Allogeneic hematopoietic stem cell transplantation in Philadelphia-negative adult ALL: myeloablative, non-myeloablative, and beyond

Abstract

Objectives: Myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a matched sibling donor (MSD) in first complete remission (CR1) is an effective consolidation for adult acute lymphoblastic leukemia (ALL), and matched unrelated donor (MUD) is an alternative stem cell source.

Methods: Based on a search of the English literature for MUD transplant in Philadelphia-negative ALL, this review first compares the treatment outcomes of myeloablative allo-HSCT with MUD and MSD, followed by a mini-review of studies of non-myeloablative, reduced intensity conditioning (RIC) allo-HSCT in ALL, and finally measures to improve outcome of MUD allo-HSCT.

Results: Publications are inevitably confounded by inclusion of Philadelphia-positive cases, patients beyond CR1, and mismatched unrelated donors in addition to heterogeneity in the length of follow-up. Despite these limitations, the overall data showed that MUD allo-HSCT resulted in comparable survivals with matched related donor (MRD) transplant. Moreover, Asian studies reported a lower transplant-related mortality (TRM) than Western studies. As graft failure is infrequent even in the MUD setting, acute graft versus host disease (aGVHD) remains a major cause of TRM. In addition, RIC allo-HSCT produced promising long-term disease-free survival (DFS) with a low TRM in adult ALL if transplanted in CR1.

Discussion: Potential ways to reduce TRM further include antifungal prophylaxis and optimal management of life-threatening non-infective interstitial pneumonitis. Moreover, harnessing graft-versus-leukemia effect with hypomethylating agents warrants clinical trial.

Conclusion: Myeloablative MUD allo-HSCT resulted in comparable survivals with MRD transplant. RIC allo-HSCT produced promising long-term DFS with a low TRM in adult ALL.

Keywords: Acute lymphoblastic leukemia; Allogeneic; Matched unrelated donor; Myeloablative; Reduced intensity conditioning.