Poor Applicability of Currently Available Prognostic Scoring Systems for Prediction of Outcome in KIT D816V-Negative Advanced Systemic Mastocytosis

Author:

Naumann Nicole1,Rudelius Martina2,Lübke Johannes1ORCID,Christen Deborah34,Bresser Jakob1,Sotlar Karl5,Metzgeroth Georgia1,Fabarius Alice1,Hofmann Wolf-Karsten1,Panse Jens34ORCID,Horny Hans-Peter2,Cross Nicholas C. P.67ORCID,Reiter Andreas1,Schwaab Juliana1ORCID

Affiliation:

1. Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany

2. Institute of Pathology, Ludwig-Maximilian-University, 80337 Munich, Germany

3. Department of Oncology, Haematology, Haemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, 52074 Aachen, Germany

4. Center for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf (ABCD), 52074 Aachen, Germany

5. Institute of Pathology, University Hospital Salzburg, Paracelsus Medical University, 5020 Salzburg, Austria

6. Wessex Genomics Laboratory Service, Salisbury SP2 8BJ, UK

7. Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK

Abstract

Within our nationwide registry, we identified a KIT D816V mutation (KIT D816Vpos.) in 280/299 (94%) patients with advanced systemic mastocytosis (AdvSM). Age, cytopenias and the presence of additional somatic mutations confer inferior overall survival (OS). However, little is known about the characteristics of KIT D816V-negative (D816Vneg.) AdvSM. In 19 D816Vneg. patients, a combination of clinical, morphological and genetic features revealed three subgroups: (a) KIT D816H- or Y-positive SM (KIT D816H/Ypos., n = 7), predominantly presenting as mast cell leukemia (MCL; 6/7 patients), (b) MCL with negative KIT sequencing (KITneg. MCL, n = 7) and (c) KITneg. SM with associated hematologic neoplasm (KITneg. SM-AHN, n = 5). Although >70% of patients in the two MCL cohorts (KIT D816H/Ypos. and KITneg.) were classified as low/intermediate risk according to prognostic scoring systems (PSS), treatment response was poor and median OS was shorter than in a KIT D816Vpos. MCL control cohort (n = 29; 1.7 vs. 0.9 vs. 2.6 years; p < 0.04). The KITneg. SM-AHN phenotype was dominated by the heterogeneous AHN (low mast cell burden, presence of additional mutations) with a better median OS of 4.5 years. We conclude that (i) in MCL, negativity for D816V is a relevant prognostic factor and (ii) PSS fail to correctly classify D816Vneg. patients.

Publisher

MDPI AG

Reference34 articles.

1. Systemic mastocytosis in 342 consecutive adults: Survival studies and prognostic factors;Lim;Blood,2009

2. Stress, Depression, and Dementia Contribute to Neurodegeneration;Bellomo;Eur. J. Neurodegener. Dis.,2023

3. The Impact of Mast Cells in Neuroimmunology and Cancer;Pandolfi;Eur. J. Neurodegener. Dis.,2023

4. Proposed global prognostic score for systemic mastocytosis: A retrospective prognostic modelling study;Zanotti;Lancet Haematol.,2021

5. Mayo alliance prognostic system for mastocytosis: Clinical and hybrid clinical-molecular models;Pardanani;Blood Adv,2018

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3