Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML.

Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P = .01; HR, 1.71; P < .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P = .002, and HR, 1.47; P < .001), as was overall survival (HR, 1.32; P < .001, and HR, 1.45; P < .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.

Hematopoietic Cell Transplantation in the Treatment of Newly Diagnosed Adult Acute Myeloid Leukemia: An Evidence-Based Review from the American Society of Transplantation and Cellular Therapy.

The role of hematopoietic cell transplantation (HCT) in the management of newly diagnosed adult acute myeloid leukemia (AML) is reviewed and critically evaluated in this evidence-based review. An AML expert panel, consisting of both transplant and nontransplant experts, was invited to develop clinically relevant frequently asked questions covering disease- and HCT-related topics. A systematic literature review was conducted to generate core recommendations that were graded based on the quality and strength of underlying evidence based on the standardized criteria established by the American Society of Transplantation and Cellular Therapy Steering Committee for evidence-based reviews. Allogeneic HCT offers a survival benefit in patients with intermediate- and high-risk AML and is currently a part of standard clinical care. We recommend the preferential use of myeloablative conditioning in eligible patients. A haploidentical related donor marrow graft is preferred over a cord blood unit in the absence of a fully HLA-matched donor. The evolving role of allogeneic HCT in the context of measurable residual disease monitoring and recent therapeutic advances in AML with regards to maintenance therapy after HCT are also discussed.

Haploidentical Donors: Can Faster Transplantation Be Life-Saving for Patients with Advanced Disease?

Haploidentical stem cell transplantation is a therapeutic option for patients without an HLA-matched donor. It is increasingly being used worldwide due to the application of posttransplantation cyclophosphamide and is associated with lower incidence of graft-versus-host disease and treatment-related mortality. Haploidentical donors are generally available for most patients and stem cells can be rapidly obtained. Delays in transplantation while waiting for unrelated donor cells can be potentially problematic for patients with advanced disease at risk for progression; thus, the use of haploidentical donors, especially in this setting, can be life-saving. Here we reviewed the literature on haploidentical stem cell transplantation performed with posttransplantation cyclophosphamide.

Advances in haploidentical stem cell transplantation

Hematopoietic stem cell transplantation from haploidentical donors is an attractive method of transplantation due to the immediate donor availability, ease of stem cell procurement and the possibility to collect additional donor cells for cellular therapy, if needed. Historically, maintaining T-cells in the graft has been associated with very high rates of graft-versus-host disease, while T-cell depleted haploidentical transplantation has been limited by a higher incidence of graft rejection and delayed immune reconstitution post-transplant. Recent approaches attempt to maintain the T-cells in the graft while effectively preventing the development of graft-versus-host disease post-transplant. Selective depletion of alloreactive T-cells post-transplant using high-dose post-transplant cyclophosphamide is under investigation as a promising alternative in haploidentical transplantation. While engraftment has improved and graft-versus-host disease is controlled with this approach, future directions should focus on optimizing conditioning regimens and the prevention of disease relapse post-transplant.

Advances in haploidentical stem cell transplantation.

Hematopoietic stem cell transplantation from haploidentical donors is an attractive method of transplantation due to the immediate donor availability, ease of stem cell procurement and the possibility to collect additional donor cells for cellular therapy, if needed. Historically, maintaining T-cells in the graft has been associated with very high rates of graft-versus-host disease, while T-cell depleted haploidentical transplantation has been limited by a higher incidence of graft rejection and delayed immune reconstitution post-transplant. Recent approaches attempt to maintain the T-cells in the graft while effectively preventing the development of graft-versus-host disease post-transplant. Selective depletion of alloreactive T-cells post-transplant using high-dose post-transplant cyclophosphamide is under investigation as a promising alternative in haploidentical transplantation. While engraftment has improved and graft-versus-host disease is controlled with this approach, future directions should focus on optimizing conditioning regimens and the prevention of disease relapse post-transplant.