肿瘤细胞治疗研究
英文原题：Efficacy and Safety of CD34+ Stem Cell Boost for Delayed Hematopoietic Recovery After BCMA Directed CAR T-cell Therapy.
Efficacy and Safety of CD34+ Stem Cell Boost for Delayed Hematopoietic Recovery After BCMA Directed CAR T-cell Therapy.
共有 19 例患者接受了干细胞补充，中位剂量为 2.75×10⁶ CD34+ 细胞/kg（范围 1.76-7.38），在 CAR T 输注后中位 53 天（范围 24-126）给予。
嵌合抗原受体（CAR）T细胞疗法彻底改变了复发/难治性多发性骨髓瘤（RRMM）患者的治疗结局。尽管使用生长因子和血小板生成素（TPO）模拟剂进行支持治疗，近半数患者在CAR-T输注后仍会出现严重且持续的血细胞减少，这已成为RRMM患者面临的重大治疗难题。鉴于既往采用自体CD34+造血干细胞治疗异基因或自体干细胞移植后未植入或延迟植入已取得成功，有必要探索将先前储存的自体干细胞作为细胞补充，用于改善RRMM患者CAR-T后血细胞减少。研究人员回顾性分析2020年7月2日至2023年1月18日期间接受CAR-T治疗后输注先前采集并储存的CD34+干细胞的成年RRMM患者，研究涉及多个中心。补充干细胞的指征由临床医生决定，主要包括血细胞减少及相关并发症。共有19例患者接受干细胞补充，中位剂量为2.75×10⁶ CD34+细胞/kg（范围1.76–7.38），中位输注时间为CAR-T后53天（范围24–126天）。18例（95%）患者在干细胞补充后造血恢复；中性粒细胞、血小板和血红蛋白植入中位时间分别为14天（范围9–39天）、17天（范围12–39天）和23天（范围6–34天）。患者对干细胞补充耐受良好，无人发生输注反应。输注前感染常见且严重，输注后仅1例发生新感染。末次随访时，所有患者均不再需要生长因子、TPO激动剂或输血。自体干细胞补充可有效且安全地促进RRMM患者CAR-T后血细胞减少时的造血恢复，也可作为处理CAR-T后血细胞减少、相关并发症及支持治疗需求的有效挽救措施。
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment outcomes for patients with relapsed refractory multiple myeloma (RRMM). Despite supportive care with growth factors and thrombopoietin (TPO) mimetics, nearly half of the patients experience severe and prolonged cytopenias after CAR T infusion, which have become a major therapeutic challenge for patients with RRMM. Given the successful use of CD34+ autologous hematopoietic stem cells for treatment of non- or delayed engraftment after allogeneic and autologous stem cell transplantations, there is a need to explore the role of previously stored autologous stem cells as a boost for post-CAR T cytopenias in RRMM. We performed a multicenter retrospective analysis of adult patients with RRMM who received previously collected and stored CD34+ stem cell boosts after CAR T-cell therapy between 2 July 2020 and 18 January 2023. Indications for boost were determined per physician discretion and primarily included cytopenias and related complications. Overall, a total of 19 patients received stem cell boost, at a median dose of 2.75 10 6 CD34+ cells/kg (range 1.76-7.38), given at a median of 53 days (range 24-126) after CAR T infusion. Eighteen (95%) patients successfully recovered hematopoiesis after stem cell boost with median time for neutrophil, platelet, and hemoglobin engraftment of 14 (range 9-39), 17 (range 12-39), and 23 (range 6-34) days after the boost, respectively. Stem cell boosts were well tolerated, with no patients experiencing infusion reactions. Although infections were common and severe before stem cell boost, only 1 patient experienced a new infection after boost. All patients had experienced independence from use of growth factors, TPO agonists, and transfusions at the last follow-up. Autologous stem cell boosts can be effectively and safely used to promote hematopoietic recovery for post-CAR T cytopenias in patients with RRMM. Stem cell boosts can be a very effective rescue measure for post-CAR T cytopenias and related complications, as well as supportive care needs.
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