The clinical and molecular diversity of mast cell leukemia with or without associated hematologic neoplasm

• Verfasst von: Jawhar, Mohamad [VerfasserIn]
• Verfasst von: Schwaab, Juliana [VerfasserIn]
• Verfasst von: Naumann, Nicole [VerfasserIn]
• Verfasst von: Fabarius, Alice [VerfasserIn]
• Verfasst von: Hofmann, Wolf-Karsten [VerfasserIn]
• Verfasst von: Metzgeroth, Georgia [VerfasserIn]
• Verfasst von: Reiter, Andreas [VerfasserIn]
• Titel: The clinical and molecular diversity of mast cell leukemia with or without associated hematologic neoplasm
• Verf.angabe: Mohamad Jawhar, Juliana Schwaab, Manja Meggendorfer, Nicole Naumann, Hans-Peter Horny, Karl Sotlar, Torsten Haferlach, Karla Schmitt, Alice Fabarius, Peter Valent, Wolf-Karsten Hofmann, Nicholas C.P. Cross, Georgia Metzgeroth, Andreas Reiter
• E-Jahr: 2017
• Jahr: March 2, 2017
• Umfang: 9 S.
• Fussnoten: Pre-published: March 2, 2017 ; Gesehen am 16.08.2018
• Titel Quelle: Enthalten in: Haematologica
• Ort Quelle: Pavia : Ferrata Storti Foundation, 2014
• Jahr Quelle: 2017
• Band/Heft Quelle: 102(2017), 6, Seite 1035-1043
• ISSN Quelle: 1592-8721
• DOI: doi:10.3324/haematol.2017.163964
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1580126383

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 novo mast 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 in KIT (D816V, n=19; D816H/Y, n=5; F522C, n=1) were detected in 25 of 28 (89%) patients and prognostically relevant additional mutations in SRSF2, ASXL1 or RUNX1 (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/Rpos adversely 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/Rpos remained 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.