Chronic eosinophilic leukemia‐not otherwise specified has a poor prognosis with unresponsiveness to conventional treatment and high risk of acute transformation

Abstract

Chronic eosinophilic leukemia-not otherwise specified (CEL-NOS) is a rare disorder with hypereosinophilia and an increased number of blood or marrow blast (<20%) or an evidence of eosinophil clonality. We evaluated the clinical outcome of 10 patients with CEL-NOS. Seven males and three females at a median age of 62 years (range, 23-73) were included. The median leukocyte count at diagnosis was 33.4 3 10 9 /l (range, 9.3-175.0) with a median eosinophil count of 15.6 3 10 9 /l (range, 1.5-136.0). Median hemoglobin and platelets were 11.0 g/dl (range, 8.3-13.3) and 158 3 10 9 /l (range, 31.0-891.0), respectively. Clinical manifestations included splenomegaly (n 5 7), hepatomegaly (n 5 6), cardiac failure (n 5 2), and lung infiltrations (n 5 1). Median survival from diagnosis to death for entire cohort was 22.2 months (range, 2.2-186.2). Five of the 10 studied patients developed acute transformation (AT) after median of 20 months from diagnosis (range, 1.6-41.9). None of patients with AT is alive at the time of last follow-up. Median time from AT to death was 2 months (range, 1.0-6.1). Among five patients who did not develop AT, three died in active disease. Two patients are alive in complete remission; first underwent allogeneic stem-cell transplantation preceding by intensive induction chemotherapy; the second remains on imatinib with hydroxyurea. Except the latter patient, imatinib was ineffective in our study population. CEL-NOS is a rare and aggressive disease with high rate of AT and resistance to conventional treatment.Chronic eosinophilic leukemia-not otherwise specified (CEL-NOS) is a rare Philadelphia-negative myeloproliferative neoplasm, which is due to clonal proliferation of eosinophil precursors. Peripheral blood hypereosinophilia (>1.5 3 10 9 /l), an increased number of myeloblasts in blood or marrow (<20%) or an evidence of eosinophil clonality, are required for diagnosis. The cases of myeloid and lymphoid neoplasms with abnormalities of platelet-derived growth factor alpha (PDGFRA), platelet-derived growth factor beta (PDGFRB), and fibroblast growth factor receptor 1 (FGFR1) must be also excluded [1]. In a new WHO classification, CEL-NOS is listed in the category of myeloproliferative neoplasms [2], whereas it was incorporated under the heading of myeloproliferative forms of hypereosinophilic syndromes according to the classification of the Eosinophilic Working Group [3]. Regardless of the classification used, CEL-NOS remains an extremely rare entity with variable prognosis [1,4]. The efficacy of currently used therapeutic agents is limited, and the hematological responses are usually short-lived [5].Ten patients (seven males and three females) at a median age of 62 years (range, 23-73) were included in this study. The median leukocyte count at diagnosis was 33.4 3 10 9 /l with a median eosinophil count of 15.6 3 10 9 /l. Blood smear was dominated by mature eosinophils with a small number of younger forms, for example, eosinophilic myelocytes and promyelocytes. Single eosinophils had dysplastic fe...

Targeted next-generation sequencing identifies a subset of idiopathic hypereosinophilic syndrome with features similar to chronic eosinophilic leukemia, not otherwise specified

“…In our study, chronic eosinophilic leukemia, not otherwise specified patients had a median disease-specific survival of 14.4 months, and three cases progressed to acute myeloid leukemia or accelerated phase. Our findings are similar to those reported by Helbig and colleagues 27 and suggest that chronic eosinophilic leukemia, not otherwise specified is a clinically aggressive disease, often resistant to therapy, with a relatively high rate of acute myeloid leukemia transformation and a short survival. In contrast, idiopathic hypereosinophilic syndrome patients with no identifiable mutations presented with hypereosinophilia at a much younger age than chronic eosinophilic leukemia, not otherwise specified, and had more frequent symptoms associated with eosinophil activation, such as dermatological, pulmonary, gastrointestinal, and rheumatologic manifestations, as has been reported by others.…”

A case of eosinophilic disorder that evolved in acute lymphoblastyc leukemia

“…The case was classified as acute common lymphoblastic leukemia (LLA), developed from a chronic eosinophilic leukemia not otherwise specified (CEL-NOS). Although acute transformation has already been described as a possible clinical outcome for CEL-NOS, LLA transformation has rarely been reported [1]. Primary eosinophilias encompass a group of hematologic disorders with potential for end-organ damage and acute transformation.…”

Chronic Eosinophilic Leukemia: A Mini-Review

“…In cases of CEL where the RT-PCR for FIP1L1-PDGFRA is negative or unknown, the prognosis is poor, being unresponsive or short lived to imatinib [25], conventional therapy [26] and has a high rate of acute transformation [26]. However, it has been reported that approximately 40% of patients who response to imatinib are negative for the FIP1L1-PDGFRA fusion protein, although doses as high as 600mg/day may not be effective [27].…”

“…The complete response rate has been reported as 24% compared with 98% of cases which were FIP1L1-PDGFRA positive [16]. However, hematological responses are often partial and short lived [26].…”

“…Nevertheless the prognosis of CEL-NOS is poor in a cohort of 10 patients; the median survival was 22.2 months, with acute transformation occurring in 5 of the 10 patients [26].…”