Journal: American journal of hematology
This review article examines how modern targeted and immunotherapies are reshaping the role of allogeneic hematopoietic cell transplantation (HCT) in adults with Philadelphia chromosome–positive acute lymphoblastic leukemia.
Key points:
- Prognosis has improved dramatically over the last 20 years with sequential use of BCR::ABL1 tyrosine kinase inhibitors (TKIs)—imatinib, then dasatinib, and more recently ponatinib—leading to deeper and more durable molecular responses.
- Incorporation of immunotherapy, especially blinatumomab, has enabled chemotherapy-sparing frontline regimens that can be both more effective and better tolerated.
- Transplant decisions are now individualized, challenging the previous standard that essentially all patients should undergo allogeneic HCT in first complete remission.
- Measurable residual disease (MRD) drives risk stratification:
- Patients achieving early, deep, and sustained MRD negativity with potent TKIs and immunotherapy may be able to avoid transplant, although long-term outcome data are still limited.
- Those with persistent or recurrent MRD, or higher-risk clinical/biologic features, remain candidates for HCT.
- Outcomes for patients who proceed to HCT depend heavily on transplant-related variables, including donor choice, conditioning intensity, graft-versus-host disease prophylaxis, and the use of post-transplant TKI maintenance to enhance graft-versus-leukemia effect while controlling toxicity.
- Emerging directions include:
- Treatment-free remission after prolonged TKI therapy in non-transplant patients.
- Roles for CD19-directed CAR T-cell therapy as a bridge to HCT, as consolidation, or as salvage.
Overall, the article provides a contemporary framework for deciding when allogeneic HCT is indicated in this disease, integrating MRD status, TKI generation, depth and duration of molecular response, and individual patient factors.