Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions: reevaluation of the defining characteristics in a registry-based cohort

Abstract

In a registry-based analysis of 135 patients with "myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions" (MLN-TK; FIP1L1::PDGFRA, n = 78; PDGFRB, diverse fusions, n = 26; FGFR1, diverse, n = 9; JAK2, diverse, n = 11; ETV6::ABL1, n = 11), we sought to evaluate the disease-defining characteristics. In 81/135 (60%) evaluable patients, hypereosinophilia (>1.5 × 10⁹/l) was observed in 40/44 (91%) FIP1L1::PDGFRA and 7/7 (100%) ETV6::ABL1 positive patients but only in 13/30 (43%) patients with PDGFRB, FGFR1, and JAK2 fusion genes while 9/30 (30%) patients had no eosinophilia. Monocytosis >1 × 10⁹/l was identified in 27/81 (33%) patients, most frequently in association with hypereosinophilia (23/27, 85%). Overall, a blast phase (BP) was diagnosed in 38/135 (28%) patients (myeloid, 61%; lymphoid, 39%), which was at extramedullary sites in 18 (47%) patients. The comparison between patients with PDGFRA/PDGFRB vs. FGFR1, JAK2, and ETV6::ABL1 fusion genes revealed a similar occurrence of primary BP (17/104, 16% vs. 8/31 26%, p = 0.32), a lower frequency (5/87, 6% vs. 8/23, 35%, p = 0.003) of and a later progression (median 87 vs. 19 months, p = 0.053) into secondary BP, and a better overall survival from diagnosis of BP (17.1 vs. 1.7 years, p < 0.0008). We conclude that hypereosinophilia with or without monocytosis and various phenotypes of BP occur at variable frequencies in MLN-TK.

Fig. 1. Overall surviall of all patients.

A Overall survival (OS) from time of diagnosis of 135 patients with various tyrosine kinase fusion genes (PDGFRA, n = 78; PDGFRB, n = 26; FGFR1, n = 9; JAK2, n = 11; ETV6::ABL1, n = 11) independent of disease phase. B OS of patients with PDGFRA/PDGFRB (FIP1L1::PDGFRA, n = 65; PDGFRB, n = 22) and FGFR1, JAK2 and ETV6::ABL1 (FGFR1, n = 3; JAK2, n = 11; ETV6::ABL1, n = 9) fusion genes in chronic phase (including 13 patients with progression into secondary blast phase), median follow-up 9.7 years (0–34.0) and 2.2 years (0.1–6.3), respectively (p < 0.0001). C OS of patients with PDGFRA/PDGFRB (FIP1L1::PDGFRA, n = 17; PDGFRB, n = 5) and FGFR1, JAK2 and ETV6::ABL1 (FGFR1, n = 7; JAK2, n = 3; ETV6::ABL1, n = 6) fusion genes from diagnosis of blast phase (primary BP, n = 25, secondary BP, n = 13), median OS 17.1 years (range 0.2–22) vs. 1.7 years (range 0.1–5.5; p = 0.0008). D OS of patients after allogeneic stem cell transplantation in prior chronic (n = 12) or blast phase (n = 13) independent of underlying TK fusion gene.