Wang Xinan, Qin Xia, Luo Chengjuan, Luo Changying, Wang Jianmin, Huang Xiaohang, Mi Qiang, Lin Yuchen, Chen Jing
Department of Hematology and Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai, 200127, CN, China.
Int J Hematol. 2025 May 23. doi: 10.1007/s12185-025-03971-9.
Mixed chimerism occurs frequently with the risk of graft rejection for aplastic anemia patients undergoing matched sibling donor hematopoietic stem cell transplantation in cyclophosphamide (CY) and anti-thymocyte globulin (ATG) conditioning. So far, no one knows how to adjust immunosuppression (IS) during MC. We retrospectively analyzed 87 consecutive pediatric patients. Early withdrawal (EW) IS and donor lymphocyte infusion were attempted to reverse MC. The rate of MC was 26% (n = 23). Low dose CY (120-150 mg/kg) was a risk factor for MC (P = 0.0002) and increasing the dosage of fludarabine did not eliminate it. Patients receiving 200 mg/kg CY had the lowest MC rate (8%) and best 3-year graft-versus-host disease/failure-free survival (GFFS; 95%). Donor chimerism in T cells was more sensitive than that in whole blood (P = 0.001). In 17 patients with early-onset MC, EW IS strategy was helpful in improving complete chimerism (CC) (EW cohort: 63 versus non-EW cohort: 295 days; P = 0.008). Our study shows that CY + ATG conditioning needs to be intensified to maintain engraftment and 200 mg/kg CY + 150 mg/m2 FLU is recommended for basic conditioning. The EW IS strategy should be considered as an important option to improve donor chimerism in early-onset MC. Clinical trial registration: URL: https://www.chictr.org.cn ; ChiCTR-1900023509. (Retrospective registration in 2019/5/31).
对于接受环磷酰胺（CY）和抗胸腺细胞球蛋白（ATG）预处理的再生障碍性贫血患者，在进行同胞全相合造血干细胞移植时，混合嵌合现象频繁出现且存在移植物排斥风险。到目前为止，尚无人知晓如何在混合嵌合期间调整免疫抑制（IS）。我们回顾性分析了87例连续的儿科患者。尝试通过早期停用（EW）IS和供体淋巴细胞输注来逆转混合嵌合。混合嵌合率为26%（n = 23）。低剂量CY（120 - 150 mg/kg）是混合嵌合的一个危险因素（P = 0.0002），增加氟达拉滨剂量并不能消除该危险因素。接受200 mg/kg CY的患者混合嵌合率最低（8%），且3年无移植物抗宿主病/无失败生存率（GFFS）最佳（95%）。T细胞中的供体嵌合比全血中的更敏感（P = 0.001）。在17例早期发生混合嵌合的患者中，EW IS策略有助于提高完全嵌合（CC）（EW组：63天，非EW组：295天；P = 0.008）。我们的研究表明，CY + ATG预处理需要强化以维持植入，建议基础预处理采用200 mg/kg CY + 150 mg/m²氟达拉滨。EW IS策略应被视为改善早期发生混合嵌合时供体嵌合的重要选择。临床试验注册：网址：https://www.chictr.org.cn ；ChiCTR - 1900023509。（2019年5月31日回顾性注册）
