. The median age was 63 yrs (range, 60-71). The principal diseases were myeloid in 70 % and lymphoid in 27%. 76% had high-risk disease (e.g., advanced stage or prior therapy). 12% had prior autologous transplants. Matched-unrelated, matched-related and mismatched adult donors were used in 56%, 34%, and 10% respectively. 96% received peripheral blood stem cell infusions. Graft-versus-host-disease (GVHD) prophylaxis included tacrolimus (91%) ± sirolimus (59%).
The median follow-up among survivors was 34 months (range, 12.0-85.7). Median time to neutrophil and platelet recovery was 13 (range, 2-70) and 20 days (range, 11-78) respectively. Cumulative incidence of grade II-IV acute GHVD at 200 days was 19.6%, and chronic GVHD at 2 yrs was 45.9%. Cumulative incidence of relapse and non-relapse mortality (NRM) at 2 yrs was 57.1% and 10% respectively. Overall and progression-free survival (OS, PFS) at 2 years was 46% (95% CI, 38-54) and 35% (95% CI, 28-43) respectively.
We compared outcomes in 110 patients aged 60-64 yrs (median 62 yrs) vs. 48 patients aged ≥65 yrs (median 67 yrs). The median follow-up among survivors was 35 (range, 12-85.7) and 32.4 months (range, 12.7-72.8) respectively. The groups did not differ significantly for covariates tested. Median time to neutrophil and platelet recovery was 13 (2-70) vs. 15 days (3-33), and 20 (11-78) vs. 19 days (12-60) respectively. Cumulative incidence of grade II-IV acute GHVD at 200 days was 18.2% vs. 22.9% (p=0.52), and of chronic GVHD at 2 yrs was 51.8% vs. 32.5% (p=0.01). Cumulative incidence of relapse and NRM at 2 yrs was 55.1% vs. 61.3% (p=0.31), and 10.5% vs. 8.3% (p=0.84) respectively. OS and PFS at 2 years was 49% (95% CI, 39-58) vs. 41% (95% CI, 26-54) (p=0.11) and 36% (95% CI, 27-45) vs. 35% (95% CI, 22-49) (p=0.24). In a multivariate Cox model disease-risk (high vs. low) was significantly associated with poorer PFS (HR 1.99, 95% CI 1.17-3.41, p=0.01) and OS (HR 1.80, 95% CI 1.03-3.17, p=0.04); and diagnosis (AML/MDS vs. other) was significantly associated with poorer PFS (HR 1.63, 95% CI 1.02-2.60, p=0.04). Age ≥65 yrs (vs. 60-64 yrs) was not associated with poorer PFS (HR 1.14, 95% CI 0.72-1.79, p=0.58) or OS (HR 1.32, 95% CI 0.83-2.11, p=0.24).
In appropriately selected older patients RIC HSCT is well-tolerated with reasonable survival, in a cohort of patients with otherwise fatal illnesses. As in younger patients, relapse is the major cause of death. In patients aged ≥65 yrs, treatment-related toxicities are not increased and survival is comparable to those aged 60-64 yrs. RIC HSCT should not be excluded solely based on patient age. Novel strategies to reduce relapse post-HSCT should be prioritized.

Disclosures:
No relevant conflicts of interest to declare.