前期自体干细胞移植（ASCT）是新诊断的多发性骨髓瘤（MM）患者的标准治疗方法。然而，复发是普遍存在的，并且 ASCT 后与治疗相关的骨髓肿瘤 (t-MN) 通常与不良预后相关。我们假设外周血干细胞 (PBSC) 中异常骨髓祖细胞和免疫效应细胞 (IEC) 的富集与 t-MN 复发和/或发展的较高风险相关。我们对 54 名接受 ASCT 的 MM 患者的 PBSC 进行了全面的骨髓和淋巴免疫表型分析。 ASCT 的中位无进展 (PFS)、无髓样肿瘤 (MNFS) 和总生存 (OS) 分别为 49.6 个月（95% CI：39.5-未达到）、59.7 个月（95% CI：55-74）、和 75.6 个月（95% CI：62-105）。骨髓祖细胞上 CD7 和 HLA-DR 的异常表达与较差的 PFS、MNFS 和 OS 相关。同样，终末分化（CD27/CD28-、CD57/KLRG1）和耗竭（TIGIT/PD-1）T 细胞以及抑制性 NK-T 样（CD159a/CD56）T 细胞的富集与较差的 PFS、MNFS 相关和移植后操作系统。我们对异常骨髓和 IEC 表型的观察甚至在 ASCT 和维持治疗之前就存在，表明 t-MN 的早期易感性和 MM 的较差结果，并且有可能指导未来治疗方式的排序。© 2023。Springer Nature Limited。

Upfront autologous stem cell transplant (ASCT) is the standard of care for newly diagnosed multiple myeloma (MM) patients. However, relapse is ubiquitous and therapy-related myeloid neoplasms (t-MN) post-ASCT are commonly associated with poor outcomes. We hypothesized that the enrichment of abnormal myeloid progenitors and immune effector cells (IEC) in the peripheral blood stem cells (PBSCs) is associated with a higher risk of relapse and/or development of t-MN. We performed a comprehensive myeloid and lymphoid immunophenotyping on PBSCs from 54 patients with MM who underwent ASCT. Median progression-free (PFS), myeloid neoplasm-free (MNFS), and overall survival (OS) from ASCT were 49.6 months (95% CI: 39.5-Not Reached), 59.7 months (95% CI: 55-74), and 75.6 months (95% CI: 62-105), respectively. Abnormal expression of CD7 and HLA-DR on the myeloid progenitor cells was associated with an inferior PFS, MNFS, and OS. Similarly, enrichment of terminally differentiated (CD27/CD28-, CD57/KLRG1+) and exhausted (TIGIT/PD-1+) T-cells, and inhibitory NK-T like (CD159a+/CD56+) T-cells was associated with inferior PFS, MNFS, and OS post-transplant. Our observation of abnormal myeloid and IEC phenotype being present even before ASCT and maintenance therapy suggests an early predisposition to t-MN and inferior outcomes for MM, and has the potential to guide sequencing of future treatment modalities.© 2023. Springer Nature Limited.