Complete Responses of Myeloid/Lymphoid Neoplasms with Rearrangement of Pdgfra Presenting As AML/ALL/Myeloid Sarcoma to Imatinib Monotherapy

Background Patients with eosinophilia and FIP1L1-PDGFRA fusion protein accounted for approximately 23% (range, 3%-56%) of hyper-eosinophilias. In the 2008 and 2016 WHO classification of myeloid neoplasms, myeloid/lymphoid neoplasms with rearrangement of PDGFRA have been categorized as a distinct type of hematopoietic disorders. Reported cases mostly exhibit normal or mildly elevated bone marrow blasts at diagnosis and imatinib monotherapy is sufficient to induce rapid and complete hematopoietic responses. Patients with rearrangement of PDGFRA but presenting as AML/ALL or myeloid sarcomas are rare and the efficacy of imatinib monotherapy in these patients remains undefined.

Methods Two male patients were diagnosed as myeloid neoplasms with rearrangement of PDGFRA in our hospital in 2016. Patient One (aged 31) was presenting as myeloid sarcoma with a 6.9×3.3cm mass on his chest wall and was treated with chemotherapy plus imatinib. Patient Two (aged 25) was presenting as AML with a bone marrow blasts of 27% and was treated with imatinib monotherapy. A literature review searching for patients with PDGFRA rearrangement but presented as AML/ALL/myeloid sarcoma was performed and efficacy of imatinib monotherapy was explored.

Results Both of the cases from our hospital survived. Patient One received two cycles of standard chemotherapy (MA and IA) but failed to reduce the tumor size. Imatinib (400mg/d) was initiated immediately. His tumor shrunk dramatically in one week and he achieved complete molecular remission (CMR) in 4 weeks. Patient Two receiving imatinib monotherapy achieved complete hematopoietic remission (CHR) in 1 month and CMR in 3 months after initiation of imatinib (400mg/d). Both patients remain CHR and CMR till now (8 months and 18 months, respectively). We combined our data with 24 cases found in literature that presented as AML/ALL/myeloid sarcoma at diagnosis. All 26 patients were male, and the median age was 40 years (range, 21 to 46). We further compared outcomes of patients treated with imatinib monotherapy or with chemotherapy/HSCT plus imatinib. Most cases in the latter group were given imatinib after chemotherapy induction due to persistent eosinophilia, unsatisfied regress of tumor mass, continued positivity of PDGFRA fusion gene, or disease relapse. The 3-year probabilities of overall survival (OS) were 87.5% for the monotherapy group and 80% for the plus chemotherapy/HSCT group, which were of no statistical significance (p=0.919). In each group there was one patient died from imatinib resistance caused by a mutation in the fusion gene.

Conclusions We reported two rare cases of myeloid neoplasms with rearrangement of PDGFRA but presenting as AML/myeloid sarcoma at diagnosis and showed their excellent responses to imatinib. By pooling data in literature we suggest imatinib monotherapy was comparable to combination of chemotherapy/HSCT and imatinib in overall survival rate. To our knowledge, this is the first study to specifically explore outcomes of various treatments for this disease. The efficacy of imatinib monotherapy emphasized importance of FIP1L1-PDGFRA detection at diagnosis of hematopoietic malignancies with eosinophilias.