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<p>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% (<i>n</i> = 23). Low dose CY (120–150&#xa0;mg/kg) was a risk factor for MC (<i>P</i> = 0.0002) and increasing the dosage of fludarabine did not eliminate it. Patients receiving 200&#xa0;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 (<i>P</i> = 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&#xa0;days; <i>P</i> = 0.008). Our study shows that CY + ATG conditioning needs to be intensified to maintain engraftment and 200&#xa0;mg/kg CY + 150&#xa0;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: <a href="https://www.chictr.org.cn">https://www.chictr.org.cn</a>; ChiCTR-1900023509. (Retrospective registration in 2019/5/31).</p>

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Early withdrawal immunosuppression improved mixed chimerism in stem cell transplantation for pediatric aplastic anemia

  • 期刊论文

  • 发表日期：

    2025年5月23日

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  • Xinan Wang,
  • Xia Qin,
  • Chengjuan Luo,
  • Changying Luo,
  • Jianmin Wang,
  • Xiaohang Huang,
  • Qiang Mi,
  • Yuchen Lin,
  • Jing Chen

摘要

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).