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Review
. 2021 May 3:12:659595.
doi: 10.3389/fimmu.2021.659595. eCollection 2021.

Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia: Who, When, and How?

Justin Loke  1   2 , Richard Buka  1   2 , Charles Craddock  1   2
Affiliations
Review

Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia: Who, When, and How?

Justin Loke et al. Front Immunol. .

Abstract

Although the majority of patients with acute myeloid leukemia (AML) treated with intensive chemotherapy achieve a complete remission (CR), many are destined to relapse if treated with intensive chemotherapy alone. Allogeneic stem cell transplant (allo-SCT) represents a pivotally important treatment strategy in fit adults with AML because of its augmented anti-leukemic activity consequent upon dose intensification and the genesis of a potent graft-versus-leukemia effect. Increased donor availability coupled with the advent of reduced intensity conditioning (RIC) regimens has dramatically increased transplant access and consequently allo-SCT is now a key component of the treatment algorithm in both patients with AML in first CR (CR1) and advanced disease. Although transplant related mortality has fallen steadily over recent decades there has been no real progress in reducing the risk of disease relapse which remains the major cause of transplant failure and represents a major area of unmet need. A number of therapeutic approaches with the potential to reduce disease relapse, including advances in induction chemotherapy, the development of novel conditioning regimens and the emergence of the concept of post-transplant maintenance, are currently under development. Furthermore, the use of genetics and measurable residual disease technology in disease assessment has improved the identification of patients who are likely to benefit from an allo-SCT which now represents an increasingly personalized therapy. Future progress in optimizing transplant outcome will be dependent on the successful delivery by the international transplant community of randomized prospective clinical trials which permit examination of current and future transplant therapies with the same degree of rigor as is routinely adopted for non-transplant therapies.

Keywords: acute myeloid leukemia; allogeneic stem cell transplantation; chemotherapy; graft-versus-leukemia; measurable residual disease (MRD); minimal residual disease.

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Conflict of interest statement

CC has received honoraria from Celgene, Daichi-Sankyo, Novartis and Pfizer as well as research funding from Celgene. JL has received travel funding from Novartis and Daichi-Sankyo, honoraria from Pfizer, Janssen and Amgen. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer CS has declared past co-authorships with one of the authors CC, to the handling editor, at the time of review.

Figures

Figure 1
Figure 1
Identifying patients with Acute Myeloid Leukemia (AML) who are likely to benefit from allogeneic stem cell transplantation (allo-SCT). MRD, Measurable Residual Disease; TRM, Transplant related mortality; HCT-CI, Hematopoietic cell transplantation - specific comorbidity index; NGS, next generation sequencing.
Figure 2
Figure 2
Role of measurable residual disease (MRD) and novel agents at different stages of the treatment pathway in acute myeloid leukemia (AML). GVHD, graft versus host disease; DLI, donor lymphocyte infusion.
Figure 3
Figure 3
Risk-benefit analysis for maintenance therapy post-allogeneic stem cell transplant. MRD, measurable residual disease; GVHD, graft versus host disease.
See this image and copyright information in PMC

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