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

被引：128

作者：

Mouhieddine, Tarek H. ^{[1
,2
,3
]}

Sperling, Adam S. ^{[1
,2
]}

Redd, Robert ^{[4
]}

Park, Jihye ^{[1
,3
]}

Leventhal, Matthew ^{[3
]}

Gibson, Christopher J. ^{[1
]}

Manier, Salomon ^{[1
,5
,6
]}

Nassar, Amin H. ^{[1
,7
]}

Capelletti, Marzia ^{[1
]}

Huynh, Daisy ^{[1
]}

Bustoros, Mark ^{[1
,2
,3
]}

Sklavenitis-Pistofidis, Romanos ^{[1
,2
,3
]}

Tahri, Sabrin ^{[1
,2
,3
]}

Hornburg, Kalvis ^{[1
]}

Dumke, Henry ^{[1
]}

Itani, Muhieddine M. ^{[8
]}

Boehner, Cody J. ^{[1
]}

Liu, Chia-Jen ^{[1
]}

AlDubayan, Saud H. ^{[1
]}

Reardon, Brendan ^{[1
]}

Van Allen, Eliezer M. ^{[1
]}

Keats, Jonathan J. ^{[9
]}

Stewart, Chip ^{[4
]}

Mehr, Shaadi ^{[10
]}

Auclair, Daniel ^{[10
]}

Schlossman, Robert L. ^{[1
]}

Munshi, Nikhil C. ^{[1
]}

Anderson, Kenneth C. ^{[1
]}

Steensma, David P. ^{[1
]}

Laubach, Jacob P. ^{[1
]}

Richardson, Paul G. ^{[1
]}

Ritz, Jerome ^{[1
]}

Ebert, Benjamin L. ^{[1
,2
,3
]}

Soiffer, Robert J. ^{[1
]}

Trippa, Lorenzo ^{[1
,11
]}

Getz, Gad ^{[3
,8
]}

Neuberg, Donna S. ^{[4
]}

Ghobrial, Irene M. ^{[1
,2
,3
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[2] Harvard Med Sch, Boston, MA 02115 USA

[3] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[4] Dana Farber Canc Inst, Dept Data Sci, Boston, MA 02115 USA

[5] Univ Lille, Dept Hematol, CHU, F-59000 Lille, France

[6] INSERM UMR S1172, F-59000 Lille, France

[7] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA

[8] Massachusetts Gen Hosp, Boston, MA 02114 USA

[9] Translat Genom Res Inst, Integrated Canc Genom Div, Phoenix, AZ 85004 USA

[10] Multiple Myeloma Res Fdn, Norwalk, CT 06851 USA

[11] Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

关键词：

STEM-CELL TRANSPLANTATION; TP53; MUTATIONS; LENALIDOMIDE MAINTENANCE; RISK; THERAPY; CONTAMINATION; CHEMOTHERAPY; EVOLUTION; DISCOVERY; FRAMEWORK;

D O I：

10.1038/s41467-020-16805-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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. Multiple myeloma (MM) is treated with induction chemotherapy, autologous stem cell transplant (ASCT) and long-term immunomodulatory drug (IMiD) maintenance. Here, the authors show that the presence of clonal haematopoiesis of indeterminate potential (CHIP) at time of ASCT is associated with adverse outcomes in MM patients.

引用

页数：9

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