Complete Response of Myeloid/Lymphoid Neoplasms with PDGFRA Rearrangement Presenting as Leukemia/Myeloid Sarcoma to Imatinib Monotherapy
Myeloid/lymphoid neoplasms with eosinophilia and platelet-derived growth factor receptor alpha (PDGFRA) rearrangement represent a distinct category of hematopoietic disorders, as classified by the World Health Organization (WHO) since 2008. These neoplasms are characterized by the presence of the FIP1L1-PDGFRA (F/P) fusion gene, which encodes a constitutively active tyrosine kinase. This fusion gene is responsible for approximately 23% of all eosinophilias, with reported prevalence ranging from 3% to 56%. The F/P fusion protein is highly sensitive to tyrosine kinase inhibitors (TKIs), making them the first-line therapy for this condition according to WHO guidelines.
While most cases of F/P-positive eosinophilia present in a chronic phase with minimal or no increase in bone marrow (BM) blasts, rare cases have been reported to present as more aggressive forms, such as acute myeloid leukemia (AML) or myeloid sarcoma. In these aggressive presentations, the optimal treatment strategy—whether imatinib monotherapy or combination therapy with chemotherapy, radiotherapy, or hematopoietic stem cell transplantation—remains unclear. This article describes two cases of myeloid/lymphoid neoplasms with PDGFRA rearrangement presenting as leukemia or myeloid sarcoma, both of which achieved complete response to imatinib monotherapy.
Case 1: Myeloid Sarcoma with F/P Rearrangement
The first patient was a 33-year-old man with no prior medical history who presented with a palpable chest mass that had gradually increased in size over one month. Positron emission tomography-computed tomography (PET-CT) revealed hypermetabolic lesions throughout the body, with the largest lesion located in the left chest wall (6.9 cm × 3.3 cm), invading adjacent tissues. A biopsy of the mass confirmed a diagnosis of sarcoma with an immunohistochemical phenotype positive for myeloperoxidase, CD34, and CD117. Blood tests revealed eosinophilia (3.86 × 10^9/L, 49.2% of white blood cell count [WBC]) with normal hemoglobin and platelet levels. Bone marrow aspirates showed an infiltration of 22% eosinophils, and reverse transcription-polymerase chain reaction (RT-PCR) detected the presence of the F/P fusion gene at a level of 0.28%. A definitive diagnosis of myeloid neoplasm with eosinophilia and F/P rearrangement was made.
The patient initially received two cycles of chemotherapy, which reduced the F/P transcript level to 0.037%. However, the chest tumor did not shrink, and PET-CT continued to show multiple fluorodeoxyglucose hypermetabolic lesions. Imatinib monotherapy was initiated at a standard dose of 400 mg/day on March 11, 2016. Remarkably, within nine days, the chest mass had significantly reduced in size. A repeat bone marrow test one month later showed no detectable F/P fusion transcripts, indicating complete molecular remission (CMR). The patient was subsequently maintained on a lower dose of imatinib (200 mg/week) and has remained in sustained CMR.
Case 2: Acute Myeloid Leukemia with F/P Rearrangement
The second patient was a 25-year-old man admitted with a one-week history of intermittent fever. Blood tests revealed eosinophilia (2.89 × 10^9/L, 20.6% of WBC count), along with reduced hemoglobin (81 g/L) and platelet counts (48 × 10^9/L). Bone marrow aspirates showed increased myeloblasts (27%), monoblasts (31%), and eosinophils (26%), meeting the criteria for AML-M4 according to the French-American-British classification. Flow cytometry confirmed the presence of blasts with a phenotype positive for CD34, CD123, and dimly positive for CD33 and CD13. Initial suspicion of AML-M4 with bone marrow eosinophilia (AML-M4Eo) was raised; however, RT-PCR did not detect the core-binding transcription factor beta-myosin-11 (CBFβ-MYH11) fusion gene. Instead, the F/P fusion gene was detected at a level of 4.6%, leading to a diagnosis of myeloid neoplasm with eosinophilia and F/P rearrangement.
Based on the successful outcome in the first patient, imatinib monotherapy was initiated at a standard dose of 400 mg/day on January 13, 2017, without prior chemotherapy. Within one month, the patient’s eosinophil count normalized, and bone marrow tests indicated complete morphologic remission with minimal residual disease negativity. The F/P transcript level decreased to 1.2%. Imatinib therapy was continued, and four months later, F/P gene testing was negative, confirming CMR. The patient remains on imatinib monotherapy at a reduced dose of 200 mg/day and has maintained CMR.
Discussion
These two cases highlight the efficacy of imatinib monotherapy in treating aggressive presentations of myeloid/lymphoid neoplasms with PDGFRA rearrangement, such as AML and myeloid sarcoma. The rapid and sustained responses observed in both patients underscore the importance of early identification of the F/P fusion gene, even in cases presenting with high blast counts or extramedullary involvement.
The F/P fusion gene encodes a constitutively active tyrosine kinase that drives the proliferation of eosinophils and other myeloid cells. Imatinib, a first-generation TKI, specifically targets this fusion protein, leading to inhibition of downstream signaling pathways and subsequent cell death. The rapid reduction in tumor size and normalization of blood counts observed in these cases demonstrate the potent therapeutic effect of imatinib in F/P-positive neoplasms.
While most reported cases of F/P-positive eosinophilia present in a chronic phase, the aggressive presentations described here are rare but clinically significant. The successful outcomes in these cases suggest that imatinib monotherapy may be sufficient to induce remission, even in advanced disease states. However, due to the rarity of these presentations and the heterogeneity of treatment approaches in the literature, further studies are needed to determine whether imatinib monotherapy is superior to combination therapies in such cases.
Conclusion
The cases presented here demonstrate that myeloid/lymphoid neoplasms with PDGFRA rearrangement can present as aggressive diseases such as AML or myeloid sarcoma. Both patients achieved complete molecular remission with imatinib monotherapy, highlighting the efficacy of this treatment approach. Early screening for the F/P fusion gene in patients with eosinophilia and leukemic or sarcomatous presentations is crucial for appropriate treatment selection. While long-term follow-up is necessary to assess the durability of remission, these cases provide valuable insights into the management of this rare but treatable condition.
doi.org/10.1097/CM9.0000000000000437
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