{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:44:06Z","timestamp":1789015446730,"version":"build-2803163510"},"reference-count":34,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T00:00:00Z","timestamp":1706572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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 &gt;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 &lt; 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.<\/jats:p>","DOI":"10.3390\/cancers16030593","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T11:35:34Z","timestamp":1706614534000},"page":"593","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Poor Applicability of Currently Available Prognostic Scoring Systems for Prediction of Outcome in KIT D816V-Negative Advanced Systemic Mastocytosis"],"prefix":"10.3390","volume":"16","author":[{"given":"Nicole","family":"Naumann","sequence":"first","affiliation":[{"name":"Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Rudelius","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Ludwig-Maximilian-University, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0767-1504","authenticated-orcid":false,"given":"Johannes","family":"L\u00fcbke","sequence":"additional","affiliation":[{"name":"Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Christen","sequence":"additional","affiliation":[{"name":"Department of Oncology, Haematology, Haemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, 52074 Aachen, Germany"},{"name":"Center for Integrated Oncology (CIO), Aachen, Bonn, Cologne, D\u00fcsseldorf (ABCD), 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Bresser","sequence":"additional","affiliation":[{"name":"Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Sotlar","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Salzburg, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Metzgeroth","sequence":"additional","affiliation":[{"name":"Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Fabarius","sequence":"additional","affiliation":[{"name":"Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolf-Karsten","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6316-3112","authenticated-orcid":false,"given":"Jens","family":"Panse","sequence":"additional","affiliation":[{"name":"Department of Oncology, Haematology, Haemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, 52074 Aachen, Germany"},{"name":"Center for Integrated Oncology (CIO), Aachen, Bonn, Cologne, D\u00fcsseldorf (ABCD), 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Peter","family":"Horny","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Ludwig-Maximilian-University, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5481-2555","authenticated-orcid":false,"given":"Nicholas C. P.","family":"Cross","sequence":"additional","affiliation":[{"name":"Wessex Genomics Laboratory Service, Salisbury SP2 8BJ, UK"},{"name":"Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Reiter","sequence":"additional","affiliation":[{"name":"Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9208-5264","authenticated-orcid":false,"given":"Juliana","family":"Schwaab","sequence":"additional","affiliation":[{"name":"Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5727","DOI":"10.1182\/blood-2009-02-205237","article-title":"Systemic mastocytosis in 342 consecutive adults: Survival studies and prognostic factors","volume":"113","author":"Lim","year":"2009","journal-title":"Blood"},{"key":"ref_2","first-page":"15","article-title":"Stress, Depression, and Dementia Contribute to Neurodegeneration","volume":"12","author":"Bellomo","year":"2023","journal-title":"Eur. 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