TY - JOUR
T1 - GIPSS
T2 - Genetically inspired prognostic scoring system for primary myelofibrosis
AU - Tefferi, Ayalew
AU - Guglielmelli, Paola
AU - Nicolosi, Maura
AU - Mannelli, Francesco
AU - Mudireddy, Mythri
AU - Bartalucci, Niccolo
AU - Finke, Christy M.
AU - Lasho, Terra L.
AU - Hanson, Curtis A.
AU - Ketterling, Rhett P.
AU - Begna, Kebede H.
AU - Gangat, Naseema
AU - Pardanani, Animesh
AU - Vannucchi, Alessandro M.
N1 - Funding Information:
Acknowledgements Mayo Clinic funding was provided by the Henry J. Predolin foundation grant (Madison, WI, USA). The University of Florence funding was provided by a grant from the Associazione Italiana per la Ricera sul Cancro (AIRC; Milan, Italy), Special Program Molecular Clinical Oncology 5 × 1000 to AIRC-Gruppo Italiano Malattie Mieloproliferative (AGIMM) project no. 1005. Supported also by a Progetto Ministero della Salute GR-2011-02352109 to PG.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/7/1
Y1 - 2018/7/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41375-018-0107-z
DO - 10.1038/s41375-018-0107-z
M3 - Article
C2 - 29654267
AN - SCOPUS:85045290065
VL - 32
SP - 1631
EP - 1642
JO - Leukemia
JF - Leukemia
SN - 0887-6924
IS - 7
ER -