- Mohamad Jawhar1,
- Juliana Schwaab1,
- Manja Meggendorfer2,
- Nicole Naumann1,
- Hans-Peter Horny3,
- Karl Sotlar4,
- Torsten Haferlach2,
- Karla Schmitt5,
- Alice Fabarius1,
- Peter Valent6,
- Wolf-Karsten Hofmann1,
- Nicholas C.P. Cross7,
- Georgia Metzgeroth1 and
- Andreas Reiter1,*
- 1 Medical Faculty Mannheim, Heidelberg University, Germany;
- 2 Munich Leukemia Laboratory, Munich, Germany;
- 3 Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany;
- 4 University Institute of Pathology, University Hospital Salzburg, Paracelsus Medical University;
- 5 Department of Hematology and Oncology, University Hospital Aachen, Germany;
- 6 Dept of Inter. Med. I, Div. of Hematology and Ludwig Boltzmann Cluster Oncology, Vienna, Austria;
- 7 Wessex Regional Genetics Laboratory, Salisbury, U.K.
- ↵* Corresponding author; email:
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.
- Received January 6, 2017.
- Accepted February 28, 2017.
- Copyright © 2017, Ferrata Storti Foundation