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.
前期自体干细胞移植（ASCT）是新诊断多发性骨髓瘤（MM）患者的标准治疗方案。然而，复发普遍存在，且ASCT后出现的治疗相关髓系肿瘤（t-MN）通常与不良预后相关。我们假设，外周血干细胞（PBSCs）中异常髓系祖细胞和免疫效应细胞（IEC）的富集与更高的复发风险和/或t-MN发生相关。我们对54例接受ASCT的MM患者的PBSCs进行了全面的髓系和淋巴系免疫表型分析。自ASCT起的中位无进展生存期（PFS）、无髓系肿瘤生存期（MNFS）和总生存期（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）。髓系祖细胞上CD7和HLA-DR的异常表达与较差的PFS、MNFS和OS相关。类似地，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，也与移植后较差的PFS、MNFS和OS相关。我们观察到，即使在ASCT和维持治疗之前就已存在异常的髓系和IEC表型，这表明存在早期发生t-MN和MM预后较差的倾向，这一发现有望指导未来治疗模式的顺序选择。
肿瘤(癌症)患者之家