TY - JOUR
T1 - Impact of High-Molecular-Risk Mutations on Transplantation Outcomes in Patients with Myelofibrosis
AU - Tamari, Roni
AU - Rapaport, Franck
AU - Zhang, Nan
AU - McNamara, Caroline
AU - Kuykendall, Andrew
AU - Sallman, David A.
AU - Komrokji, Rami
AU - Arruda, Andrea
AU - Najfeld, Vesna
AU - Sandy, Lonette
AU - Medina, Juan
AU - Litvin, Rivka
AU - Famulare, Christopher A.
AU - Patel, Minal A.
AU - Maloy, Molly
AU - Castro-Malaspina, Hugo
AU - Giralt, Sergio A.
AU - Weinberg, Rona S.
AU - Mascarenhas, John O.
AU - Mesa, Ruben
AU - Rondelli, Damiano
AU - Dueck, Amylou C.
AU - Levine, Ross L.
AU - Gupta, Vikas
AU - Hoffman, Ronald
AU - Rampal, Raajit K.
N1 - Publisher Copyright:
© 2019
PY - 2019/6
Y1 - 2019/6
N2 - 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.
AB - 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.
KW - Molecular mutations
KW - Myelofibrosis
KW - Stem cell transplantation
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UR - http://www.scopus.com/inward/citedby.url?scp=85063640384&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2019.01.002
DO - 10.1016/j.bbmt.2019.01.002
M3 - Article
C2 - 30625392
AN - SCOPUS:85063640384
SN - 1083-8791
VL - 25
SP - 1142
EP - 1151
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 6
ER -