Mast cell leukemia (MCL) is a rare subtype of systemic mastocytosis defined by ≥20% mast cells (MC) on a bone marrow aspirate. We evaluated 92 patients with MCL from the European Competence Network on Mastocytosis registry. Thirty-one (34%) patients had a diagnosis of MCL with an associated hematologic neoplasm (MCL-AHN). Chronic MCL (lack of C-findings) comprised 14% of patients, and only 4.5% had "leukemic MCL" (≥10% circulating MCs). KIT D816V was found in 62/85 (73%) evaluable patients; 9 (11%) individuals exhibited alternative KIT mutations, and no KIT variants were detected in 14 (17%) subjects. Ten evaluable patients (17%) had an abnormal karyotype and the poor-risk SRSF2, ASXL1, and RUNX1 (S/A/R) mutations were identified in 16/36 (44%) patients who underwent next-generation sequencing. Midostaurin was the most common therapy administered to 65% of patients and 45% as first-line therapy. The median overall survival (OS) was 1.6 years. In multivariate analysis (S/A/R mutations excluded owing to low event rates), a diagnosis of MCL-AHN (hazard ratio [HR], 4.7; 95% confidence interval [CI], 1.7-13.0; P = .001) and abnormal karyotype (HR, 5.6; 95% CI, 1.4-13.3; P = .02) were associated with inferior OS; KIT D816V positivity (HR, 0.33; 95% CI, 0.11-0.98; P = .04) and midostaurin treatment (HR, 0.32; 95% CI, 0.08-0.72; P = .008) were associated with superior OS. These data provide the most comprehensive snapshot of the clinicopathologic, molecular, and treatment landscape of MCL to date, and should help further inform subtyping and prognostication of MCL.

2nd Propaedeutic Department of Internal Medicine and Research Institute Hematology Unit University of Athens Attikon University Hospital Athens Greece

Brno University Hospital and Faculty of Medicine Brno Czechia

Department of Allergology Medical University of Gdansk Gdańsk Poland

Department of Dermatology and Allergy Biederstein School of Medicine Technical University of Munich Munich Germany

Department of Dermatology Medical Center University of Frieburg Faculty of Medicine University of Frieburg Frieburg Germany

Department of Hematology and Oncology University Hospital Mannheim Heidelberg University Mannheim Germany

Department of Hematology Carol Davila University of Medicine Emergency University Hospital Bucharest Romania

Department of Hematology Medical University of Gdansk Gdańsk Poland

Department of Hematology Semmelweis University Budapest Hungary

Department of Hematology Uppsala University Hospital and Department of Immunology Genetics and Pathology Uppsala University Uppsala Sweden

Department of Immunology Allergy and Rheumatology Universiteit Antwerpen Campus Drie Eiken Antwerp Belgium

Department of Internal Medicine Section Allergy and Clinical Immunology Erasmus Medical Center Rotterdam The Netherlands

Department of Medicine 1 Medical Center University of Freiburg Faculty of Medicine University of Freiburg and German Cancer Consortium Partner Site Freiburg Freiburg Germany

Department of Medicine Section of Hematology Verona University Hospital Verona Italy

Department of Oncology Haematology Haemostaseology and Stem Cell Transplantation University Hospital RWTH Aachen and Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf Aachen Germany

Department of Respiratory Medicine and Allergy Karolinska University Hospital Huddinge and Department of Medicine Solna Karolinska Institutet Stockholm Sweden

Division of Allergy and Clinical Immunology University of Salerno Salerno Italy

Division of Allergy Departments of Dermatology and Biomedicine University Hospital Basel and University of Basel Basel Switzerland

Division of Hematology and Hemostaseology Department of Internal Medicine 1 Medical University of Vienna Vienna Austria

Division of Hematology Istanbul Medical School University of Istanbul Istanbul Turkey

Division of Oncology Haematology and Transfusion Medicine Kantonsspital Aarau AG University Clinic of Medicine Aarau Switzerland

Hematology Unit Fondazione IRCCS Policlinico San Matteo Pavia Italy

Imagine Institute Université de Paris Sorbonne INSERM U1163 Centre national de référence des mastocytoses Hôpital Necker Assistance publique hôpitaux de Paris Paris France

Kepler University Hospital Linz Austria

Klinik für Hämatologie und Onkologie Universitätsklinikum Schleswig Holstein Lübeck Germany

KU Leuven Department of Microbiology Immunology and Transplantation Allergy and Clinical Immunology Research Group and MASTeL University Hospitals Leuven Leuven Belgium

Laboratory of Hematology Pitié Salpêtrière Hospital Paris France

Ludwig Boltzmann Institute for Hematology and Oncology Medical University of Vienna Vienna Austria

Luzerner Kantonsspital Lucerne Switzerland

Mastocytosis Clinic Allergy Unit 2nd Department of Dermatology and Venereology University of Athens Attikon General University Hospital Athens Greece

Pediatric Dermatology Internal Medicine Azienda Ospedaliera Università di Padov Padua Italy

Stanford Cancer Institute Stanford University School of Medicine Stanford CA

Uniklinik Köln Klinik für Dermatologie und Venerologie Cologne Germany

Univ Klinik für Dermatologie Medical University of Graz Graz Austria

Universitätsklinikum Leipzig AöR Leipzig Germany

University Medical Center Groningen University of Groningen Groningen The Netherlands

University of California San Francisco CA

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