Impact of High-Molecular-Risk Mutations on Transplantation Outcomes in Patients with Myelofibrosis

Roni Tamari, Franck Rapaport, Nan Zhang, Caroline McNamara, Andrew Kuykendall, David A. Sallman, Rami Komrokji, Andrea Arruda, Vesna Najfeld, Lonette Sandy, Juan Medina, Rivka Litvin, Christopher A. Famulare, Minal A. Patel, Molly Maloy, Hugo Castro-Malaspina, Sergio A. Giralt, Rona S. Weinberg, John O. Mascarenhas, Ruben Mesa & 6 others Damiano Rondelli, Amylou Dueck, Ross L. Levine, Vikas Gupta, Ronald Hoffman, Raajit K. Rampal

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1142-1151
Number of pages10
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number6
DOIs
StatePublished - Jun 1 2019

Fingerprint

Primary Myelofibrosis
Transplantation
Mutation
Hematopoietic Stem Cell Transplantation
Survival
Disease Progression
Tissue Donors
Recurrence
Decision Making
Biomarkers
Transplants
Mortality
Genes

Keywords

  • Molecular mutations
  • Myelofibrosis
  • Stem cell transplantation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Tamari, R., Rapaport, F., Zhang, N., McNamara, C., Kuykendall, A., Sallman, D. A., ... Rampal, R. K. (2019). Impact of High-Molecular-Risk Mutations on Transplantation Outcomes in Patients with Myelofibrosis. Biology of Blood and Marrow Transplantation, 25(6), 1142-1151. https://doi.org/10.1016/j.bbmt.2019.01.002

Impact of High-Molecular-Risk Mutations on Transplantation Outcomes in Patients with Myelofibrosis. / Tamari, Roni; Rapaport, Franck; Zhang, Nan; McNamara, Caroline; Kuykendall, Andrew; Sallman, David A.; Komrokji, Rami; Arruda, Andrea; Najfeld, Vesna; Sandy, Lonette; Medina, Juan; Litvin, Rivka; Famulare, Christopher A.; Patel, Minal A.; Maloy, Molly; Castro-Malaspina, Hugo; Giralt, Sergio A.; Weinberg, Rona S.; Mascarenhas, John O.; Mesa, Ruben; Rondelli, Damiano; Dueck, Amylou; Levine, Ross L.; Gupta, Vikas; Hoffman, Ronald; Rampal, Raajit K.

In: Biology of Blood and Marrow Transplantation, Vol. 25, No. 6, 01.06.2019, p. 1142-1151.

Research output: Contribution to journalArticle

Tamari, R, Rapaport, F, Zhang, N, McNamara, C, Kuykendall, A, Sallman, DA, Komrokji, R, Arruda, A, Najfeld, V, Sandy, L, Medina, J, Litvin, R, Famulare, CA, Patel, MA, Maloy, M, Castro-Malaspina, H, Giralt, SA, Weinberg, RS, Mascarenhas, JO, Mesa, R, Rondelli, D, Dueck, A, Levine, RL, Gupta, V, Hoffman, R & Rampal, RK 2019, 'Impact of High-Molecular-Risk Mutations on Transplantation Outcomes in Patients with Myelofibrosis', Biology of Blood and Marrow Transplantation, vol. 25, no. 6, pp. 1142-1151. https://doi.org/10.1016/j.bbmt.2019.01.002
Tamari, Roni ; Rapaport, Franck ; Zhang, Nan ; McNamara, Caroline ; Kuykendall, Andrew ; Sallman, David A. ; Komrokji, Rami ; Arruda, Andrea ; Najfeld, Vesna ; Sandy, Lonette ; Medina, Juan ; Litvin, Rivka ; Famulare, Christopher A. ; Patel, Minal A. ; Maloy, Molly ; Castro-Malaspina, Hugo ; Giralt, Sergio A. ; Weinberg, Rona S. ; Mascarenhas, John O. ; Mesa, Ruben ; Rondelli, Damiano ; Dueck, Amylou ; Levine, Ross L. ; Gupta, Vikas ; Hoffman, Ronald ; Rampal, Raajit K. / Impact of High-Molecular-Risk Mutations on Transplantation Outcomes in Patients with Myelofibrosis. In: Biology of Blood and Marrow Transplantation. 2019 ; Vol. 25, No. 6. pp. 1142-1151.
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AU - Arruda, Andrea

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AU - Weinberg, Rona S.

AU - Mascarenhas, John O.

AU - Mesa, Ruben

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AU - Dueck, Amylou

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