Impact of high-molecular-risk mutations on transplantation outcomes in patients with myelofibrosis Journal Article
| Authors: | Tamari, R.; Rapaport, F.; Zhang, N.; McNamara, C.; Kuykendall, A.; Sallman, D. A.; Komrokji, R.; Arruda, A.; Najfeld, V.; Sandy, L.; Medina, J.; Litvin, R.; Famulare, C. A.; Patel, M. A.; Maloy, M.; Castro-Malaspina, H.; Giralt, S. A.; Weinberg, R. S.; Mascarenhas, J. O.; Mesa, R.; Rondelli, D.; Dueck, A. C.; Levine, R. L.; Gupta, V.; Hoffman, R.; Rampal, R. K. |
| Article Title: | Impact of high-molecular-risk mutations on transplantation outcomes in patients with myelofibrosis |
| Abstract: | Mutational profiling has demonstrated utility in predicting the likelihood of disease progression in patients with myelofibrosis (MF). However, there is limited data regarding the prognostic utility of genetic profiling in MF patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT). We performed high-throughput sequencing of 585 genes on pre-transplant samples from 101 patients with MF who underwent allo-HCT and evaluated the association of mutations and clinical variables with transplantation outcomes. Overall survival (OS) at 5 years post-transplantation was 52%, and relapse-free survival (RFS) was 51.1 % for this cohort. Nonrelapse mortality (NRM) accounted for most deaths. Patient's age, donor's age, donor type, and Dynamic International Prognostic Scoring System score at diagnosis did not predict for outcomes. Mutations known to be associated with increased risk of disease progression, such as ASXL1, SRSF2, IDH1/2, EZH2, and TP53, did not impact OS or RFS. The presence of U2AF1 (P = .007) or DNMT3A (P = .034) mutations was associated with worse OS. A Mutation-Enhanced International Prognostic Scoring System 70 score was available for 80 patients (79%), and there were no differences in outcomes between patients with high risk scores and those with intermediate and low risk scores. Collectively, these data identify mutational predictors of outcome in MF patients undergoing allo-HCT. These genetic biomarkers in conjunction with clinical variables may have important utility in guiding transplantation decision making. © 2019 |
| Keywords: | adult; human tissue; aged; myelofibrosis; gene mutation; major clinical study; overall survival; janus kinase 2; mortality; outcome assessment; preoperative evaluation; gene; cohort analysis; genetic association; relapse; stem cell transplantation; retrospective study; protein p53; high risk patient; myeloablative conditioning; reduced intensity conditioning; allogeneic hematopoietic stem cell transplantation; genetic risk; disease exacerbation; recurrence free survival; stat protein; dna methyltransferase 3a; intermediate risk patient; asxl1 gene; transcription factor ezh2; isocitrate dehydrogenase 1; survival prediction; low risk patient; high throughput sequencing; international prognostic scoring system; isocitrate dehydrogenase 2; human; male; female; article; sf3b1 gene; srsf2 gene; molecular mutations; kmt2c gene; u2af1 gene |
| Journal Title: | Biology of Blood and Marrow Transplantation |
| Volume: | 25 |
| Issue: | 6 |
| ISSN: | 1083-8791 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2019-06-01 |
| Start Page: | 1142 |
| End Page: | 1151 |
| Language: | English |
| DOI: | 10.1016/j.bbmt.2019.01.002 |
| PUBMED: | 30625392 |
| PROVIDER: | scopus |
| PMCID: | PMC6918823 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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