Graft-Versus-Host Disease-Free, Relapse-Free Survival (GRFS) after Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplant (HCT) in Older Patients with Myeloid Malignancies

HCT remains the only curative treatment option for many patients (pts) with myeloid malignancies. The decision to offer HCT for older pts with myeloid malignancies is challenging given their high rate of transplant related morbidity and mortality. Recently, a composite endpoint of GRFS was proposed to aid physicians and pts in treatment decision; however, the rate of GRFS in older pts with myeloid malignancies undergoing reduced intensity (RIC) HCT is not known. We retrospectively analyzed transplant data on pts >60 years old with AML, MDS and CMML who received RIC HCT between 5/2000-11/2014. The GRFS outcome included grade 3-4 acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse, or death from any cause (Holtan et al, Blood 2015). For pts with multiple events, the earliest event was considered for GRFS endpoint. All outcomes were calculated from the date of HCT. Pts who did not have any events within 1 year of HCT were censored at 1 year. Prognostic factors for GRFS were identified with Cox proportional hazards analysis. A total of 93 pts were included: 53 (57%) AML, 33 (35%) MDS, and 7 (8%) CMML. Median age was 64 years (range, 60-73), 61% were males. Pts distribution per HCT comorbidity index for low, intermediate, and high risk was: 19 (20%), 32 (34%), and 42 (45%) and per ASBMT disease risk index: 50 (54%), 11 (12%), and 32 (34%), respectively. A total of 39 (42%) received graft from HLA identical sibling, 37 (40%) from matched unrelated donors, and 17 (18%) from mismatched donors (2 haplo, 10 UCB, 5 unrelated). Majority of pts received PBSC grafts (82 pts, 88%). Conditioning regimens: 43 (46%) received Bu/Flu, 37 (40%) Flu/TBI, 10 (11%) Flu/Cy/TBI/ATG, and 3 (3%) others. GVHD prophylaxis included: FK/MMF in 48 pts (52%), CSA/MMF 40 (43%), and others 5 (5%). The median time from diagnosis to HCT was 7 months (range, 3-116). Four pts (4%) had prior autologous stem cell transplant (ASCT). Overall survival, relapse-free survival, and GRFS at 1 year were 57%, 46%, and 25% respectively (Figure 1). GRFS at 1 year was 26% for AML, 27% for MDS, and 14% for CMML pts. First GRFS event was: cGVHD in 25 pts (37%), relapse 24 (35%), death 12 (18%), and grade 3-4 aGVHD in 7 pts (10%). In a multivariable analysis, only prior ASCT impacted GRFS (HR 3.5, 95% CI 1.3-9.7, p= .02). In pts ≥60 years with myeloid malignancies who receive RIC HCT, 1-year GRFS is ∼25%. Traditional prognostic factors (e.g., age, HCT CI score, donor/graft source, disease risk) were not predictive of GRFS in this population. Our findings will assist clinicians in counseling older patients with these diseases about HCT. A larger study is also needed to validate our findings.