Transplant in ALL: who, when, and how?

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a cornerstone in the treatment of high-risk acute lymphoblastic leukemia (ALL), yet optimal patient selection is challenging in the era of rapidly changing modern therapy. Refined molecular characterization allows for better risk assessment, sparing low-risk patients from allo-HCT toxicity while identifying those who may benefit from intensified approaches. Measurable residual disease (MRD) has emerged as a powerful predictor of relapse irrespective of treatment strategy, challenging the necessity of transplant in MRD-negative patients. Further, expanded donor options, particularly haploidentical transplantation coupled with reduced intensity conditioning, have extended the applicability of allo-HCT to a broader range of patients. Finally, immunotherapies and targeted treatments are increasingly integrated into both initial and relapsed treatment protocols yielding deep remission and allowing for successful transplant in patients with a history of advanced disease. In this review, we provide an overview of the contemporary role of transplant in adult patients with ALL, focusing on indications for allo-HCT in first remission, optimal sequencing of transplant with novel therapies, and advancements in donor selection and conditioning regimens.

Graphical abstract

Figure 1.

Commonly used myeloablative and reduced intensity conditioning regimens in acute lymphoblastic leukemia in the US, 2019–2022. MAC, myeloablative conditioning; RIC/NMA, reduced intensity conditioning/non-myeloablative regimen; Bu, busulfan; Cy, cyclophosphamide; Flu, fludarabine; Mel, melphalan; TBI, total body irradiation.

Figure 2.

Relative proportion of allo-HCT by donor types in the US by recipient age, 2019-2022. Haplo, ≥2 HLA antigen mismatch; MMUD, mismatched unrelated donor ≤7/8 HLA allele match; MRD, matched relate donor; MUD, matched unrelated donor; UCB, umbilical cord blood.