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.

Figure 1.

Therapeutic algorithm for adult patients with MDS and (very) low-risk or intermediate IPSS-R risk scores. ^@ indicates nonfit (patients with multiple comorbidities and/or poor performance) or fit (patients with no comorbidities and good performance status). * indicates nontransplant strategies according to most recent versions published by international MDS expert groups, including ELN and NCCN. & indicates failure of nontransplant strategies (for details of various nontransplant interventions [transfusions, ESAs, lenalidomide, and cytoreductive therapy], see “Timing of transplantation.” Nontransplant interventions may include >1 line of nontransplant intervention, eg, treatment with ESAs, followed by lenalidomide in patients with 5q−). ** indicates poor-risk features (defined as poor-risk cytogenetic characteristics, persistent blast increase [>50% or with >15% BM blasts], life-threatening cytopenias [neutrophil counts, <0.3 × 10⁹/L; platelet counts, <30 × 10⁹/L], high transfusion intensity ≥2 units per months for 6 months; molecular testing should be seriously considered, in case of absence of poor-risk cytogenetic characteristics or persistent blast increase). # indicates transplant strategies (all forms of HSCT, for details of donor selection, type of conditioning and posttransplant strategies, see text; no upper age limit if patients are fit, without serious comorbidity and good Karnofsky status). @ indicates donor availability (the improved outcome of HSCT with haploidentical donors utilizing posttransplant cyclophosphamide increases the donor availability).

Figure 2.

Therapeutic algorithm for adult patients with MDS and poor IPSS-R scores. ^@ indicates nonfit (patients with multiple comorbidities and/or poor performance) or fit (patients with no comorbidities and good performance status). * indicates nontransplant strategies according to most recent versions published by international MDS expert groups, including ELN and NCCN. & indicates failure of nontransplant strategies (for details of various nontransplant interventions [transfusions, ESAs, lenalidomide and cytoreductive therapy], see “Timing of transplantation.” Nontransplant interventions may include >1 line of nontransplant intervention, eg, treatment with ESAs, followed by lenalidomide in patients with 5q−). ** indicates poor-risk features (defined as poor-risk cytogenetic characteristics, persistent blast increase [>50% or with >15% BM blasts], life-threatening cytopenias [neutrophil counts, <0.3 × 10⁹/L; platelet counts, <30 × 10⁹/L], high transfusion intensity ≥2 units per months for 6 months; molecular testing should be seriously considered, in case of absence of poor-risk cytogenetic characteristics or persistent blast increase). # indicates transplant strategies (all forms of HSCT, for details of donor selection, type of conditioning and posttransplant strategies, see text; no upper age limit if patients are fit, without serious comorbidity and good Karnofsky status). ^@ indicates donor availability (the improved outcome of HSCT with haploidentical donors utilizing posttransplant cyclophosphamide increases the donor availability).