Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel

Abstract

An international expert panel, active within the European Society for Blood and Marrow Transplantation, European LeukemiaNet, Blood and Marrow Transplant Clinical Trial Group, and the International Myelodysplastic Syndromes Foundation developed recommendations for allogeneic hematopoietic stem cell transplantation (HSCT) in myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). Disease risks scored according to the revised International Prognostic Scoring System (IPSS-R) and presence of comorbidity graded according to the HCT Comorbidity Index (HCT-CI) were recognized as relevant clinical variables for HSCT eligibility. Fit patients with higher-risk IPSS-R and those with lower-risk IPSS-R with poor-risk genetic features, profound cytopenias, and high transfusion burden are candidates for HSCT. Patients with a very high MDS transplantation risk score, based on combination of advanced age, high HCT-CI, very poor-risk cytogenetic and molecular features, and high IPSS-R score have a low chance of cure with standard HSCT and consideration should be given to treating these patients in investigational studies. Cytoreductive therapy prior to HSCT is advised for patients with ≥10% bone marrow myeloblasts. Evidence from prospective randomized clinical trials does not provide support for specific recommendations on the optimal high intensity conditioning regimen. For patients with contraindications to high-intensity preparative regimens, reduced intensity conditioning should be considered. Optimal timing of HSCT requires careful evaluation of the available effective nontransplant strategies. Prophylactic donor lymphocyte infusion (DLI) strategies are recommended in patients at high risk of relapse after HSCT. Immune modulation by DLI strategies or second HSCT is advised if relapse occurs beyond 6 months after HSCT.

Hypomethylating agents for treatment and prevention of relapse after allogeneic blood stem cell transplantation

“…Results from the retrospective reports and the limited number of prospective trials have established HMA and in particular Aza as a valuable treatment alternative for patients who relapse after allo-SCT [32,33]. Still, several questions regarding the practical use of HMA as salvage therapy after transplant have not been answered sufficiently yet.…”

“…Therefore, this approach has been incorporated as a treatment option for these patients in the current recommendations of the EBMT and the European Leukemia Net [32,33].…”

CMML: Clinical and molecular aspects

“…There is to date no retrospective study to delineate the best timing for ASCT in CMML, but experts recommend to proceed to transplant in eligible patients with intermediate-2 or high CPSS risk [67]. Patients with blasts >10% likely benefit from some form of treatment prior to transplant, and this increasingly relies on HMA.…”

Haploidentical transplant in patients with myelodysplastic syndrome

“…1,2 Less than 30% of these patients will have an HLA-matched sibling donor available. For patients lacking an HLAmatched sibling donor, an HLA-matched unrelated donor can be recruited in .50% of patients, but this is strongly dependent on the ethnic background, because most of the volunteer donors are of Caucasian origin.…”