We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Poor Applicability of Currently Available Prognostic Scoring Systems for Prediction of Outcome in KIT D816V-Negative Advanced Systemic Mastocytosis.
- Authors
Naumann, Nicole; Rudelius, Martina; Lübke, Johannes; Christen, Deborah; Bresser, Jakob; Sotlar, Karl; Metzgeroth, Georgia; Fabarius, Alice; Hofmann, Wolf-Karsten; Panse, Jens; Horny, Hans-Peter; Cross, Nicholas C. P.; Reiter, Andreas; Schwaab, Juliana
- Abstract
Simple Summary: Most patients (>95%) with systemic mastocytosis (SM) carry a mutation in the KIT gene (KIT D816V). Especially aggressive forms of SM are associated with pronounced clinical symptoms, blood count abnormalities, additional mutations in other genes and a shortened survival. Only a small minority of patients with SM have another mutation on position D816 (e.g., D816H) or do not harbor any mutation in KIT, and data on these small subgroups are scarce. The aim of our study was to characterize these rare subgroups: we examined 7 SM patients with either KIT D816H or KIT D816Y and 12 SM patients without any KIT mutation. We found that (a) both groups frequently appear as mast cell leukemia (the most aggressive SM subgroup), (b) those patients cannot be assessed using conventional risk scores, (c) response to treatment is poor and (d) overall survival is worse than in KIT D816V-positive SM. 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.
- Subjects
GENETIC mutation; DNA; ONCOGENES; IMMUNOHISTOCHEMISTRY; MAST cell disease; SEVERITY of illness index; TREATMENT effectiveness; PROTEIN-tyrosine kinases; KAPLAN-Meier estimator; DESCRIPTIVE statistics; POLYMERASE chain reaction; DATA analysis software; OVERALL survival; EVALUATION; SYMPTOMS
- Publication
Cancers, 2024, Vol 16, Issue 3, p593
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers16030593