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.

造血细胞中的嵌合染色体改变 （mCA） 会增加死亡率以及血液系统癌症和感染的风险。我们调查了 976 例接受大剂量化疗和自体干细胞支持 （ASCT） 的多发性骨髓瘤患者的 mCAs 景观及其临床后果，中位随访时间为 6.4 年。在 158 例患者 （16.2%） 的干细胞收获产物中检测到 mCAs。在 60 例患者 （6.1%） 中发现常染色体畸变，并影响所有染色体。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 mCAs 携带者和非携带者之间的总生存期和进展相似。相比之下，X 染色体缺失的女性患者总生存期更长（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），移植后反应更好 （完全缓解程度 （CR） 或非常好的部分缓解 （VGPR））。这种实质性影响的原因尚不清楚。此外，在少数具有多种 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。多种 mCA 的总生存期较差 （a.a. HR 2.0,95% CI 1.02-3.84;p = 0.04）和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的。