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• W2912015014 abstract "Background The Dynamic International Prognostic Scoring System (DIPSS) is commonly applied to predict survival among patients with primary myelofibrosis (PMF) but has been shown to perform less precisely in secondary myelofibrosis (SMF) and after transplantation. Furthermore, the prognostic relevance of mutation profile resulted in the mutation-enhanced IPSS (MIPSS70) in PMF, as well as in a model specific to SMF (MYSEC-PM). We aimed to develop a comprehensive clinical-molecular prognostic scoring system to determine outcome for myelofibrosis undergoing allogeneic stem cell transplantation. Patients and Methods We examined 361 myelofibrosis patients, of whom 260 had PMF and 101 SMF at time of transplantation. A training cohort of 205 patients was used to create a clinical-molecular transplant scoring system (MTSS) predicting survival from Cox models, internally validated by use of bootstrap and cross-validation. Model discrimination was measured by the concordance index (C). The final MTSS was externally validated in a cohort of 156 patients and was furthermore applied to posttransplant non-relapse mortality as a secondary objective. Results Multivariable analysis on 5-year survival identified age ≥57 years, Karnofsky performance status 25 × 109/L at time of transplantation, HLA-mismatched unrelated donor, ASXL1 mutated and CALR-/MPL-unmutated genotype being independent prognostic factors for outcome. The uncorrected concordance index for the final survival model was 0.723 (95% CI, 0.713-0.733), and bias-corrected indices were similar. A weighted score of 2 was assigned to transplantation from an HLA-mismatched unrelated donor and an CALR-/MPL-unmutated genotype, whereas a score of 1 was assigned to older age, leukocytosis, thrombocytopenia, ASXL1 mutation, and poor performance status. The MTSS consisted of four distinct risk groups showing 5-year survival in the validation cohort of 83% (95% CI, 71-95%) for low (score 0-2), 64% (95% CI, 53-75%) for intermediate (score 3-4), 37% (95% CI, 17-57%) for high (score 5), and 22% (95% CI, 4-39%) for very high risk (score >5), respectively (P Conclusion The MTSS integrates clinical, molecular as well as transplant-specific risk factors that independently affected survival. We show here that this internally and externally validated system accurately discriminated different risk for death and may improve counseling compared with currently existing systems, as well as facilitate design of clinical trials in the transplant setting." @default.
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• W2912015014 date "2019-03-01" @default.
• W2912015014 modified "2023-09-27" @default.
• W2912015014 title "Comprehensive Clinical-Molecular Transplant Risk Model for Myelofibrosis Undergoing Allogeneic Stem Cell Transplantation" @default.
• W2912015014 doi "https://doi.org/10.1016/j.bbmt.2018.12.381" @default.
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