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 ≥20% 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 16/28 (57%) patients and secondary mast cell leukemia evolving from other advanced systemic mastocytosis subtypes in 12/28 (43%) patients, of which 7 patients progressed while on cytoreductive treatment. Median bone marrow mast cell infiltration was 65% and median serum tryptase was 565 microg/L. C-findings were identified in 26/28 (93%) patients. Mutations in KIT (D816V, n=19; D816H/Y, n=5; F522C, n=1) were detected in 25/28 (89%) patients and prognostically relevant additional mutations in SRSF2, ASXL1 or RUNX1 (S/A/Rpos) in 13/25 (52%) patients. Overall response rate in 18 treatment-naive patients was 5/12 (42%) on midostaurin and 1/6 (17%) on cladribine, and after switch 1/4 (25%) on midostaurin and 0/3 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.

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ORCID for Nicholas C.p. Cross: orcid.org/0000-0001-5481-2555

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