Introduction:Despite the approval of novel agents that have significantly improved long-term survival rates for multiple myeloma (MM) patients undergoing autologous stem cell transplant (ASCT), most patients eventually relapse. The failure to achieve or maintain bone marrow (BM) minimal residual disease (MRD) negativity is a recognised adverse prognostic factor for progression-free survival (PFS) and overall survival (OS). Contamination of stem cell apheresis by clonal plasma cells may also affect prognosis, though data remain limited.Methods:We conducted a prospective, single-centre observational study including 100 newly diagnosed MM patients eligible for ASCT and treated with bortezomib-based triplet induction. MRD was assessed both on BM and apheresis samples using multiparameter flow cytometry (MFC-MRD) with a sensitivity of 10−5.Results:Clonal plasma cells were detected in 22 apheresis samples (aMRD+), all of which were associated with BM MRD positivity. Patients with aMRD+ had inferior pre-ASCT responses (≥VGPR: 10% vs. 63%,p= 0.005) and worse post-ASCT BM MRD negativity rates (4% vs. 49%,p= 0.048). After a median follow-up of 52.4 months, aMRD+ was associated with shorter progression-free survival (median 38.5 vs. not reached,p= 0.007) and overall survival (median 60 months vs. not reached,p= 0.003).Conclusions:Contamination of the apheresis product is associated with persistent BM disease and poorer outcomes. Combined MRD assessment in both bone marrow and apheresis may improve risk stratification in MM patients undergoing ASCT.
引言:尽管新型药物的获批显著改善了接受自体干细胞移植(ASCT)的多发性骨髓瘤(MM)患者的长期生存率,但大多数患者最终仍会复发。无法达到或维持骨髓(BM)微小残留病(MRD)阴性状态,已被公认为是影响无进展生存期(PFS)和总生存期(OS)的不良预后因素。干细胞采集物中克隆性浆细胞的污染也可能影响预后,尽管相关数据仍然有限。 方法:我们开展了一项前瞻性、单中心观察性研究,纳入了100例符合ASCT条件且接受基于硼替佐米的三联诱导方案治疗的新诊断MM患者。采用灵敏度为10⁻⁵的多参数流式细胞术(MFC-MRD)对骨髓和干细胞采集物样本进行MRD评估。 结果:在22份干细胞采集物样本中检测到克隆性浆细胞(aMRD+),且均与骨髓MRD阳性相关。aMRD+患者在ASCT前的治疗反应较差(≥非常好的部分缓解率:10% vs. 63%,p=0.005),ASCT后骨髓MRD阴性率也更低(4% vs. 49%,p=0.048)。中位随访52.4个月后,aMRD+与较短的无进展生存期(中位38.5个月 vs. 未达到,p=0.007)和总生存期(中位60个月 vs. 未达到,p=0.003)相关。 结论:干细胞采集物的污染与持续的骨髓疾病及较差的临床结局相关。联合评估骨髓和干细胞采集物的MRD状态,可能有助于改善接受ASCT的MM患者的风险分层。