Pillai Asha, Hartford Christine, Wang Chong, Pei Deqing, Yang Jie, Srinivasan Ashok, Triplett Brandon, Dallas Mari, Leung Wing
Department of Oncology, St Jude Children's Research Hospital Memphis, TN, USA.
Pediatr Transplant. 2011 Sep;15(6):628-34. doi: 10.1111/j.1399-3046.2011.01542.x. Epub 2011 Jul 15.
To assess whether a tolerance-induction regimen could be applied for unrelated (MUD) HCT in SAA, we retrospectively reviewed our HCT experience using unmanipulated 10/10 HLA-matched bone marrow grafts from MSD vs. MUD donors. Conditioning was CTX 200 mg/kg (CTX) + rabbit ATG 10 mg/kg (ATG) for MSD (n = 9) and TLI (800 cGy) + CTX/ATG for MUD HCT ( n = 5). Immunoprophylaxis was CSA and short-course MTX. Median patient age was 14.7 yr, median time to HCT 1.5 yr, and median follow-up 3 yr. Outcome measures included EFS, time to engraftment, and cumulative incidence of GVHD (CIN of GVHD) for MSD and MUD cohorts. EFS and stable engraftment rate were 100%. CIN of acute GVHD was: MSD, Grade I-II: 1 (11%), Grade III-IV: 0%; MUD, Grade I-II: 1 (20%), Grade III-IV: 1 (20%). CIN of chronic GVHD was: MSD, limited: 1 (11%), extensive: 0%; MUD, limited: 0%, extensive: 0%. All immunosuppressive-compliant patients successfully weaned immunosuppression. Although in limited patients, our results suggest that immunomodulatory TLI added to backbone CTX/ATG conditioning is a promising option for MUD HCT in SAA patients, which we will examine in a prospective clinical trial.
为评估耐受性诱导方案是否可应用于再生障碍性贫血（SAA）患者的非血缘（MUD）造血干细胞移植（HCT），我们回顾性分析了使用来自匹配无关供者（MSD）与非血缘供者（MUD）未处理的10/10 HLA匹配骨髓移植物进行HCT的经验。对于MSD（n = 9），预处理方案为环磷酰胺（CTX）200 mg/kg + 兔抗胸腺细胞球蛋白（ATG）10 mg/kg；对于MUD HCT（n = 5），预处理方案为全身照射（TLI）（800 cGy）+ CTX/ATG。免疫预防采用环孢素A（CSA）和短疗程甲氨蝶呤（MTX）。患者中位年龄为14.7岁，HCT中位时间为1.5年，中位随访时间为3年。观察指标包括MSD和MUD队列的无事件生存期（EFS）、植入时间以及移植物抗宿主病（GVHD）的累积发生率（CIN of GVHD）。EFS和稳定植入率均为100%。急性GVHD的CIN为：MSD，I-II级：1例（11%），III-IV级：0%；MUD，I-II级：1例（20%），III-IV级：1例（20%）。慢性GVHD的CIN为：MSD，局限性：1例（11%），广泛性：0%；MUD，局限性：0%，广泛性：0%。所有依从免疫抑制治疗的患者均成功停用免疫抑制剂。尽管患者数量有限，但我们的结果表明，在基础CTX/ATG预处理方案中添加免疫调节性TLI是SAA患者MUD HCT的一个有前景的选择，我们将在一项前瞻性临床试验中对此进行研究。
