Most patients with multiple myeloma (MM) undergoing autologous hematopoietic stem cell transplantation (autoHCT) eventually relapse, perhaps due to the presence of clonal plasma cells (CPC) in the autograft. We conducted a retrospective analysis to evaluate the impact of CPC in the autograft on the outcomes of high-risk chromosomal abnormalities (HRMM) patients undergoing autoHCT between 2008 and 2018. Patients were divided into CPC+ or CPC− in the autograft by next-generation flow cytometry (NGF). There were 75 CPC + autografts (18%) and 341 CPC− (82%). The CPC + group was less likely to achieve MRD-negative complete remission post-transplant (11% vs. 42%; p < 0.001). Median progression free survival (PFS) and overall survival (OS) were (12.8 vs. 32.1 months) and (36.4 vs. 81.2 months) in the CPC + and CPC− groups, respectively (both p < 0.001). Also in the subset of patients with MRD-negative ≥VGPR prior to autoHCT, those with CPC + autografts had inferior PFS (HR 4.21, p = 0.006) and OS (HR 7.04, p = 0.002) compared to CPC-. In multivariable analysis, the degree of CPC positivity in the autograft was independently predictive of worse PFS (HR 1.50, p = 0.001) and OS (HR 1.37, p = 0.001). In conclusion, both the presence and degree of CPC in the autograft were highly predictive of inferior PFS and OS.
大多数接受自体造血干细胞移植(autoHCT)的多发性骨髓瘤(MM)患者最终会复发,这可能与自体移植物中存在克隆性浆细胞(CPC)有关。我们进行了一项回顾性分析,评估2008年至2018年间接受autoHCT的高危染色体异常(HRMM)患者自体移植物中CPC对预后的影响。通过新一代流式细胞术(NGF)将患者按自体移植物中CPC阳性(CPC+)或阴性(CPC−)进行分组。结果显示,75例(18%)为CPC+自体移植物,341例(82%)为CPC−。CPC+组在移植后达到微小残留病阴性完全缓解的比例较低(11% vs. 42%;p<0.001)。CPC+组和CPC−组的中位无进展生存期(PFS)和总生存期(OS)分别为(12.8个月 vs. 32.1个月)和(36.4个月 vs. 81.2个月)(均p<0.001)。即使在autoHCT前达到MRD阴性且缓解程度≥VGPR的患者亚组中,与CPC−相比,CPC+自体移植患者的PFS(风险比4.21,p=0.006)和OS(风险比7.04,p=0.002)也更差。多变量分析显示,自体移植物中CPC阳性程度是PFS(风险比1.50,p=0.001)和OS(风险比1.37,p=0.001)恶化的独立预测因素。总之,自体移植物中CPC的存在及其程度均能高度预测较差的PFS和OS。
Impact of clonal plasma cells in autografts on outcomes in high-risk multiple myeloma patients