Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant

Tarek H. Mouhieddine; Adam S. Sperling; Robert Redd; Jihye Park; Matthew Leventhal; Christopher J. Gibson; Salomon Manier; Amin H. Nassar; Marzia Capelletti; Daisy Huynh; Mark Bustoros; Romanos Sklavenitis-Pistofidis; Sabrin Tahri; Kalvis Hornburg; Henry Dumke; Muhieddine M. Itani; Cody J. Boehner; Chia Jen Liu; Saud H. AlDubayan; Brendan Reardon; Eliezer M. Van Allen; Jonathan J. Keats; Chip Stewart; Shaadi Mehr; Daniel Auclair; Robert L. Schlossman; Nikhil C. Munshi; Kenneth C. Anderson; David P. Steensma; Jacob P. Laubach; Paul G. Richardson; Jerome Ritz; Benjamin L. Ebert; Robert J. Soiffer; Lorenzo Trippa; Gad Getz; Donna S. Neuberg; Irene M. Ghobrial

doi:10.1038/s41467-020-16805-5

Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant

Tarek H. Mouhieddine, Adam S. Sperling, Robert Redd, Jihye Park, Matthew Leventhal, Christopher J. Gibson, Salomon Manier, Amin H. Nassar, Marzia Capelletti, Daisy Huynh, Mark Bustoros, Romanos Sklavenitis-Pistofidis, Sabrin Tahri, Kalvis Hornburg, Henry Dumke, Muhieddine M. Itani, Cody J. Boehner, Chia Jen Liu, Saud H. AlDubayan, Brendan ReardonEliezer M. Van Allen, Jonathan J. Keats, Chip Stewart, Shaadi Mehr, Daniel Auclair, Robert L. Schlossman, Nikhil C. Munshi, Kenneth C. Anderson, David P. Steensma, Jacob P. Laubach, Paul G. Richardson, Jerome Ritz, Benjamin L. Ebert, Robert J. Soiffer, Lorenzo Trippa, Gad Getz, Donna S. Neuberg, Irene M. Ghobrial^*

^*此作品的通信作者

急重症醫學研究所

研究成果: Article › 同行評審

133 引文斯高帕斯（Scopus）

摘要

Multiple myeloma (MM) is a plasma-cell neoplasm that is treated with high-dose chemotherapy, autologous stem cell transplant (ASCT) and long-term immunomodulatory drug (IMiD) maintenance. The presence of somatic mutations in the peripheral blood is termed clonal hematopoiesis of indeterminate potential (CHIP) and is associated with adverse outcomes. Targeted sequencing of the stem cell product from 629 MM patients treated by ASCT at the Dana-Farber Cancer Institute (2003–2011) detects CHIP in 136/629 patients (21.6%). The most commonly mutated genes are DNMT3A, TET2, TP53, ASXL1 and PPM1D. Twenty-one from fifty-six patients (3.3%) receiving first-line IMiD maintenance develop a therapy-related myeloid neoplasm (TMN). However, regardless of CHIP status, the use of IMiD maintenance associates with improved PFS and OS. In those not receiving IMiD maintenance, CHIP is associated with decreased overall survival (OS) (HR:1.34, p = 0.02) and progression free survival (PFS) (HR:1.45, p < 0.001) due to an increase in MM progression.

原文	English
文章編號	2996
期刊	Nature Communications
卷	11
發行號	1
DOIs	https://doi.org/10.1038/s41467-020-16805-5
出版狀態	Published - 1 12月 2020

存取文件

10.1038/s41467-020-16805-5

其它文件與鏈接

Link to publication in Scopus

引用此

Mouhieddine, T. H., Sperling, A. S., Redd, R., Park, J., Leventhal, M., Gibson, C. J., Manier, S., Nassar, A. H., Capelletti, M., Huynh, D., Bustoros, M., Sklavenitis-Pistofidis, R., Tahri, S., Hornburg, K., Dumke, H., Itani, M. M., Boehner, C. J., Liu, C. J., AlDubayan, S. H., ... Ghobrial, I. M. (2020). Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant. Nature Communications, 11(1), 文章 2996. https://doi.org/10.1038/s41467-020-16805-5

@article{d1532d8ae28b44909acc5f6490b54505,

title = "Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant",

abstract = "Multiple myeloma (MM) is a plasma-cell neoplasm that is treated with high-dose chemotherapy, autologous stem cell transplant (ASCT) and long-term immunomodulatory drug (IMiD) maintenance. The presence of somatic mutations in the peripheral blood is termed clonal hematopoiesis of indeterminate potential (CHIP) and is associated with adverse outcomes. Targeted sequencing of the stem cell product from 629 MM patients treated by ASCT at the Dana-Farber Cancer Institute (2003–2011) detects CHIP in 136/629 patients (21.6%). The most commonly mutated genes are DNMT3A, TET2, TP53, ASXL1 and PPM1D. Twenty-one from fifty-six patients (3.3%) receiving first-line IMiD maintenance develop a therapy-related myeloid neoplasm (TMN). However, regardless of CHIP status, the use of IMiD maintenance associates with improved PFS and OS. In those not receiving IMiD maintenance, CHIP is associated with decreased overall survival (OS) (HR:1.34, p = 0.02) and progression free survival (PFS) (HR:1.45, p < 0.001) due to an increase in MM progression.",

author = "Mouhieddine, {Tarek H.} and Sperling, {Adam S.} and Robert Redd and Jihye Park and Matthew Leventhal and Gibson, {Christopher J.} and Salomon Manier and Nassar, {Amin H.} and Marzia Capelletti and Daisy Huynh and Mark Bustoros and Romanos Sklavenitis-Pistofidis and Sabrin Tahri and Kalvis Hornburg and Henry Dumke and Itani, {Muhieddine M.} and Boehner, {Cody J.} and Liu, {Chia Jen} and AlDubayan, {Saud H.} and Brendan Reardon and {Van Allen}, {Eliezer M.} and Keats, {Jonathan J.} and Chip Stewart and Shaadi Mehr and Daniel Auclair and Schlossman, {Robert L.} and Munshi, {Nikhil C.} and Anderson, {Kenneth C.} and Steensma, {David P.} and Laubach, {Jacob P.} and Richardson, {Paul G.} and Jerome Ritz and Ebert, {Benjamin L.} and Soiffer, {Robert J.} and Lorenzo Trippa and Gad Getz and Neuberg, {Donna S.} and Ghobrial, {Irene M.}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41467-020-16805-5",

language = "English",

volume = "11",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

Mouhieddine, TH, Sperling, AS, Redd, R, Park, J, Leventhal, M, Gibson, CJ, Manier, S, Nassar, AH, Capelletti, M, Huynh, D, Bustoros, M, Sklavenitis-Pistofidis, R, Tahri, S, Hornburg, K, Dumke, H, Itani, MM, Boehner, CJ, Liu, CJ, AlDubayan, SH, Reardon, B, Van Allen, EM, Keats, JJ, Stewart, C, Mehr, S, Auclair, D, Schlossman, RL, Munshi, NC, Anderson, KC, Steensma, DP, Laubach, JP, Richardson, PG, Ritz, J, Ebert, BL, Soiffer, RJ, Trippa, L, Getz, G, Neuberg, DS & Ghobrial, IM 2020, 'Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant', Nature Communications, 卷 11, 編號 1, 2996. https://doi.org/10.1038/s41467-020-16805-5

TY - JOUR

T1 - Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant

AU - Mouhieddine, Tarek H.

AU - Sperling, Adam S.

AU - Redd, Robert

AU - Park, Jihye

AU - Leventhal, Matthew

AU - Gibson, Christopher J.

AU - Manier, Salomon

AU - Nassar, Amin H.

AU - Capelletti, Marzia

AU - Huynh, Daisy

AU - Bustoros, Mark

AU - Sklavenitis-Pistofidis, Romanos

AU - Tahri, Sabrin

AU - Hornburg, Kalvis

AU - Dumke, Henry

AU - Itani, Muhieddine M.

AU - Boehner, Cody J.

AU - Liu, Chia Jen

AU - AlDubayan, Saud H.

AU - Reardon, Brendan

AU - Van Allen, Eliezer M.

AU - Keats, Jonathan J.

AU - Stewart, Chip

AU - Mehr, Shaadi

AU - Auclair, Daniel

AU - Schlossman, Robert L.

AU - Munshi, Nikhil C.

AU - Anderson, Kenneth C.

AU - Steensma, David P.

AU - Laubach, Jacob P.

AU - Richardson, Paul G.

AU - Ritz, Jerome

AU - Ebert, Benjamin L.

AU - Soiffer, Robert J.

AU - Trippa, Lorenzo

AU - Getz, Gad

AU - Neuberg, Donna S.

AU - Ghobrial, Irene M.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - Multiple myeloma (MM) is a plasma-cell neoplasm that is treated with high-dose chemotherapy, autologous stem cell transplant (ASCT) and long-term immunomodulatory drug (IMiD) maintenance. The presence of somatic mutations in the peripheral blood is termed clonal hematopoiesis of indeterminate potential (CHIP) and is associated with adverse outcomes. Targeted sequencing of the stem cell product from 629 MM patients treated by ASCT at the Dana-Farber Cancer Institute (2003–2011) detects CHIP in 136/629 patients (21.6%). The most commonly mutated genes are DNMT3A, TET2, TP53, ASXL1 and PPM1D. Twenty-one from fifty-six patients (3.3%) receiving first-line IMiD maintenance develop a therapy-related myeloid neoplasm (TMN). However, regardless of CHIP status, the use of IMiD maintenance associates with improved PFS and OS. In those not receiving IMiD maintenance, CHIP is associated with decreased overall survival (OS) (HR:1.34, p = 0.02) and progression free survival (PFS) (HR:1.45, p < 0.001) due to an increase in MM progression.

AB - Multiple myeloma (MM) is a plasma-cell neoplasm that is treated with high-dose chemotherapy, autologous stem cell transplant (ASCT) and long-term immunomodulatory drug (IMiD) maintenance. The presence of somatic mutations in the peripheral blood is termed clonal hematopoiesis of indeterminate potential (CHIP) and is associated with adverse outcomes. Targeted sequencing of the stem cell product from 629 MM patients treated by ASCT at the Dana-Farber Cancer Institute (2003–2011) detects CHIP in 136/629 patients (21.6%). The most commonly mutated genes are DNMT3A, TET2, TP53, ASXL1 and PPM1D. Twenty-one from fifty-six patients (3.3%) receiving first-line IMiD maintenance develop a therapy-related myeloid neoplasm (TMN). However, regardless of CHIP status, the use of IMiD maintenance associates with improved PFS and OS. In those not receiving IMiD maintenance, CHIP is associated with decreased overall survival (OS) (HR:1.34, p = 0.02) and progression free survival (PFS) (HR:1.45, p < 0.001) due to an increase in MM progression.

UR - http://www.scopus.com/inward/record.url?scp=85086366630&partnerID=8YFLogxK

U2 - 10.1038/s41467-020-16805-5

DO - 10.1038/s41467-020-16805-5

M3 - Article

C2 - 32533060

AN - SCOPUS:85086366630

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2996

ER -

Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant

摘要

存取文件

其它文件與鏈接

指紋

引用此