Debate: Should patients with Ph− ALL who reach MRD-negativity receive allo-HSCT?

Over the past 20 years, the prognosis of Philadelphia chromosome-negative (Ph−) B-cell or T-cell acute lymphoblastic leukemia (ALL) has significantly improved with the introduction of intensive chemotherapy protocols and targeted therapies such as immunotoxins, T-cell bispecific engagers, and chimeric antigen receptor T-cell therapies. The use of allogeneic hematopoietic stem cell transplantation is widely debated in patients with Ph− ALL, as these patients can now be effectively treated without this highly toxic procedure.

Here, we present a debate by Chevallier.¹ and Boissel.² published in The Lancet Hematology on whether patients with Ph− ALL who reach measurable residual disease (MRD) negativity should receive allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Key points

• Allo-HSCT is indicated in patients at a high risk of relapse, defined as a high level of MRD or MRD positivity.
• Allo-HSCT is indicated for adult patients in first line therapy and in pediatric patients in both first-line and second-line therapies¹; however, the role of transplant in older patients and those with relapsed/refractory disease who are MRD-negative is largely debated.¹ The authors opinion on this debate are presented in Figure 1.

ALL, acute lymphoblastic leukemia; allo-HSCT, allogeneic hematopoietic stem cell transplantation; MRC, Medical Research Council; MRD, measurable residual disease; OS, overall survival; PCR, polymerase chain reaction; R/R, relapsed/refractory; WBC, white blood count.
*Adapted from Chevallier.¹ and Boissel.²

Key learnings
Allo-HSCT is a feasible option for younger adults with Ph− ALL who reach MRD-negativity, but it should not be the only criteria guiding transplant indication. For older patients with Ph− ALL, the use of early blast clearance or other baseline high-risk features should be considered to indicate HSCT when MRD monitoring is not available.