Abstract

Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative treatment for patients with chronic myelomonocytic leukemia (CMML), however there little data regarding prognostic factors and transplant outcomes. Recently a CMML-specific prognostic scoring system (CPSS) was validated in the non-transplant setting [1Such E. Germing U. Malcovati L. et al.Development and validation of a prognostic scoring system for patients with chronic myelomonocytic leukemia.Blood. 2013 Apr 11; 121: 3005-3015Crossref PubMed Scopus (227) Google Scholar]. We sought to validate this scoring system in the HCT setting. We identified 209 adult patients undergoing HCT for CMML reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 2001 through 2012. The median age at transplant was 57 years (range 23-74), with a majority being male (70%). Most had Karnofsky Performance Score of 90-100% (61%). Eighty eight (42%) patients had low/intermediate-1, while 79 (38%) had intermediate-2/high, and 42 (20%) had missing CPSS scores. Based on CPSS definition, 50% had favorable, 19% had intermediate, 17% had poor risk, and cytogenetic data were missing for 14%. Median time from diagnosis to transplant was 8 months (range 2-170). HCT were performed with HLA identical siblings (35%), matched unrelated donors (45%), partially matched unrelated donors (15%), or mismatched/indeterminate matched unrelated donors (4%). Patients received bone marrow (16%) or peripheral blood (84%). Patients received myeloablative (51%), reduced-intensity (41%), non-myeloablative (< 5%) or other (<4%) conditioning regimens. GVHD prophylaxis was cyclosporine-based (37%), FK-506-based (61%), methotrexate alone (<1%) or missing (<1%). Median follow up was 51 months (range of 3-122). On multivariate analyses, CPSS scores, KPS, and graft source were significant predictors of overall survival (p=0.004, p=0.01, p=0.01 respectively; CPSS and OS figure below). Higher CPSS scores were not associated with disease free survival (DFS), relapse, or transplant related mortality (TRM) (p=0.2, p=0.1, p=0.08, respectively). To investigate why higher CPSS scores were associated with higher mortality, we performed analysis restricted to patients with relapse following HCT. Those with intermediate-2/high risk had nearly two-fold increase in risk of death after relapse compared to those with low/intermediate-1 CPSS scores. Corresponding rates for low/intermediate-1 risk groups, OS at 1 year, 3 years, and 5 years were 61%, 48%, and 44% respectively and for intermediate-2/high risk groups were 38%, 32%, and 19% respectively. OS of patients who received pre-HCT treatment with hypomethylating agents, chemotherapy, or both was not different compared to those who received no therapy prior (p=0.96). In summary, CPSS scores, lower KPS scores, and bone marrow as graft source were associated with poorer outcomes following HCT.

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