Allogeneic Transplantation for Chronic Myelomonocytic Leukemia (CMML) Is Associated with High Disease-Free Survival Even in the Setting of High-Risk Disease

Abstract

Background: CMML has a poor prognosis with a median overall survival of about 30 months and a 15-20% risk of transformation to acute myeloid leukemia. For high-risk patients the median survival is 9 months. The only curative therapy is allogeneic hematopoietic stem cell transplantation (allo-HSCT). While several prognostic models have been proposed in CMML, their predictive value in allograft recipients is not well established. We report the outcome of allo-HSCT in 28 patients (pts) with CMML, and the relationship between five CMML prognostic scoring systems and post-transplant disease-free survival (DFS).Methods: 28 pts with CMML underwent allo-HSCT at MSKCC between 1/2002 and 2/2014. Pt and transplant characteristics are summarized in Table 1. Of the 28 pts, 6 had progressed to CMML-2 and 7 to AML pre-transplant. Except for 3 pts, all received chemotherapy before cytoreduction to decrease disease burden and all patients had <20% blasts prior to conditioning. Five prognostic scoring systems were used to classify the patients into low and high risk: 2 MDS and 3 CMML-specific models. T-cell depleted pts (n = 16, 60%) received myeloablative conditioning (12 busulphan/ melphalan/ fludarabine/ rabbit ATG and 4 TBI-based) whereas 12 pts (40%) received unmodified grafts with varying conditioning intensity. The source of HSC was 23 PB, 2 BM, and 3 cord blood.Results All pts had sustained donor engraftment. The cumulative incidences of day 100 grade II-IV acute graft-versus-host disease (GVHD) and 1-year chronic GVHD were 18% (95%CI:3-32) and 17% (95%CI:1-33), respectively. The 1-year incidence of transplant-related mortality was 7% (95%CI:0-17) with the most common transplant-related cause of death being infection. Three pts relapsed for a 1-year incidence of 13% (95%CI:0-26). These patients died of their disease. With a median follow-up of survivors of 3.3 years (range 3 months-11.6 years), the 3-year Kaplan-Meier estimate of overall survival is 74% (95%CI: 51-88) and DFS is 71% (95%CI: 47-85). All pts classified as having high-risk disease had similar survival to low risk disease pts (Table 2).Conclusion: This preliminary data suggests that allo-HSCT can achieve a high DFS in pts with CMML, even in the setting of high-risk disease. Thus, allo-HSCT should potentially be considered in all patients with CMML including pts who have a dismal prognosis based on current prognostic scoring systems.Table 1Patient and transplant characteristicsCharacteristicsN=28Age , years (range)60 (12-69)GenderMale Female- 18 (64%) 10 (36%)BM Blasts at diagnosis (%)<5 5-9 10-19- 13 (46%) 7 (25%) 8 (29%)Diagnosis karyotype risk group per Spanish ScoreGood Intermediate/Poor- 17 (60%) 11 (40%)WHO classification at diagnosisCMML-1 ( <10 % BM blasts) CMML-2 (10-20% BM blasts)- 20 (71%) 8 (29%)FAB classification at diagnosisMyelodysplastic subtype (< 13000 WBC) Myeloproliferative subtype (> 13000 WBC)- 14 (50%) 14 (50%)WHO status at progression (highest disease)CMML -1 CMML -2 AML- 12 (43%) 9 (32%) 7 (25%)Pre-transplant therapyNo chemotherapy Hypomethylating agent AML type chemotherapy- 5 (18%) 10 (36%) 13 (46%)BM Blasts pre-transplant (%)<5 5-9 10-19- 21 (75%) 4 (14%) 3 (11%)Transplant conditioningMyeloablative Reduced intensity- 22 (78%) 6 (22%)Donor8/8 HLA Matched related donor 8/8 HLA Matched unrelated donors HLA-mismatched unrelated donors Cord blood- 13 (46%) 9 (32%) 3 (11%) 3 (11%)GVHD prophylaxisT cell depletion Calcineurin inhibitor- 16 (60%) 12 (40%)Table 2:DFS per risk level defined by different prognostic models *CMML- specific scoring systemsPrognostic ScoreN3 year DFSIPSS-R0-1 2-3- 11 17- 83% 63%MDASC0-1 2-3- 21 7- 71% 69%MDAPS *0-1 2-3- 16 12- 68% 74%Mayo * 0-1 2- 10 18- 56% 76%Spanish Score *0-1 2-3- 20 8- 68% 75% DisclosuresBoulad:Genzyme Sanofi: Trials partially funded by Genzyme Sanofi Other.