Therapeutic Challenges and Emerging Strategies for T674I and PTPN11 Mutations in a FIP1L1-PDGFRA-Positive Myeloproliferative Neoplasm: A Case Report

Myeloproliferative neoplasm (MPN) with eosinophilia associated with <i>FIP1L1-PDGFRA</i> is a rare eosinophilic disorder typically treated with imatinib. However, resistance due to the T674I mutation poses a significant challenge. This case presents the first reported instance of concurrent <i>FIP1L1-PDGFRA T674I</i> and <i>PTPN11</i> (p.E76D) mutations in a 38-year-old male patient with MPN and eosinophilia. The patient initially responded to imatinib but developed resistance after ten months, leading to severe spinal cord compression caused by granulocytic sarcoma. Despite undergoing radiotherapy, chemotherapy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT), the disease progressed. Although full donor chimerism was achieved post-transplant, the patient relapsed shortly afterward with eosinophilia, splenomegaly, and constitutional symptoms. Further treatments, including sorafenib and decitabine, failed to control the disease, and the patient ultimately died from multiorgan failure. This case illustrates the therapeutic challenges associated with <i>FIP1L1-PDGFRA T674I</i>-positive eosinophilic disorder, especially when compounded by the <i>PTPN11</i> mutation. Resistance to standard treatments underscores the urgent need for novel therapies to manage this rare and aggressive disease.