Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant
Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant
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DOI：
10.1038/s41467-020-16805-5
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发表时间：
2020-06-12
影响因子：
16.6
通讯作者：
Ghobrial, Irene M.
中科院分区：
文献类型：
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作者：
Mouhieddine, Tarek H.;Sperling, Adam S.;Ghobrial, Irene M.
多发性骨髓瘤（MM）是一种浆细胞肿瘤，可通过高剂量化疗、自体干细胞移植（ASCT）和长期免疫调节药物（IMiD）维持治疗。外周血中存在体细胞突变被称为不确定潜能的克隆性造血（CHIP），并与不良结局相关。在Dana-Farber癌症研究所（2003-2011），对629例接受ASCT治疗的MM患者的干细胞产物进行靶向测序，在136/629例患者（21.6%）中检测到CHIP。最常见的突变基因是DNMT 3A、TET 2、TP 53、ASXL 1和PPM 1D。接受一线IMiD维持治疗的五十六例患者中有二十一例（3.3%）发生治疗相关性髓系肿瘤（TMN）。然而，无论CHIP状态如何，使用IMiD维持与PFS和OS改善相关。在未接受IMiD维持的患者中，CHIP与总生存期（OS）（HR：1.34，p=0.02）和无进展生存期（PFS）（HR：1.45，p
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