Kostopoulos Ioannis V, Eleutherakis-Papaiakovou Evangelos, Rousakis Pantelis, Ntanasis-Stathopoulos Ioannis, Panteli Chrysanthi, Orologas-Stavrou Nikolaos, Kanellias Nikolaos, Malandrakis Panagiotis, Liacos Christine-Ivy, Papaioannou Nikos E, Papanota Aristea-Maria, Migkou Magdalini, Fotiou Despina, Gavriatopoulou Maria, Angelis Nikolaos V, Kastritis Efstathios, Dimopoulos Meletios-Athanasios, Tsitsilonis Ourania E, Terpos Evangelos
Department of Biology, School of Science, National and Kapodistrian University of Athens, 15784 Athens, Greece.
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece.
Cancers (Basel). 2021 Aug 11;13(16):4047. doi: 10.3390/cancers13164047.
High-dose chemotherapy with autologous stem cell support (ASCT) is the standard of care for eligible newly diagnosed Multiple Myeloma (MM) patients. Stem cell graft contamination by aberrant plasma cells (APCs) has been considered a possible predictive marker of subsequent clinical outcome, but the limited reports to date present unclear conclusions. We prospectively estimated the frequency of graft contamination using highly sensitive next-generation flow cytometry and evaluated its clinical impact in 199 myeloma patients who underwent an ASCT. Contamination (con+) was detected in 79/199 patients at a median level 2 × 10. Its presence and levels were correlated with response to induction treatment, with 94%, 71% and 43% achieving CR, VGPR and PR, respectively. Importantly, con+ grafts conferred 2-fold and 2.8-fold higher patient-risk of not achieving or delaying reaching CR (4 vs. 11 months) and MRD negativity (5 vs. 18 months) post ASCT, respectively. Our data also provide evidence of a potentially skewed bone marrow (BM) reconstitution due to unpurged grafts, since con+ derived BM had significantly higher prevalence of memory B cells. These data, together with the absence of significant associations with baseline clinical features, highlight graft contamination as a potential biomarker with independent prognostic value for deeper responses, including MRD negativity. Longer follow-up will reveal if this corresponds to PFS or OS advantage.
大剂量化疗联合自体干细胞支持（ASCT）是符合条件的新诊断多发性骨髓瘤（MM）患者的标准治疗方法。异常浆细胞（APC）对干细胞移植物的污染一直被认为是后续临床结果的一个可能预测标志物，但迄今为止有限的报告得出的结论并不明确。我们使用高灵敏度的新一代流式细胞术前瞻性地估计了移植物污染的频率，并评估了其对199例接受ASCT的骨髓瘤患者的临床影响。在199例患者中的79例检测到污染（con+），中位水平为2×10。其存在和水平与诱导治疗反应相关，分别有94%、71%和43%的患者达到完全缓解（CR）、非常好的部分缓解（VGPR）和部分缓解（PR）。重要的是，con+移植物使患者在ASCT后未达到或延迟达到CR（4个月对11个月）和微小残留病阴性（5个月对18个月）的风险分别高出2倍和2.8倍。我们的数据还提供了由于未净化的移植物导致骨髓（BM）重建可能存在偏差的证据，因为con+来源的BM中记忆B细胞的患病率显著更高。这些数据，连同与基线临床特征无显著关联，突出了移植物污染作为一种潜在生物标志物，对包括微小残留病阴性在内的更深层次反应具有独立的预后价值。更长时间的随访将揭示这是否对应于无进展生存期（PFS）或总生存期（OS）优势。
