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.

In this multicenter retrospective study, the long-term outcomes of 878 adults with AML and refractory anemia with excess blasts (RAEB) with BM blasts <10% who underwent transplantation with an HLA-identical sibling donor between 1998 and 2004 were analyzed according to four regimens of conditioning intensity: reduced-intensity conditioning (RIC) (either intermediate RIC (IntermRIC) or non-myeloablative (NMA) RIC), and myeloablative conditioning (MC) in 718 patients (either conventional MC or hyperintense MC. In multivariate cox analysis, patients undergoing NMA transplantation had lower non-relapse mortality risk in the first 100 days after transplantation (P<0.01), but a higher risk beyond day +100 (P=0.02), as well as higher relapse incidence in the first 12 months (P<0.01), but the risk was similar in all groups beyond 12 months. The probabilities of PFS and OS up to 7 years were significantly lower only in the NMA subgroup (P0.01 for both). The 7-year OS was 53%, 29%, 56% and 51%, respectively. Our data suggest that prospective studies comparing RIC regimens (especially IntermRIC) with MC are appropriate in patients with AML and RAEB who are in a non-advanced disease status.

The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLA-matched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P ≤ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P ≤ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (≤18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.

Post-transplant cyclophosphamide (PTCy) has become a promising option after allo-SCT, but infections may be more common than in traditional protocols. We herein report 117 consecutive adults who received PTCy-based alloSCT in our hospital: HaploSCT (34%), MRD (19%), and VUD (47%), respectively. The 18-month incidence of severe bacterial, viral, and IFI was 56%, 69%, and 8.7%, without differences between donor type, except for CMV infection and viral hemorrhagic cystitis, which had a higher incidence in the haploSCT cohort (58% vs. 43% and 30% vs. 8% on day +90, p < 0.05). Late infections by conventional respiratory viruses were common in all groups [33/87 (38%)]. The 2-year survival was 72% and did not differ by donor type. IRM at day 30, day 100, and 18 months was 1.7%, 4.4%, and 12%, without differences by donor type (p = 0.7). The primary cause of IRM was bacterial infection (42%). Grade 2–4 acute GvHD was the only independent predictor of IRM. Donor type had no impact on IRM or on survival. In our study, severe infections were common in all donor types using PTCy, with higher rates of early post-engraftment CMV-I and viral HC in haploSCT recipients, although lethal infections were uncommon and similar in all donor types.