Diagnosis and Treatment of Clonal Myeloproliferative Neoplasms with Eosinophilia

Abstract

Aim. Based on our own materials to characterize the clinical manifestations of hypereosinophilic states distinguishing between reactive eosinophilia (RE), clonal myeloproliferative neoplasms with eosinophilia (MPN-eo), and myeloproliferative variant of hypereosinophilic syndrome (MP-HES); to evaluate treatment results. Materials & Methods. The trial included 188 patients with primary HES (132 men and 56 women, aged 19-72 years) having been followed-up at the National Research Center for Hematology since 2001. The main entry criteria were blood eosinophilia > 1.5 ^x 10⁹/L and clinical symptoms resulting sometimes from hypereosinophilia. All patients received complete physical examination, immunomorphological, standard cytogenetic, and molecular genetic testing. Treatment was provided to 73 patients (63 men and 10 women) including those with MPN-eo PDGFRA+ (п = 39), PDGFRB+ (п = 2), FGFR1+ (п = 1), chronic eosinophilic leukemia not otherwise specified (п = 8), systemic mastocytosis (п = 1), and MP-HES (п = 22). Complete hematological response (CHR) was the criterion for treatment efficacy. In the MPN-eo PDGFRA+ and PDGFRB+ groups molecular response (MR) rate was also estimated in cases of imatinib treatment. MR was considered as no expression of the FIP1L1-PDGFRA and ETV6-PDGFRB transcripts in RT-PCR. Results. The trial yielded the cause of eosinophilia in 117 (62.2 %) out of 188 patients. RE was diagnosed in 60 (32 %) out of 117 patients, various types of clonal MPNs were reported in 57 (30 %) patients. In 71 (38 %) out of 188 patients HES was still present at the first trial stages. Later within this group MP-HES was identified in 22 (30.9 %) out of 71 patients. Among imatinib recipients CHR was achieved in 37 (90 %) out of 41 patients within 1-3 months: in 36 patients with MPN-eo FIP1L1-PDGFRA+ and in 1 patient with MPN-eo ETV6-PDGFRB+. MR was achieved in 88 % of cases. In the absence of molecular markers characteristic of MPN-eo CHR was achieved in 26 % of cases. Among the recipients of treatments other than imatinib nobody achieved CHR. Conclusion. The diagnosis approach in patients with HES should be complex and individualized. Development and enhancement of molecular genetic diagnostic techniques are regarded as ones of the highest priority areas in modern hematology. The use of imatinib mesylate in MPN-eo therapy commonly results in long-term hematological and molecular remissions. On achieving CHR to imatinib treatment of patients without molecular markers characteristic of MPN-eo early use of this drug (or other tyrosine kinase inhibitors) can be recommended in acute forms of HES.