Supplementary Material for: Minimal clonal plasma cell contamination of peripheral stem cell grafts have an adverse prognostic impact in patients with multiple myeloma undergoing autologous transplantation

Introduction The significance of autografts' contamination by clonal plasma cells on clinical outcome in newly diagnosed multiple myeloma remains controversial. Methods We retrospectively reviewed the clinical and laboratory data of newly diagnosed multiple myeloma (NDMM) patients who underwent autologous stem cell transplantation (ASCT) and had received graft minimal residual disease (gMRD) examination by multi-color flow cytometry. Results From January 2011 to December 2022, 250 NDMM patients with complete cytogenetic information, gMRD information, and who received autologous stem cell transplantation (ASCT) as consolidation were enrolled. Multi-flow cytometry can achieve a median detection sensitivity of 0.004%, and gMRD positivity was 12.4% at a median level of 0.0160% (IQR, 0.0049%, 0.05394%). Its presence was correlated with response to induction treatment, with percentages of 2.65%, 12.94%, 28.89%, and 57.14% of patients achieving complete response, very good partial response, partial response, and minimal response/stable disease, respectively. gMRD (+) patients had a higher risk of not achieving bone marrow MRD negativity post-ASCT. After a median follow-up of 33.5 months for the whole cohort, patients in the gMRD (+) group had significantly worse PFS than those in the gMRD (-) group did (34.8 vs. 65.0 months, P = 0.001). Multivariable analysis revealed that gMRD (-) was independently predictive of better PFS (HR 0.464, 95%CI: 0.274-0.785, P = 0.004). We found the significance of gMRD on PFS was in high-risk subgroups and in patients who achieved ≤ partial response prior to ASCT. Conclusions In conclusion, gMRD (+) was an independent risk factor for inferior progression-free survival, with the impact primarily affecting high-risk groups and patients who achieved ≤ partial response before ASCT.引言：初诊多发性骨髓瘤患者自体移植物被克隆性浆细胞污染对临床结局的意义目前仍存在争议。 方法：本研究回顾性分析了初诊多发性骨髓瘤（Newly Diagnosed Multiple Myeloma, NDMM）患者的临床及实验室资料，这些患者均接受了自体造血干细胞移植（autologous stem cell transplantation, ASCT），且通过多色流式细胞术（multi-color flow cytometry）完成了移植物微小残留病（graft minimal residual disease, gMRD）检测。 结果：2011年1月至2022年12月，共纳入250例具备完整细胞遗传学资料、gMRD资料且以自体造血干细胞移植（ASCT）作为巩固治疗的NDMM患者。多色流式细胞术的中位检测灵敏度可达0.004%，gMRD阳性率为12.4%，中位水平为0.0160%（四分位间距IQR：0.0049%~0.05394%）。gMRD阳性与诱导治疗疗效相关：达到完全缓解（complete response, CR）、非常好的部分缓解（very good partial response, VGPR）、部分缓解（partial response, PR）以及最小缓解/疾病稳定（minimal response/stable disease, MR/SD）的患者中，gMRD阳性率分别为2.65%、12.94%、28.89%与57.14%。gMRD阳性患者在自体造血干细胞移植后更难达到骨髓MRD阴性状态。全队列中位随访时长为33.5个月，gMRD阳性组患者的无进展生存期（Progression-Free Survival, PFS）显著差于gMRD阴性组（34.8个月 vs 65.0个月，P=0.001）。多变量分析显示，gMRD阴性是更好PFS的独立预测因素（风险比（Hazard Ratio, HR）=0.464，95%置信区间（95% Confidence Interval, 95%CI）：0.274~0.785，P=0.004）。本研究发现，gMRD对PFS的影响主要存在于高危亚组以及自体造血干细胞移植前疗效≤部分缓解的患者中。 结论：综上，gMRD阳性是无进展生存期较差的独立危险因素，其影响主要体现在高危人群以及自体造血干细胞移植前疗效≤部分缓解的患者中。