肿瘤细胞治疗研究
英文原题：Clonal Myeloid Dysplasia Following CAR T-Cell Therapy: Chicken or the Egg?
多发性骨髓瘤（MM）以反复复发为特征。
多发性骨髓瘤（MM）以反复复发为特征。因此，患者接受多线治疗，包括烷化剂和免疫调节剂，这些治疗与骨髓增生异常综合征（MDS）等继发性恶性肿瘤相关。抗B细胞成熟抗原（BCMA）CAR-T 细胞（CART）疗法对复发/难治性（R/R）MM患者有效。然而，其长期并发症，尤其是MDS，尚不十分清楚。CART疗法是否导致或促进MDS尚未得到充分研究。在本研究中，我们探讨了MDS与CART疗法之间的因果关系。我们回顾性分析了5例患者在接受CART疗法前后MDS相关形态学和突变变化的患病情况。其中，4例在CART疗法后发生MDS，1例在CART前已存在MDS。4例CART后发生MDS的患者在CART治疗前均未显示MDS形态学改变。然而，这4例患者在CART治疗前及CART治疗后的骨髓中均表现出与MDS相关的分子改变。未观察到新的突变。我们的发现提供了初步证据，提示MM中的抗BCMA CART疗法可能促进已有MDS克隆的扩增，而非导致新克隆的产生。
Multiple myeloma (MM) is characterized by recurrent relapses. Consequently, patients receive multiple therapy lines, including alkylating agents and immune modulators, which have been associated with secondary malignancies such as myelodysplastic syndrome (MDS). Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T cell (CART) therapy is efficacious in patients with relapsed/refractory (R/R) MM. However, the long-term complications, particularly MDS, are not well understood. Whether CART therapy causes or promotes MDS has not been thoroughly investigated. In this study, we explored the causal relationship between MDS and CART therapy. We retrospectively examined the prevalence of MDS-related morphological and mutational changes before and after administration of CART therapy in five patients. Among them, four developed MDS after CART therapy, while one had pre-existing MDS prior to CART. None of the four patients who developed post-CART MDS showed morphological MDS changes prior to CART therapy. However, all four patients exhibited molecular alterations associated with MDS in their pre-CART as well as post-CART therapy bone marrow. No new mutations were observed. Our findings provide initial evidence suggesting that anti-BCMA CART therapy in MM may promote expansion of pre-existing MDS clones rather than causing development of new clones.
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