title: The clinical and molecular diversity of mast cell leukemia with or without associated hematologic neoplasm.
abstract: Mast cell leukemia is a rare variant of advanced systemic mastocytosis characterized by at least 20% of mast cells in a bone marrow smear. We evaluated clinical and molecular characteristics of 28 patients with (n=20, 71%) or without an associated hematologic neoplasm.De novomast cell leukemia was diagnosed in 16 of 28 (57%) patients and secondary mast cell leukemia evolving from other advanced systemic mastocytosis subtypes in 12 of 28 (43%) patients, of which 7 patients progressed while on cytoreductive treatment. Median bone marrow mast cell infiltration was 65% and median serum tryptase was 520 μg/L. C-findings were identified in 26 of 28 (93%) patients. Mutations inKIT(D816V, n=19; D816H/Y, n=5; F522C, n=1) were detected in 25 of 28 (89%) patients and prognostically relevant additional mutations inSRSF2,ASXL1orRUNX1(S/A/Rpos) in 13 of 25 (52%) patients. Overall response rate in 18 treatment-naïve patients was 5 of 12 (42%) on midostaurin and 1 of 6 (17%) on cladribine, and after switch 1 of 4 (25%) on midostaurin and 0 of 3 on cladribine, respectively. S/A/Rposadversely affected response to treatment and progression to secondary mast cell leukemia (n=6) or acute myeloid leukemia (n=3) while on treatment (P<0.05). The median overall survival from mast cell leukemia diagnosis was 17 months as compared to 44 months in a control group of 124 patients with advanced systemic mastocytosis but without mast cell leukemia (P=0.03). In multivariate analyses, S/A/Rposremained the only independent poor prognostic variable predicting overall survival (P=0.007). In conclusion, the molecular signature should be determined in all patients with mast cell leukemia because of its significant clinical and prognostic relevance.
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Germany.|Medical Faculty Mannheim, University of Heidelberg, Germany.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Jawhar
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Germany.|Medical Faculty Mannheim, University of Heidelberg, Germany.
authors.forename: Juliana
authors.initials: J
authors.lastname: Schwaab
authors.affiliation: Munich Leukemia Laboratory, Germany.
authors.forename: Manja
authors.initials: M
authors.lastname: Meggendorfer
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Germany.|Medical Faculty Mannheim, University of Heidelberg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Naumann
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Horny
authors.affiliation: University Institute of Pathology, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Karl
authors.initials: K
authors.lastname: Sotlar
authors.affiliation: Munich Leukemia Laboratory, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.affiliation: Department of Hematology and Oncology, University Hospital Aachen, Germany.
authors.forename: Karla
authors.initials: K
authors.lastname: Schmitt
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Germany.|Medical Faculty Mannheim, University of Heidelberg, Germany.
authors.forename: Alice
authors.initials: A
authors.lastname: Fabarius
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Germany.|Medical Faculty Mannheim, University of Heidelberg, Germany.
authors.forename: Wolf-Karsten
authors.initials: WK
authors.lastname: Hofmann
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury, UK.|Faculty of Medicine, University of Southampton, UK.
authors.forename: Nicholas C P
authors.initials: NCP
authors.lastname: Cross
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Germany.|Medical Faculty Mannheim, University of Heidelberg, Germany.
authors.forename: Georgia
authors.initials: G
authors.lastname: Metzgeroth
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Germany andreas.reiter@medma.uni-heidelberg.de.|Medical Faculty Mannheim, University of Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reiter
mesh_terms: D017338:Cladribine / Q000627:therapeutic use; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D018450:Disease Progression; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications*; D006801:Humans; D007946:Leukemia, Mast-Cell / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D034721:Mastocytosis, Systemic / Q000401:mortality; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics; D000068103:Serine-Arginine Splicing Factors / Q000235:genetics; D019311:Staurosporine / Q000031:analogs & derivatives / Q000627:therapeutic use; D015996:Survival Rate
chemical_list: C473949:ASXL1 protein, human; D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human; D012097:Repressor Proteins; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors; D017338:Cladribine; D019311:Staurosporine; C059539:midostaurin