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Although further evidence for a graft-versus-leukemia effect by DLI is provided, our results confirm, that the clinical benefit is limited to a minority of patients. Strategies to reduce tumor burden before DLI, as well as alternative treatment options should be investigated in adults with relapsed AML after HSCT.

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.

Previous randomized graft-versus-host disease (GVHD)-prophylaxis trials have failed to demonstrate reduced incidence and severity of chronic GVHD (cGVHD).Here we reanalyzed and updated a randomized phase 3 trial comparing standard GVHD prophylaxis with or without pretransplantation ATG-Fresenius (ATG-F) in 201 adult patients receiving myeloablative conditioning before transplantation from unrelated donors. The cumulative incidence of extensive cGVHD after 3 years was 12.2% in the ATG-F group versus 45.0% in the control group (P < .0001). The 3-year cumulative incidence of relapse and of nonrelapse mortality was 32.6% and 19.4% in the ATG-F group and 28.2% and 33.5% in the control group (hazard ratio [HR] ‫؍‬ 1.21, P ‫؍‬ .47, and HR ‫؍‬ 0.68, P ‫؍‬ .18), respectively. This nonsignificant reduction in nonrelapse mortality without increased relapse risk led to an overall survival rate after 3 years of 55.2% in the ATG-F group and 43.3% in the control group (HR ‫؍‬ 0.84, P ‫؍‬ .39, nonsignificant). The HR for receiving immunosuppressive therapy (IST) was 0.31 after ATG-F (P < .0001), and the 3-year probability of survival free of IST was 52.9% and 16.9% in the ATG-F versus control, respectively. The addition of ATG-F to standard cyclosporine, methotrexate GVHD prophylaxis lowers the incidence and severity of cGVHD, and the risk of receiving IST without raising the relapse rate. ATG-F prophylaxis reduces cGVHD morbidity. (Blood. 2011; 117(23):6375-6382) IntroductionAllogeneic hematopoietic stem cell transplantation (HSCT) is increasingly used worldwide as a curative therapy for malignant and nonmalignant hematologic disorders. Chronic graft-versushost disease (cGVHD) is the leading cause of nontransplantation mortality and morbidity after allogeneic HSCT. 1-3 cGVHD is a multiorgan disease resembling autoimmune disorders, such as scleroderma or systemic lupus. 4,5 Its incidence and prevalence are rising because of transplantation practices known to be associated with increased risk of cGVHD. 4,6 Indeed, older patients now undergo HSCT, and more transplantations are being performed from unrelated donors and/or with peripheral blood stem cells instead of bone marrow. Furthermore, the reduced-intensity conditioning (RIC) regimens developed during recent years have also led to higher numbers of transplantations performed worldwide. 7,8 However, although the acute GVHD (aGVHD) rate appears lower after RIC, the incidence of cGVHD seems to be unaffected. 9 Altogether, cGVHD thus remains the most challenging complication after allogeneic HSCT. 10 The main risk factor for developing cGVHD is the previous occurrence of aGVHD. 11 Thus, transplantation physicians have focused on decreasing the rate of aGVHD to lower nonrelapse mortality (NRM) associated with both aGVHD and cGVHD. However, although calcineurin inhibitors (cyclosporine or tacrolimus) in association with methotrexate have proven to decrease the aGVHD rate in randomized studies and although new regimens, such as the association of rapamycin with tacrolimus, seem to l...

FLT3/ITD adversely affected the outcome of HSCT in the same direction it does after chemotherapy; despite this, more than half of the patients harboring this mutation who received transplants were alive and leukemia free at 2 years. To further improve the results, use of FLT3 inhibitors before or after HSCT deserves investigation.