Mast cell leukemia: clinical and molecular features and survival outcomes of patients in the ECNM Registry

Authors	KENNEDY Vanessa E PERKINS Cecelia REITER Andreas JAWHAR Mohamad LUEBKE Johannes KLUIN-NELEMANS Hanneke C SHOMALI William LANGFORD Cheryl ABUEL Justin HERMINE Olivier NIEDOSZYTKO Marek GORSKA Aleksandra MITAL Andrzej BONADONNA Patrizia ZANOTTI Roberta TANASI Ilaria MATTSSON Mattias HAGGLUND Hans TRIGGIANI Massimo YAVUZ Akif Selim PANSE Jens CHRISTEN Deborah HEIZMANN Marc SHOUMARIYEH Khalid MUELLER Sabine ELENA Chiara MALCOVATI Luca FIORELLI Nicolas WORTMANN Friederike VUCINIC Vladan BROCKOW Knut FOKOLOROS Christos PAPAGEORGIOU Sotirios G BREYNAERT Christine BULLENS Dominique DOUBEK Michael ILERHAUS Anja ANGELOVA-FISCHER Irena SOLOMIANYI Oleksii VARKONYI Judit SABATO Vito RUEFER Axel SCHUG Tanja Daniela HERMANS Maud A W FORTINA Anna Belloni CAROPPO Francesca BUMBEA Horia GULEN Theo HARTMANN Karin ELBERINK Hanneke Oude SCHWAAB Juliana AROCK Michel VALENT Peter SPERR Wolfgang R GOTLIB Jason
Year of publication	2023
Type	Article in Periodical
Magazine / Source	Blood advances
MU Faculty or unit	Faculty of Medicine
Citation
Web	https://ashpublications.org/bloodadvances/article/7/9/1713/486570/Mast-cell-leukemia-clinical-and-molecular-features
Doi	http://dx.doi.org/10.1182/bloodadvances.2022008292
Keywords	Mast cell leukemia
Description	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.