Case Report: The diagnostic and therapeutic crossroads: when myelofibrosis transforms into mixed phenotype acute leukemia

Background: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by the proliferation of fibrous tissue in the bone marrow. Transformation to acute leukemia, typically acute myeloid leukemia, represents a terminal event in its natural history; however, transformation to mixed phenotype acute leukemia (MPAL) is exceedingly rare. The diagnosis and treatment of MPAL are particularly challenging, especially in elderly patients with underlying MF. The clinical characteristics, treatment response, and prognosis of such cases remain unclear and are rarely reported. Case presentation: mutations. A definitive diagnosis of MPAL (T/Myeloid mixed phenotype) transformed from PMF was established. Given the patient's advanced age and underlying MF, two cycles of a low-intensity chemotherapy regimen primarily based on the "VP regimen (Vincristine + Prednisone) combined with Azacitidine" were administered. Initial treatment resulted in a complete remission with incomplete hematologic recovery (CRi). Considering the incomplete recovery of peripheral blood platelets and the presence of minimal residual blasts detected by bone marrow flow cytometry, the patient was started on a regimen combining the VP regimen with a VA regimen chemotherapy to achieve a deep and durable complete remission. As of the latest follow-up, the patient's relevant laboratory results remain within a safe range, with no peripheral blasts detected. Her psychological and physiological status is acceptable, she reports no specific discomfort, and her disease is well-controlled. Discussion: ), providing a concrete example for understanding the genetic mechanisms underlying such transformations. 3) Treatment Dilemma in the Elderly: The case highlights the immense therapeutic challenges in elderly MPAL patients with concomitant persistent myelofibrosis. While low-intensity regimens may induce short-term remission, the responses are not durable. Patient tolerability to intensive chemotherapy and novel targeted agents (e.g., Venetoclax) is poor, leading to a dismal prognosis. 4) Management Implications: It emphasizes the necessity of long-term, regular follow-up and early intervention for MF patients, particularly those harboring high-risk mutations. Furthermore, it underscores the urgent need for more effective and better-tolerated novel therapies for this patient population. Conclusion: -positive PMF. This case not only serves as a unique model illustrating the complex evolution of a malignant clone but also profoundly reveals the unique therapeutic challenges and extremely poor survival outcome resulting from the convergence of advanced age, MF background, and MPAL transformation. It offers pivotal real-world evidence for the clinical management of this specific patient population and highlights the need to explore novel therapeutic strategies.