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Apostolou, C.1; Klonizakis, P.2; Kafantari, A.3; Theodoridou, S.4; Lalayanni, C.5; Panayiotidis, P.6; Vlachaki, E.2

doi: 10.1097/01.HS9.0000567724.63782.40
Publication Only: Sickle cell disease

1Thalassemia Unit,Second Department of Internal Medicine,Aristotle Unversity of Thessaloniki

2Thalassemia Unit,Second Department of Internal Medicine, Aristotle University of Thessaloniki

3Second Department of Internal Medicine,Aristotle University of Thessaloniki

4Thalassemia Prevention Unit, Hippokration General Hospital

5Hematology Department And BMT Unit, General Hospital “George Papanikoloaou”, THESSALONIKI

6Hematology section,Fist Department of Propedeutic Iinternal Medicine National and Kapodistrian University of Athens, Laikon University Haspital, Athens, Greece

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Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm, for which current WHO diagnostic criteria include leukocytosis of ≥25 × 109 /L of which ≥80% are neutrophils, with <10% circulating neutrophil precursors with blasts rarely observed. In addition, there is no dysplasia, nor clinical or molecular criteria for other myeloproliferative neoplasms. The true incidence of CNL is unknown, but only 200 cases have been reported.Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by abnormal hemoglobin production(HbS) which leads to hemolytic anemia and intermittent occlusion of small blood vessels.

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Case report of a 55 years old patient with double heterozygous sickle cell/β + thal disease, first diagnosed at age of 45, who now suffers from CNL, ten years post treatment for acute myeloid leukemia (AML).

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A 55 years old male patient was referred to our clinic in 2012 with the diagnosis of double heterozygous sickle cell/β + thal disease. He was initated on red cell exchange transfusions due to sickle cell hepatopathy. Ten years earlier he had received intensive chemotherapy for AML with myelomonocytic differentiation, CBFB/MYH11(+). He attained a complete morphological and cytogenetic remission after 1st induction. He remained in CR until 2015 when he presented with worsening anemia that could not be attributed to his hemoglobinopathy(Hb = 8 g/dl). A complete work up including bone marrow aspiration, biopsy, molecular testing for CBFB/MYH11 and cytogenetics were normal. In 2018, he presented with a severe sickle cell crisis with multi-organ failure during an infection and he started hydroxycarvamide at a dose of 500 mg. During the next months a progressive increase of WBC counts with elevated neutrophils was noticed and was attributed to dental abscess. Leukocytosis insisted despite appropriate treatment so he was admitted to the clinic. A complete work up, including imaging, virology, blood and urine cultures revealed no sign of infection or malignancy. Despite hydroxycarbamide treatment leukocytosis persisted (WBC: 90 × 109/L, ≥95% neutrophils, Hb: 8 g/dl, PLT:180000), with no circulating neutrophil precursors or myeloblasts and no evidence of dysplasia.Bone marrow biopsy was repeated. This time an hypercellular marrow with increased neutrophils, normal maturation and blasts <5% raised the question of a myeloproliferative neoplasm. The patient did not fulfill WHO criteria for Ph + CML, PMF, PV or ET. Analysis of a myeloid panel by Next generation sequencing(NGS) revealed the presence of the following mutations: CSF3R T618I, VAF:38% and SETBP1 G870Ser, VAF:54%.

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A diagnosis of Chronic Neutrophilic Leukenmia was made according to the WHO classification. Hydroxycarbamide at a dose of 2gr was started,since patient was not eligible for bone barrow transplantation. Five months later,patient remains in good condition and has no evidence of disease progression.Further investigation will involve the detection of driver mutations in the bone marrow sample from the primary AML diagnosis using NGS.

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Although the clinical course of CNL is variable, the overall prognosis is generally reserved with a substantial portion of patients eventually progressing to blast crisis,The median overall survival is 24 months. Effective management has been hampered by the rarity of the disease, the lack of prospective trials, and the limited therapeutic options.The most common therapeutic approaches are Hydroxyurea, Interferon and Ruxolitinib. Our patient shows an initial response in Hydroxyurea therapy.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.