The University of Southampton
University of Southampton Institutional Repository

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

The clinical and molecular diversity of mast cell leukemia with or without associated hematologic neoplasm
The clinical and molecular diversity of mast cell leukemia with or without associated hematologic neoplasm
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.
0390-6078
1035-1043
Jawhar, Mohamad
a608a215-173b-47bd-89eb-a8de2fe595aa
Schwaab, Juliana
d63ed545-a6fc-4815-ab86-f901e55c2a2f
Meggendorfer, Manja
3e6a7136-7586-4220-8c3c-512e0c872f2d
Naumann, Nicole
43566136-d964-415e-be36-45aeb4f88965
Horny, Hans-peter
95077a3b-b869-49ba-a227-f88b2c0bad80
Sotlar, Karl
e3e96797-3fab-4c37-8728-7c77bb3ba389
Haferlach, Torsten
fff2c7bf-3212-45e3-a731-19ea532c1137
Schmitt, Karla
89008666-a71b-4738-8163-6b705ae2ddc8
Fabarius, Alice
5c31b1e0-c6da-49b8-843a-5b0ca736e5a2
Valent, Peter
1f551798-afce-4de4-abed-9efd78bc2e8a
Hofmann, Wolf-karsten
ab66838b-bf8c-4352-a0f0-3c8aafed2570
Cross, Nicholas C.p.
f87650da-b908-4a34-b31b-d62c5f186fe4
Metzgeroth, Georgia
611ec46d-9a11-4e24-ae0f-5ac19dfd0237
Reiter, Andreas
ffa23e84-4a13-4cb5-aaf0-3fafe25dbede
Jawhar, Mohamad
a608a215-173b-47bd-89eb-a8de2fe595aa
Schwaab, Juliana
d63ed545-a6fc-4815-ab86-f901e55c2a2f
Meggendorfer, Manja
3e6a7136-7586-4220-8c3c-512e0c872f2d
Naumann, Nicole
43566136-d964-415e-be36-45aeb4f88965
Horny, Hans-peter
95077a3b-b869-49ba-a227-f88b2c0bad80
Sotlar, Karl
e3e96797-3fab-4c37-8728-7c77bb3ba389
Haferlach, Torsten
fff2c7bf-3212-45e3-a731-19ea532c1137
Schmitt, Karla
89008666-a71b-4738-8163-6b705ae2ddc8
Fabarius, Alice
5c31b1e0-c6da-49b8-843a-5b0ca736e5a2
Valent, Peter
1f551798-afce-4de4-abed-9efd78bc2e8a
Hofmann, Wolf-karsten
ab66838b-bf8c-4352-a0f0-3c8aafed2570
Cross, Nicholas C.p.
f87650da-b908-4a34-b31b-d62c5f186fe4
Metzgeroth, Georgia
611ec46d-9a11-4e24-ae0f-5ac19dfd0237
Reiter, Andreas
ffa23e84-4a13-4cb5-aaf0-3fafe25dbede

Jawhar, Mohamad, Schwaab, Juliana, Meggendorfer, Manja, Naumann, Nicole, Horny, Hans-peter, Sotlar, Karl, Haferlach, Torsten, Schmitt, Karla, Fabarius, Alice, Valent, Peter, Hofmann, Wolf-karsten, Cross, Nicholas C.p., Metzgeroth, Georgia and Reiter, Andreas (2017) The clinical and molecular diversity of mast cell leukemia with or without associated hematologic neoplasm. Haematologica, 102 (6), 1035-1043. (doi:10.3324/haematol.2017.163964).

Record type: Article

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.

Text
haematol 2017 163964 full - Accepted Manuscript
Restricted to Repository staff only
Request a copy

More information

Accepted/In Press date: 28 February 2017
e-pub ahead of print date: 2 March 2017
Published date: June 2017
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 406183
URI: http://eprints.soton.ac.uk/id/eprint/406183
ISSN: 0390-6078
PURE UUID: 339d3e64-1d97-47b5-8db6-a4f36012e332
ORCID for Nicholas C.p. Cross: ORCID iD orcid.org/0000-0001-5481-2555

Catalogue record

Date deposited: 10 Mar 2017 10:41
Last modified: 16 Mar 2024 03:23

Export record

Altmetrics

Contributors

Author: Mohamad Jawhar
Author: Juliana Schwaab
Author: Manja Meggendorfer
Author: Nicole Naumann
Author: Hans-peter Horny
Author: Karl Sotlar
Author: Torsten Haferlach
Author: Karla Schmitt
Author: Alice Fabarius
Author: Peter Valent
Author: Wolf-karsten Hofmann
Author: Georgia Metzgeroth
Author: Andreas Reiter

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×