GIPSS: genetically inspired prognostic scoring system for primary myelofibrosis

• DOI: 10.1038/s41375-018-0107-z
• Publication Date: 2018-04-04T02:00:49Z
• Authors: Ayalew Tefferi; Paola Guglielmelli; Maura Nicolosi; Francesco Mannelli; Mythri Mudireddy; Niccolo Bartalucci; Christy M. Finke; Terra L. Lasho; Curtis A. Hanson; Rhett P. Ketterling; Kebede H. Begna; Naseema Gangat; Animesh Pardanani; Alessandro M. Van...
• Keywords: Adult; Male; Epistasis, Genetic; Middle Aged; Prognosis; Risk Assessment; Survival Analysis; Article; 3. Good health; 03 medical and health sciences; Cell Transformation, Neoplastic; 0302 clinical medicine; Primary Myelofibrosis; Risk Factors; Humans; Female; Genetic Predisposition to Disease; Adult; Aged; Biomarkers; Cell Transformation, Neoplastic; Epistasis, Genetic; Female; Humans; Male; Middle Aged; Primary Myelofibrosis; Prognosis; Risk Assessment; Risk Factors; Survival Analysis; Genetic Association Studies; Genetic Predisposition to Disease; Biomarkers; Genetic Association Studies; Aged

International collaborations over the years have produced a series of prognostic models for primary myelofibrosis (PMF), including the recently unveiled mutation-enhanced international prognostic scoring systems for transplant-age patients (MIPSS70 and MIPSS70-plus). In the current study, we considered the feasibility of a genetically inspired prognostic scoring system (GIPSS) that is exclusively based on genetic markers. Among 641 cytogenetically annotated patients with PMF and informative for previously recognized adverse mutations, multivariable analysis identified "VHR" karyotype, "unfavorable" karyotype, absence of type 1/like CALR mutation and presence of ASXL1, SRSF2, or U2AF1Q157 mutation, as inter-independent predictors of inferior survival; the respective HRs (95% CI) were 3.1 (2.1-4.3), 2.1 (1.6-2.7), 2.1 (1.6-2.9), 1.8 (1.5-2.3), 2.4 (1.9-3.2), and 2.4 (1.7-3.3). Based on HR-weighted risk points, a four-tiered GIPSS model was devised: low (zero points; n = 58), intermediate-1 (1 point; n = 260), intermediate-2 (2 points; n = 192), and high (≥3 points; n = 131); the respective median (5-year) survivals were 26.4 (94%), 8.0 (73%), 4.2 (40%), and 2 (14%) years; the model was internally validated by bootstrapping and its predictive accuracy was shown to be comparable to that of MIPSS70-plus. GIPPS offers a low-complexity prognostic tool for PMF that is solely dependent on genetic risk factors and, thus, forward-looking in its essence.