造血细胞中的镶嵌染色体改变（mCA）会增加死亡率以及血液癌症和感染的风险。我们调查了 976 名接受高剂量化疗和自体干细胞支持 (ASCT) 的多发性骨髓瘤患者的 mCA 情况及其临床后果，中位随访时间为 6.4 年。在 158 名患者 (16.2%) 的干细胞收获产物中检测到 mCA。 60 名患者 (6.1%) 发现常染色体畸变，影响所有染色体。 51 名女性（12.7%）发现 X 染色体缺失，55 名男性（9.6%）发现 Y 染色体缺失。常染色体 mCA 携带者和非携带者的总体生存率和进展相似。相比之下，X染色体缺失的女性患者总体生存期较长（年龄调整[a.a.] HR 0.54，95% CI 0.32-0.93，p = 0.02），进展风险较低（a.a. HR 0.55，95% CI 0.35） -0.87；p = 0.01），以及更好的移植后反应（更高程度的完全反应（CR）或非常好的部分反应（VGPR））。造成这种重大影响的原因尚不清楚。此外，在少数患有多种 mCA 的患者（n = 12 名患者）中，通过 mCA 分析证实了干细胞产品中的骨髓瘤克隆。多个 mCA 导致总体生存率较差（a.a. HR 2.0，95% CI 1.02-3.84；p = 0.04），且骨髓瘤进展风险较高（a.a. HR 3.36，95% CI 1.67-6.81；p < 0.001），推测这是由疑似骨髓瘤污染物驱动。© 2024。作者。

Mosaic chromosomal alterations (mCAs) in hematopoietic cells increase mortality and risk of hematological cancers and infections. We investigated the landscape of mCAs and their clinical consequences in 976 patients with multiple myeloma undergoing high-dose chemotherapy and autologous stem cell support (ASCT) with median 6.4 years of follow-up. mCAs were detected in the stem cell harvest product of 158 patients (16.2%). Autosomal aberrations were found in 60 patients (6.1%) and affected all chromosomes. Loss of chromosome X was found in 51 females (12.7%) and loss of chromosome Y in 55 males (9.6%). Overall survival and progression were similar between carriers of autosomal mCAs and non-carriers. In contrast, female patients with loss of the X chromosome had longer overall survival (age-adjusted[a.a.] HR 0.54, 95% CI 0.32-0.93, p = 0.02), lower risk of progression (a.a. HR 0.55, 95% CI 0.35-0.87; p = 0.01), and better post-transplant response (higher degree of complete response (CR) or very good partial response (VGPR)). The reason for this substantial effect is unknown. Additionally, myeloma clones in the stem cell product was confirmed by mCA analysis in the few patients with multiple mCAs (n = 12 patients). Multiple mCAs conferred inferior overall survival (a.a. HR 2.0, 95% CI 1.02-3.84; p = 0.04) and higher risk of myeloma progression (a.a. HR 3.36, 95% CI 1.67-6.81; p < 0.001), which is presumed to be driven by suspected myeloma contaminants.© 2024. The Author(s).