Feasibility of hypomethylating agents followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome

Abstract

The role of hypomethylating agent therapy (HMT) as a bridge to allogeneic hematopoietic cell transplantation (alloHCT) in patients with myelodysplastic syndrome (MDS) remains undetermined. We investigated the feasibility of HMT followed by alloHCT in patients with MDS. In all, 19 patients who received HMT followed by alloHCT were analyzed. A total of 7 patients were classified as low-risk and 12 as high-risk, based on World Health Organization (WHO) classification at the time of HMT. HMT consisted of decitabine in 9 patients and azacitidine in 10. After HMT, two patients achieved CR, six mCR, three hematologic improvement alone, and six SD in terms of best response. HMT did not alter WHO classification in 15 patients (79%), whereas 1 patient (5%) improved and 3 (16%) progressed to AML. Most patients (95%) received a non-myeloablative conditioning regimen based on fludarabine/BU/anti-thymocyte globulin, and peripheral blood-mobilized stem cells. Neutrophil and platelet engraftments were achieved in 95 and 79% of patients, respectively. The incidences of acute and chronic GVHD were 42 and 26%, respectively. In all, 2-year OS rates were 68%, and the overall outcomes of those who achieved CR/mCR with HMT tended to be superior to those without CR/mCR. HMT followed by alloHCT was a feasible and effective treatment strategy for patients with MDS.

Azacitidine Pre-Treatment Followed by Reduced-Intensity Stem Cell Transplantation in Patients with Higher-Risk Myelodysplastic Syndrome

“…66.7% of patients received planned allo-SCT, and these patients demonstrated a 3-year PFS rate of 39.7% and a 3-year OS rate of 42.9%. These results are similar to data from retrospective studies [8,9,19,20] . Intention-to-treat analysis of all 21 patients gave a 3-year PFS rate of 27.8% (95% CI 7.4-48.2) and a 3-year OS rate of 30.3% (95% CI 10.1-50.5).…”

“…Previous prospective studies sub-analysed only patients who received an allograft and patients who received decitabine as a pre-treatment agent. Most retrospective studies of HMA pre-treatment before allo-SCT in patients with MDS included only 50% of the higher-risk patients according to the IPSS [8,9,19,20] . They reported 1-or 2-year OS of 47-63%; however, half of the study population were lower-risk patients, which may explain the favourable results.…”

Achieving stringent CR is essential before reduced-intensity conditioning allogeneic hematopoietic cell transplantation in AML

“…For those at a higher risk, MAC HCT might be considered to improve the leukemic control. 2,51,52 In patients who do not meet strict CR criteria and so are unfit to undergo a MAC allo-HCT, experimental targeted therapies and/or cellular therapies (for example, tyrosine kinase inhibitors in FLT-3-positive patients, hypomethylating agents 53 or haploidentical natural killer cell therapy 54 ) might be preferred over further conventional drug consolidation as a bridging therapy to allo-HCT. Consolidation chemotherapies did not improve allo-HCT outcome before either MAC or RIC transplantation.…”

Azacitidine salvage therapy for relapse of myeloid malignancies following allogeneic hematopoietic SCT

“…As reported by Kim et al 19 and Damaj et al, 20 AZA has proven to be an effective treatment in serving as a bridge to allo-HSCT. However, disease relapse following allo-HSCT remains challenging 21 and current attempts to treat these patients are still disappointing.…”