Treatment with Hypomethylating Agents before Allogeneic Stem Cell Transplant Improves Progression-Free Survival for Patients with Chronic Myelomonocytic Leukemia

Abstract

The treatment of patients with chronic myelomonocytic leukemia (CMML) with transplant has not been optimized. We retrospectively reviewed the data for 83 consecutive patients with CMML (47 with CMML-1/2 and 36 with CMML progressed to acute myeloid leukemia) who received an allogeneic stem cell transplant at our institution between April 1991 and December 2013 to identify factors associated with improved survival and determine whether treatment with hypomethylating agents before transplant improves progression-free survival. The median age of the cohort was 57 years. Seventy-eight patients received induction treatment before transplant, with 37 receiving hypomethylating agents and 41 receiving cytotoxic chemotherapy. Patients treated with a hypomethylating agent had a significantly lower cumulative incidence of relapse at 3 years post-transplant (22%) than those treated with other agents (35%; p=0.03), whereas TRM at 1 year post-transplant did not significantly differ between the groups (27% and 30%, respectively; p=0.84). The lower relapse rate resulted in a significantly higher 3-year PFS rate in patients treated with a hypomethylating agent (43%) than in those treated with other agents (27%; p=0.04). Our data support the use of hypomethylating agents before allogeneic stem cell transplantation for patients with CMML to achieve morphologic remission and improve progression-free survival of these patients. Future studies are needed to confirm these findings.

Allogeneic Hematopoietic Cell Transplantation for Adult Chronic Myelomonocytic Leukemia

“…The median age of our patients was 57 years, older than in other reported studies. 11–18, 22 The median follow up in our study is 51 months, longer than in most other reported studies. 11–13, 15–18, 23–27 Subjects underwent either myeloablative or RIC preparative regimen.…”

“…This is contrary to a recent publication from Kongtim et al that reports lower relapse and improved progression-free survival for patients treated with hypomethylating agents prior to alloHCT. 18 …”

“…9,10 Allogeneic hematopoietic cell transplant (HCT) remains the only potentially curative treatment and outcomes following transplant are sparse. 11–18 Some of these reports suggest that the percentage of blasts present in the peripheral blood, cytogenetic abnormalities, and transplant type may have prognostic importance following transplant. However, the studies are limited by small numbers of patients from single institutions and no definitive conclusions have been made.…”

Chronic myelomonocytic leukemia “myelodysplastic type’’ in transformation to acute myeloid leukemia – diagnostic and therapeutic options: case report and literature review / Leucemie mielomonocitară cronică forma mielodisplazică în transformare spre leucemie acută mieloidă – diagnostic și opțiuni terapeutice: prezentare de caz și revizuirea literaturii

“…Data for Allo-HSCT results in CMML can be found in the reports on allo-HSCT in MDS and MPN or in retrospective studies on small number of CMML transplanted patients. There are no randomized prospective (Table 2) [20][21][22][23][24][25][26][27][28][29][30][31]. In 2015 two reports ''specifically'' focused on the evolution of allo-HCST in CMML appeared.…”

Are next-generation sequencing results knocking on Heaven’s door for transplantation planning in chronic myelomonocytic leukemia?

“…A recent multicenter retrospective study with 1,656 CMML patients of whom 89 received an allogeneic HCT demonstrated the benefit of HCT for patients with higher-risk disease as determined by the CPSS 11 and multiple retrospective studies have documented a 3-year OS rate of 30-40%. [12][13][14][15] For high-risk transplant-ineligible and/or lower-risk patients the most widely used therapies are hydroxyurea, hypomethylating agents, and best supportive care. Recent evidence suggests that hypomethylating agents might be superior to hydroxyurea.…”