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

## TL;DR

This case report describes a rare and aggressive myeloproliferative neoplasm with resistance to standard treatments due to specific mutations.

## Contribution

The first reported case of concurrent FIP1L1-PDGFRA T674I and PTPN11 mutations in a myeloproliferative neoplasm.

## Key findings

- The patient initially responded to imatinib but developed resistance after ten months.
- Despite multiple treatments, including allo-HSCT, the disease progressed and the patient died from multiorgan failure.
- The case highlights the challenges of treating FIP1L1-PDGFRA T674I-positive disease with PTPN11 mutation.

## Abstract

Myeloproliferative neoplasm (MPN) with eosinophilia associated with FIP1L1-PDGFRA 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 FIP1L1-PDGFRA T674I and PTPN11 (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 FIP1L1-PDGFRA T674I-positive eosinophilic disorder, especially when compounded by the PTPN11 mutation. Resistance to standard treatments underscores the urgent need for novel therapies to manage this rare and aggressive disease.