Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2 – pro
The family of diseases generated by dysregulated fusion tyrosine kinase (TK) genes is recognized by the World Health Organization (WHO) category, “Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2.” In addition to myeloproliferative neoplasms (MPN), these patients can present with myelodysplastic syndrome/MPN, as well as de novo or secondary mixed-phenotype leukemias or lymphomas. Eosinophilia is a common, but not invariable, feature of these diseases.
Several studies have corroborated the high rates of complete hematologic remission (CHR) and complete molecular remission (CMR) with imatinib therapy of 100 to 400 mg daily in FIP1L1-PDGFRA-positive MPN-eo. Although the optimal induction dose is not defined, 100 mg daily is sufficient to elicit CMRs in a majority of patients. Maintenance doses as low as 100 to 200 mg weekly can sustain CMRs.36 The durability of these excellent outcomes has prompted investigators to assess the feasibility of stopping imatinib in those patients. Outcomes data are based on limited numbers of patients and reveal substantial variability in relapse-free survival. It is currently unknown what factors predict long-term CMR in these individuals, and therefore, discontinuation of imatinib should generally be undertaken in the context of clinical trials or registries.
Andreas Reiter and Jason Gotlib, Myeloid neoplasms with eosinophilia. Blood 2017 129:704-714;
Pardanani A, D’Souza A, Knudson RA, Hanson CA, Ketterling RP, Tefferi A. Long-term follow-up of FIP1L1-PDGFRA-mutated patients with eosinophilia: survival and clinical outcome. Leukemia. 2012;26(11):2439
Helbig G, Stella-Hołowiecka B, Majewski M, et al. A single weekly dose of imatinib is sufficient to induce and maintain remission of chronic eosinophilic leukaemia in FIP1L1-PDGFRA-expressing patients. Br J Haematol. 2008;141(2):200-204