Mayo alliance prognostic system for mastocytosis: Clinical and hybrid clinical-molecular models

Animesh Pardanani, Sahrish Shah, Francesco Mannelli, Yoseph C. Elala, Paola Guglielmelli, Terra L. Lasho, Mrinal M. Patnaik, Naseema Gangat, Rhett P. Ketterling, Kaaren K. Reichard, Curtis A. Hanson, Alessandro M. Vannucchi, Ayalew Tefferi

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Systemic mastocytosis (SM) is a clinically heterogeneous disease with prognosis chiefly assigned based on World Health Organization (WHO) morphologic subclassification. We assessed the feasibility of developing contemporary risk models for SM based on clinical and integrated clinical-genetics information. Diagnosis of SM was per WHO criteria, and karyotype and next-generation sequencing data were available in a subset of the total 580 patients (median age, 55 years; range, 18-88 years) seen at the Mayo Clinic between 1968 and 2015. Morphologic subcategories were indolent/smoldering in 291 (50%) and "advanced" in 289 (50%): SM with an associated hematological neoplasm in 199, aggressive SM in 85, and mast cell leukemia in 5. Multivariable analysis of clinical variables identified age <60 years, advanced SM, thrombocytopenia >150 × 109/L, anemia below sex-Adjusted normal, and increased alkaline phosphatase (ALP) as independent risk factors for survival; respective hazard ratios (HRs) 95% confidence intervals (95% CIs) were 2.5 (1.9-3.4), 2.7 (1.8-4.0), 2.5 (1.9-3.4), 2.2 (1.6-3.1), and 2.1 (1.5-3.0). In addition, ASXL1 (HR, 4.5; 95% CI, 2.6-7.6), RUNX1 (HR, 4.3; 95% CI, 1.3-10.8), and NRAS (HR, 5.0, 95% CI, 1.5-13.2) mutations were independently associated with inferior survival. Combined clinical, cytogenetic, and molecular risk factor analysis confirmed the independent prognostic contribution of adverse mutations (2.6, 1.6-4.4), advanced SM (4.0, 1.8-10.0), thrombocytopenia (2.8, 1.7-4.5), increased ALP (2.1, 1.2-4.0), and age <60 years (2.2, 1.3-3.6). These data were subsequently used to develop clinical and hybrid clinical-molecular risk models. The current study advances 2 complementary risk models for SM and highlights the independent prognostic contribution of mutations.

Original languageEnglish (US)
Pages (from-to)2964-2972
Number of pages9
JournalBlood Advances
Volume2
Issue number21
DOIs
StatePublished - Nov 13 2018

ASJC Scopus subject areas

  • Hematology

Fingerprint Dive into the research topics of 'Mayo alliance prognostic system for mastocytosis: Clinical and hybrid clinical-molecular models'. Together they form a unique fingerprint.

  • Cite this

    Pardanani, A., Shah, S., Mannelli, F., Elala, Y. C., Guglielmelli, P., Lasho, T. L., Patnaik, M. M., Gangat, N., Ketterling, R. P., Reichard, K. K., Hanson, C. A., Vannucchi, A. M., & Tefferi, A. (2018). Mayo alliance prognostic system for mastocytosis: Clinical and hybrid clinical-molecular models. Blood Advances, 2(21), 2964-2972. https://doi.org/10.1182/bloodadvances.2018026245