Background: Tyrosine kinase inhibitors (TKIs) represent the standard of care for chronic myeloid leukemia (CML). Although cytopenias are frequent, severe and persistent bone marrow aplasia is exceedingly rare, with limited evidence to guide management in non-transplant candidates. Case presentation: A 35-year-old man with chronic-phase CML developed persistent bone marrow aplasia after sequential treatment with imatinib and dasatinib. Despite dose reductions and supportive measures, profound pancytopenia persisted, leading to treatment cessation. In the absence of a matched donor and response ( BCR::ABL1 : 25% IS), ponatinib was initiated at 45 mg daily and later reduced to 15 mg. Remarkably, hematologic recovery occurred, with normalization of peripheral blood counts, without recurrence of aplasia, and the patient achieved a sustained complete cytogenetic response within 15 months ( BCR::ABL1 < 1% IS). Discussion: TKI-associated bone marrow aplasia has been reported with agents such as imatinib, dasatinib, and nilotinib. Proposed mechanisms include off-target inhibition of hematopoietic kinases (eg, c-KIT, PDGFR) and suppression of malignant clones preceding normal marrow recovery. Management typically involves discontinuation, transfusion support, immunosuppressive therapy, or transplantation. In this case, ponatinib proved effective and tolerable as salvage therapy after previous TKI-induced marrow aplasia. Conclusion: TKI-induced bone marrow aplasia is an uncommon but serious toxicity in CML. This case supports the potential role of ponatinib as an effective salvage option following severe TKI-related marrow toxicity, particularly in patients who are not candidates for allogeneic transplantation. Further clinical experience and larger studies are needed to better define optimal management strategies for this rare but serious complication.
Ghasoub et al. (Sun,) studied this question.