Mangkuliguna Ghea, Tehuteru Edi Setiawan, Jonlean Reganedgary, Adrianto Nicholas, Kallista Stella
School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia.
Hematopoietic Stem Cell Transplantation Unit, Indonesia Tzu Chi Hospital, Jakarta, Indonesia.
Clin Exp Pediatr. 2025 Sep;68(9):712-721. doi: 10.3345/cep.2025.00031. Epub 2025 Jul 4.
Allogeneic stem cell transplantation (allo-SCT) and chimeric antigen receptor (CAR) T-cell therapy offer potential complementary benefits.
This study aimed to ascertain whether incorporating consolidative allo-SCT after CAR T-cell therapy can augment the therapeutic outcomes of child and young adult patients with relapsed/refractory hematologic malignancy.
A comprehensive literature search of PubMed, ScienceDirect, Cochrane Library, EBSCOHost, ProQuest, and the grey literature repositories was performed for articles published between May 5, 2014, and May 5, 2024. We included studies reporting consolidative allo-SCT following CAR T-cell therapy for treating hematologic malignancies in subjects aged ≤25 years old. The outcomes of interest were complete remission, survival, relapse, and mortality rates. The estimates were pooled using random-effects meta-analysis. The risk of bias was evaluated using the Newcastle-Ottawa Scale, while the certainty of evidence was assessed using GRADE. This study follows the PRISMA 2020 criteria and is registered in the PROSPERO database (CRD42023433417).
Twelve cohort studies involving 380 patients, primarily those with B-cell acute lymphoblastic leukemia (B-ALL), were included. The CAR T-cell+SCT group showed a trend toward higher complete remission (odds ratio [OR], 2.74; 95% confidence interval [CI], 0.88-8.54; P= 0.08; I2=57%; evidence, very low); lower mortality (OR, 0.58; 95% CI, 0.27-1.27; P=0.17; I2=0%; evidence, low), and decreased relapse (OR, 0.18; 95% CI, 0.06-0.56; P=0.003; I2=41%; evidence, low) rates than those who did not proceed to SCT. In addition, both overall survival and leukemia-free survival rates showed a favorable trend toward the CAR T-cell+SCT group, respectively (hazard ratio, 0.44; 95% CI, 0.25-0.77; P=0.005; I2=0%; evidence, low; and hazard ratio, 0.29; 95% CI, 0.17-0.49; P<0.00001; I2=0%; evidence, low). Common posttransplant toxicities include mild to moderate acute and chronic graft-versus-host diseases.
Although the current level of evidence remains low or very low, allo-SCT following CAR T-cell infusion potentially benefits patient survival. Further clinical studies are required to confirm these findings.
异基因干细胞移植（allo-SCT）和嵌合抗原受体（CAR）T细胞疗法具有潜在的互补优势。
本研究旨在确定在CAR T细胞疗法后进行巩固性allo-SCT是否能提高复发/难治性血液系统恶性肿瘤儿童和年轻成人患者的治疗效果。
对PubMed、ScienceDirect、Cochrane图书馆、EBSCOHost、ProQuest和灰色文献库进行全面文献检索，查找2014年5月5日至2024年5月5日期间发表的文章。我们纳入了报告在年龄≤25岁的受试者中，CAR T细胞疗法后进行巩固性allo-SCT治疗血液系统恶性肿瘤的研究。感兴趣的结局包括完全缓解、生存率、复发率和死亡率。采用随机效应荟萃分析汇总估计值。使用纽卡斯尔-渥太华量表评估偏倚风险，同时使用GRADE评估证据的确定性。本研究遵循PRISMA 2020标准，并已在PROSPERO数据库注册（CRD42023433417）。
纳入了12项队列研究，共380例患者，主要为B细胞急性淋巴细胞白血病（B-ALL）患者。CAR T细胞 + SCT组显示出完全缓解率更高的趋势（优势比[OR]，2.74；95%置信区间[CI]，0.88 - 8.54；P = 0.（此处原文有误，应为0.08）；I² = 57%；证据，极低）；死亡率更低（OR，0.58；95% CI，0.27 - 1.27；P = 0.17；I² = 0%；证据，低），且复发率低于未进行SCT的患者（OR，0.18；95% CI，0.06 - 0.56；P = 0.003；I² = 41%；证据为低）。此外，总生存率和无白血病生存率在CAR T细胞 + SCT组中也分别呈现出有利趋势（风险比，0.44；95% CI，0.25 - 0.77；P = 0.005；I² = 0%；证据，低；以及风险比，0.29；95% CI，0.17 - 0.49；P < 0.00001；I² = 0%；证据，低）。常见的移植后毒性包括轻度至中度的急性和慢性移植物抗宿主病。
尽管目前的证据水平仍然较低或非常低，但CAR T细胞输注后进行allo-SCT可能对患者生存有益。需要进一步的临床研究来证实这些发现。
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