From MRD To Match: the Role of Allogeneic Hematopoietic Cell Transplant in Philadelphia-Negative B-ALL

Given the high risk of relapse for Philadelphia-negative (Ph-negative) B-cell acute lymphoblastic leukemia (ALL), allogeneic hematopoietic cell transplantation (allo-HCT) is often recommended following first complete remission (CR1) in high-risk patients. However, in the era of measurable residual disease (MRD) testing, allo-HCT may not be indicated for patients with standard-risk disease. Here we review the use of allo-HCT and other consolidative approaches for standard- and high-risk Ph-negative ALL, based on MRD following induction therapy.

Allo-HCT is strongly indicated for patients with high-risk Ph-negative ALL, especially those who are MRD positive at end of induction. Ongoing trials using cellular and immune therapies such as blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor (CAR) T-cell therapies have shown promising results in deepening response and decreasing relapse. Further, these agents have demonstrated overall manageable safety profiles.

The role for allo-HCT following CR1 in patients with standard risk Ph-negative ALL is evolving with advances in therapeutic approaches. MRD is emerging as a critical prognostic factor regardless of treatment strategy, thus questioning the necessity of transplant in MRD-negative patients. With the advances in safety and accessibility of allo-HCT as well as novel therapeutics, overall outcomes in ALL continue to improve.