Haploidentical Stem Cell Transplantation for Acute Myeloid Leukemia: Current Therapies, Challenges and Future Prospective

Abstract

Haploidentical stem cell transplantation (haplo-SCT), an alternative donor source, offers a curative therapy for patients with acute myeloid leukemia (AML) who are transplant candidates. Advances in transplantation techniques, such as donor selection, conditioning regimen modification, and graft-versus-host disease prophylaxis, have successfully improved the outcomes of AML patients receiving haplo-SCT and extended the haploidentical transplant indictions for AML. Presently, treating de novo AML, secondary AML, therapy-related AML and refractory and relapsed AML with haplo-SCT can achieve comparable outcomes to those of human leukocyte antigen (HLA)-matched sibling donor transplantation (MSDT), unrelated donor transplantation or umbilical cord blood transplantation. For some subgroups of AML subjects, such as patients with positive pretransplantation minimal/measurable residual disease, recent studies suggest that haplo-SCT might be superior to MSDT in decreasing relapse and improving survival. Unfortunately, for patients with AML after haplo-SCT, relapse and infections remain the causes of death that restrict further improvement in clinical outcomes. In this review, we discuss the recent advances and challenges in haplo-SCT for AML treatment, mainly focusing on unmanipulated haplo-SCT protocols. We provide an outlook on future prospects and suggest that relapse prophylaxis, intervention, and treatment, as well as infection prevention and therapy, are areas of active research in AML patients who receive haploidentical allografts.

Human leukocyte antigen‐haploidentical transplantation for relapsed/refractory acute myeloid leukemia: Better leukemia‐free survival with bone marrow than with peripheral blood stem cells in patients ≥55 years of age

“…25 Haplo-HCT is increasingly used in patients with active AML at transplantation. 27 While PTCy is highly efficient at preventing GVHD it also has a strong impact on immune reconstitution after transplantation by rendering alloreactive T-cells functionally impaired. 28,29 It is thus unclear whether observations made by prior studies comparing BM to PBSC on GVL effects outside of the PTCy setting hold true in the PTCy-based Haplo-HCT setting.…”

“…Haplo‐HCT is increasingly used in patients with active AML at transplantation 27 . While PTCy is highly efficient at preventing GVHD it also has a strong impact on immune reconstitution after transplantation by rendering alloreactive T‐cells functionally impaired 28,29 .…”

Trends in disease indications for hematopoietic stem cell transplantation in the Asia-Pacific region: A report of the Activity Survey 2017 from APBMT

“…Compared to unrelated transplants, we found a remarkable increase in the number of related transplants for patients with AML, which reflected the increasing number of haploidentical transplants. In particular, Chang et al reported that haploidentical allogeneic transplants for AML were the most attractive alternative donors because almost every patient can find a donor in China 20 . Our survey results also reflected this continued growth in transplant activity, in which a significant number of patients with AML were treated with haploidentical transplants in China 11 .…”

Successful haploidentical stem cell transplantation for therapy‐related acute myeloid leukemia after autologous transplantation of Hodgkin lymphoma

“…The induction chemotherapy used Cytarabine 100 mg/m 2 and Mitoxantrone 12 mg/m 2 followed by Cytarabine 1000 mg/m 2 for consolidation, and complete remission was achieved with negative measurable residual disease. Due to poor outcome of tAML, he received haploidentical HSCT (haplo‐HSCT) with myeloablative conditioning regimens followed by post‐transplant cyclophosphamide in December 2021 with donor cells from his daughter due to no matched donor available 5 . On post‐HSCT day 30, bone morrow examination revealed engraftment of donor stem cells with full donor chimerism.…”

“…However, availability of stem cells is time‐consuming and experience is limited. HSCT with haploidentical source, which is easily available, 5 is another option for such a dilemma. We report a rare and successful haplo‐HSCT for tAML after 10 years of auto‐HSCT of Hodgkin lymphoma and suggest the value of haplo‐HSCT in such condition.…”