Upfront Allogeneic Stem Cell Transplantation after Reduced-Intensity/Nonmyeloablative Conditioning for Patients with Myelodysplastic Syndrome: A Study by the Société Française de Greffe de Moelle et de Thérapie Cellulaire

Abstract

Cytoreduction before allogeneic stem cell transplantation (allo-SCT) for patients with myelodysplastic syndromes remains a debatable issue. After excluding patients who had received preconditioning induction chemotherapy, we analyzed 128 consecutive patients with myelodysplastic syndrome who received reduced-intensity or nonmyeloablative conditioning (RIC/NMA) allo-SCT. Among them, 40 received azacitidine (AZA) before transplant (AZA group) and 88 were transplanted up front (best supportive care [BSC] group). At diagnosis, 55 patients had intermediate 2 or high-risk scores per the International Prognostic Scoring System and 33 had a high cytogenetic risk score. Progression to a more advanced disease before allo-SCT was recorded in 22 patients. Source of stem cells were blood (n = 112) or marrow (n = 16) from sibling (n = 78) or HLA-matched unrelated (n = 50) donors. With a median follow-up of 60 months, 3-year overall survival, relapse-free survival, cumulative incidence of relapse, and nonrelapse mortality were, respectively, 53% versus 53% (P = .69), 37% versus 42% (P = .78), 35% versus 36% (P = .99), and 20% versus 23% (P = .74), for the AZA group and BSC group, respectively. Multivariate analysis confirmed the absence of statistical differences in outcome between the AZA and BSC groups, after adjusting for potential confounders using the propensity score approach. The absence of cytoreduction before RIC/NMA allo-SCT did not seem to alter the outcome. However, our results emphasize the need to perform prospective protocols to delineate the role of debulking strategy and to identify subsets of patients who may benefit from this approach.

The European Hematology Association Roadmap for European Hematology Research: a consensus document

“…354 Prospective randomized trials are necessary to assess whether a short course of chemotherapy the week prior to conditioning in AML or azacytidine in refractory anemia with excess blast patients will reduce the risk of post-transplant relapse.…”

Comparison of Intensive Chemotherapy and Hypomethylating Agents before Allogeneic Stem Cell Transplantation for Advanced Myelodysplastic Syndromes: A Study of the Myelodysplastic Syndrome Subcommittee of the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplant Research

“…This potentially explains the equivalent outcomes in the HMA and CC groups despite the higher proportion of patients not in CR in the HMA group at the time of HSCT. A recent publication by a French group demon-strated no difference in post-HSCT outcomes when AZA was compared with the best supportive care before HSCT [20]. Furthermore, given evidence that a number of patients potentially suitable for transplantation submitted to prein-duction therapy do not reach transplantation [21], it may be that an upfront HCST approach is preferable for selected patients.…”

Transplant for MDS: Challenges and emerging strategies

“…The same group also compared the use of azacitidine alone to induction chemotherapy or azacitidine preceded or followed by induction chemotherapy in patients who received MAC or RIC allo-HSCT from MRD or MUD and showed no difference in OS, DFS, relapse and NRM among patients treated with either azacitidine or induction chemotherapy. However, patients who received azacitidine and induction chemotherapy had significantly lower OS, DFS and higher NRM compared to patients who received only azacitidine or induction chemotherapy [44].…”