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

## TL;DR

This paper reviews the changing role of allogeneic hematopoietic cell transplantation in treating Ph-negative B-cell ALL, emphasizing the impact of MRD testing and new therapies.

## Contribution

The paper provides updated insights into the evolving role of allo-HCT and novel therapies in Ph-negative B-ALL based on MRD status.

## Key findings

- Allo-HCT is strongly recommended for high-risk Ph-negative ALL patients who are MRD positive after induction.
- New therapies like blinatumomab and CAR T-cell therapy show promise in reducing relapse and improving safety.
- MRD status is becoming a key factor in determining the need for allo-HCT in standard-risk patients.

## Abstract

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.