Cancers (Jan 2024)

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

  • Nicole Naumann,
  • Martina Rudelius,
  • Johannes Lübke,
  • Deborah Christen,
  • Jakob Bresser,
  • Karl Sotlar,
  • Georgia Metzgeroth,
  • Alice Fabarius,
  • Wolf-Karsten Hofmann,
  • Jens Panse,
  • Hans-Peter Horny,
  • Nicholas C. P. Cross,
  • Andreas Reiter,
  • Juliana Schwaab

DOI
https://doi.org/10.3390/cancers16030593
Journal volume & issue
Vol. 16, no. 3
p. 593

Abstract

Read online

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 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.

Keywords