Philadelphia chromosome-positive acute myeloid leukemia (Ph+AML) is a rare and aggressive subtype of AML, characterized by the BCR::ABL1 fusion gene. It has historically been considered a high-risk leukemia, with allogeneic Hematopoietic Cell Transplant (HCT) recommended in the first remission. However, the emergence of targeted therapies, particularly potent Tyrosine Kinase Inhibitors (TKIs), has led to reconsideration of this approach. Drawing from advances in Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL), where HCT omission has been explored successfully, this study examines whether a similar strategy can be applied in select Ph+AML cases.

To evaluate the feasibility of a non-HCT approach in Ph+AML by analyzing a case where transplant was omitted, and the patient achieved sustained remission.

We present a case of a 30-year-old male diagnosed with de novo Ph+AML, identified through cytogenetics and molecular testing. The patient received induction chemotherapy with cytarabine and anthracycline (3+7) along with a TKI. Due to complications, his initial TKI was switched to ponatinib, and consolidation therapy consisted of azacytidine, venetoclax, and ponatinib. Disease monitoring was performed using quantitative Polymerase Chain Reaction (qPCR) for BCR::ABL1 and Next-Generation Sequencing (NGS).

The patient achieved a complete Molecular Response (MR 4.5) after the first cycle of consolidation therapy. Over 12-cycles of treatment, he maintained MRD negativity without emerging mutations. At 30-months post-diagnosis, he remains in sustained remission without undergoing HCT. Key factors that may have contributed to his favorable outcome include the absence of additional cytogenetic abnormalities, early achievement of deep molecular remission, and the use of a third generation TKI with activity against T315I mutations.

This case suggests that a transplant-free approach may be a viable option for select patients with Ph+AML. While HCT remains the standard of care, the use of targeted therapies such as ponatinib in combination with venetoclax and azacytidine may provide an alternative pathway to long-term remission. Further studies are needed to validate patient selection criteria and assess long-term efficacy and safety of this approach.