Background:Cytogenetic abnormalities and the persistence of minimal residual disease (MRD) following autologous stem cell transplantation (ASCT) are two established prognostically unfavorable biomarkers in multiple myeloma (MM). Previous studies have shown that post-transplant MRD status is a powerful predictor of progression-free survival (PFS) and overall survival (OS). However, the impact of MRD remains poorly characterized in MM patients with high- or ultra-high-risk cytogenetics.Objectives:This study investigated the prognostic value of post-transplant MRD in standard- versus high- and ultra-high-risk MM. To this aim, we performed a retrospective analysis of 137 MM patients who underwent high-dose chemotherapy (HDCT) and ASCT at our institution between January 2019 and December 2021. Cytogenetics were assessed by fluorescence in situ hybridization. High-risk genomic alterations included del(17p), t(4;14), t(14;16), t(14;20), gain(1q), andTP53mutations, with two or more alterations defining the ultra-high-risk category. MRD was assessed in bone marrow aspirates post-ASCT using flow cytometry.Results:Eighty-two (60%) patients were categorized as being at standard risk, forty (29%) as high risk, and fifteen (11%) as ultra-high risk. Median follow-up was 47 months. MRD negativity was achieved in 76 (55%) patients. At 48 months, the overall PFS rate was 61% (72%, 50%, and 32% for the standard-, high-, and ultra-high-risk subgroups, respectively;p= 0.0004), while the OS rate was 85% (89%, 79%, and 80% in standard-, high-, and ultra-high-risk MM patients, respectively;p= 0.1494). Within the standard-risk subgroup, longer PFS was observed for patients achieving MRD negativity (p= 0.0172). High- and ultra-high-risk patients showed no significant differences in PFS when stratified by MRD status, possibly due to prompt progression to MRD positivity.Conclusions:Our results suggest that high- and ultra-high-risk MM patients might benefit from closer response monitoring, including dynamic MRD assessment. Further, high- and ultra-high-risk patients might require a more intensive peri-transplant treatment.
背景：细胞遗传学异常和自体干细胞移植（ASCT）后微小残留病（MRD）持续存在是多发性骨髓瘤（MM）中两个已确立的预后不良生物标志物。既往研究表明，移植后MRD状态是无进展生存期（PFS）和总生存期（OS）的有力预测因子。然而，MRD对具有高危或超高危细胞遗传学特征的MM患者的影响仍不明确。 目的：本研究旨在探讨移植后MRD在标危与高危/超高危MM中的预后价值。为此，我们对2019年1月至2021年12月期间在本机构接受大剂量化疗（HDCT）和ASCT的137例MM患者进行了回顾性分析。细胞遗传学通过荧光原位杂交进行评估。高危基因组改变包括del(17p)、t(4;14)、t(14;16)、t(14;20)、gain(1q)和TP53突变，其中存在两种或以上改变定义为超高危类别。MRD在ASCT后通过流式细胞术检测骨髓穿刺液进行评估。 结果：82例（60%）患者被归类为标危，40例（29%）为高危，15例（11%）为超高危。中位随访时间为47个月。76例（55%）患者达到MRD阴性。在48个月时，总体PFS率为61%（标危、高危和超高危亚组分别为72%、50%和32%；p=0.0004），而OS率为85%（标危、高危和超高危MM患者分别为89%、79%和80%；p=0.1494）。在标危亚组中，达到MRD阴性的患者观察到更长的PFS（p=0.0172）。高危和超高危患者按MRD状态分层时，PFS未见显著差异，可能归因于其迅速进展至MRD阳性。 结论：我们的研究结果表明，高危和超高危MM患者可能受益于更密切的疗效监测，包括动态MRD评估。此外，高危和超高危患者可能需要更加强化的移植围术期治疗。
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