MIPSS70: Mutation-enhanced international prognostic score system for transplantation-age patients with primary myelofibrosis

Paola Guglielmelli, Terra L. Lasho, Giada Rotunno, Mythri Mudireddy, Carmela Mannarelli, Maura Nicolosi, Annalisa Pacilli, Animesh Pardanani, Elisa Rumi, Vittorio Rosti, Curtis A. Hanson, Francesco Mannelli, Rhett P. Ketterling, Naseema Gangat, Alessandro Rambaldi, Francesco Passamonti, Giovanni Barosi, Tiziano Barbui, Mario Cazzola, Alessandro M. VannucchiAyalew Tefferi

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151 Scopus citations

Abstract

Purpose To develop a prognostic system for transplantation-age patients with primary myelofibrosis (PMF) that integrates clinical, cytogenetic, and mutation data. Patients and Methods The study included 805 patients with PMF age ≤ 70 years recruited from multiple Italian centers and the Mayo Clinic (Rochester, MN), forming two independent learning and validation cohorts. A Cox multivariable model was used to select from among a list of 22 variables those that were predictive of overall survival (OS). Integrated clinical and genetic prognostic models with (MIPSS70-plus) or without (MIPSS70) cytogenetic information were developed. Results Multivariable analysis identified the following as significant risk factors for OS: hemoglobin < 100 g/L, leukocytes > 25 × 109/L, platelets< 100 × 109/L, circulating blasts ≥ 2%, bone marrow fibrosis grade ≥ 2, constitutional symptoms, absence of CALR type-1 mutation, presence of high–molecular risk mutation (ie, ASXL1, EZH2, SRSF2, IDH1/2), and presence of two or more high–molecular risk mutations. By assigning hazard ratio (HR)–weighted points to these variables, three risk categories were delineated for the MIPSS70 model; 5-year OS was 95% in low-risk, 70% in intermediate-risk, and 29% in high-risk categories, corresponding to median OS of 27.7 years (95% CI, 22 to 34 years), 7.1 years (95% CI, 6.2 to 8.1 years), and 2.3 years (95% CI, 1.9 to 2.7 years), respectively. In the MIPSS70-plus model, which included cytogenetic information, four risk categories were delineated, with 5-year OS of 91% in low-risk, 66% in intermediate-risk (HR, 3.2; 95% CI, 1.9 to 5.2), 42% in high-risk (HR, 6.4; 95% CI, 4.1 to 10.0), and 7% very high–risk categories (HR, 17.0; 95% CI, 9.8 to 29.2). Both models remained effective after inclusion of older patients in the analysis. Conclusion MIPSS70 and MIPSS70-plus provide complementary systems of risk stratification for transplantation-age patients with PMF and integrate prognostically relevant clinical, cytogenetic, and mutation data.

Original languageEnglish (US)
Pages (from-to)310-318
Number of pages9
JournalJournal of Clinical Oncology
Volume36
Issue number4
DOIs
StatePublished - Feb 1 2018

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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