Chronic Myelomonocytic Leukemia and Related Disorders Provide Particular Disease-Specific Challenges to Effective Bone Marrow Transplant: a Multicenter Experience.

Abstract 4561

Chronic myelomonocytic leukemia (CMML) typically has a dire prognosis with limited treatment options. We retrospectively reviewed the outcomes of 41 patients diagnosed with CMML (n= 35) or MDS/MPD overlap (n=6) who underwent allogeneic stem cell transplantation at three centers (University of Minnesota (n= 19), Johns Hopkins University (n=11), and the Cleveland Clinic (n=11)) between1990-2009. The majority of patients were male (59%) with a mean age of 51. At diagnosis nearly half of the patients had normal cytogenetics (n=20, 49%) with abnormalities of chromosome 7 the most commonly identified clonal finding (n=5, 12%). The majority had <5% blasts (n=22, 54%), and the majority had an MD Anderson Prognostic Score (MDAPS) of 2 (n=16, 39%) or 3 (n=13, 32%) at diagnosis. Fifteen patients (37%) received no pre-transplant therapy while 12 (29%) received hydroxyurea, 11 (27%) induction-type chemotherapy, and 3 (7%) miscellaneous other therapies. Nine patients (22%) had progressed to AML prior to transplant. At the time of transplant, blast percentage was <5% in the majority (n=23, 56%) of patients and more than half of patients now had a MDAPS of 1 (n=13, 32%) or 2 (n=12, 32%). Comorbidity index (HCT-CI) at transplant was retrospectively calculated on 32 patients and was 0 (n=5, 12%), 1–2 (n=13, 32%), or 3+ (n= 15, 37%). Myeloablative conditioning was used in 23 (56%) and stem cell source was bone marrow in 14 (34%), PBSC in 16 (39%), and UCB in 9 (22%). The majority of donors were matched siblings (n=22, 54%) while unrelated donors (URD) (n=16, 39%) and haploidentical donors (n=3, 7%) comprised the remaining. Graft versus host disease (GVHD) prophylaxis consisted of a calcineurin inhibitor (cyclosporine or tacrolimus) + methotrexate or mycophenolate mofetil (MMF) in the majority of patients (n=29, 71%) with the remainder receiving post-transplant cyclophosphamide (n=6, 15%), elutriation (n=2, 5%), or calcineurin inhibitor alone (n=4, 10%). While the median time to follow-up was only 5.8 months (range 0.5–140), 24 patients had died by one year and there was extensive follow-up available in the surviving patients. Overall survival (OS) for the entire cohort at 1 and 3 years was 41% (95% CI, 26–56%) and 16% (95% CI, 6–30%), respectively. No disease or transplant factors significantly impacted survival. Progression free survival (PFS) at 1 and 3 years was 29% (95% CI, 16–43%) and 16% (95% CI, 7–29%), respectively. Sibling donor showed improved PFS at both 1 (45%, 95% CI 24–64%), (p=0.027) and 3 (27%, 95% CI 10–46%), (p=0.04) years. Transplant related mortality (TRM) at Day +100 and 1 year was 27% (95% CI, 13–40%) and 41% (95% CI, 26–57%) respectively. Age at transplant, year transplanted, HCT-CI at transplant, conditioning intensity, donor source, transplant site, or presence of acute graft versus host disease (GVHD) did not impact TRM. Relapse at 1 and 3 years was 29% (95% CI, 15–44%) and 40% (95% CI, 23–56%), respectively. High MDAPS at diagnosis and sibling donor source were the only significant factors impacting relapse. At 1 year, those with an MDAPS of 3–4 had a 53% chance of relapse compared with 29% with a score of 0–1 (p=0.05) and those with a sibling donor had a 9% relapse incidence compared with 50% in the URDs and 67% in the haploidentical setting (p=0.003). Interestingly the presence of acute GVHD at Day +100 was not protective against relapse (40% incidence at 1 year in those with aGVHD versus only 19% for those without). Our data suggest that high MD Anderson Prognostic score at diagnosis predicts for high incidence of relapse post allogeneic stem cell transplantation while a sibling donor source improves rates of relapse and progression free survival. Our data highlight the need for improved CMML treatment paradigms. Augmentation of pre and post transplant therapy including maintenance therapy post transplant are possible approaches to improve outcomes and could be considered for prospective trials.