Department of Pediatrics, Washington University in St. Louis, Missouri.
Blood/Marrow Transplantation and Immunology, Children's National Medical Center, District of Columbia.
Pediatr Blood Cancer. 2015 Jul;62(7):1270-6. doi: 10.1002/pbc.25458. Epub 2015 Mar 8.
Hematopoietic cell transplantation (HCT) is curative in patients with severe aplastic anemia (SAA). HCT is considered at presentation when a HLA-matched related donor (MRD) is available and has a high success rate. Unrelated donor (URD) transplants are typically undertaken if immunosuppressive therapy fails. Increased toxicity and graft rejection are often encountered in this setting.
We report a prospective multi-center trial of HCT in 17 children with SAA following novel reduced intensity conditioning with alemtuzumab, fludarabine and melphalan, and the best available donor. Nine were URD transplants matched at 7-8/8 loci, and performed following failure of immune suppression. Median follow up was 61 months (range 6-128).
All patients engrafted. Estimated 5 year event-free and overall-survival was 88% (95%CI 65.7-96.7). Five year overall survival for MRD and URD transplants was 100% and 78% (95%CI 45-93.6) respectively. Median times to neutrophil and platelet engraftment was 14 (range 10-27) and 23.5 (range 11-65) days respectively. Treatment related mortality was 12%. The incidence of grade II-IV and III-IV acute graft-versus-host disease was 29% and 18% respectively. At two years, all but one patient discontinued immunosuppression successfully. Laboratory measures of immune reconstitution normalized at one year and infection rates were low in the latter part of the first year.
HCT using this RIC approach was well tolerated and successful in achieving donor engraftment and early immune reconstitution with good quality of life free of immune suppression. Children with SAA can be successfully transplanted using alemtuzumab based conditioning.
造血细胞移植（HCT）可治愈严重再生障碍性贫血（SAA）患者。当有 HLA 匹配的相关供体（MRD）且成功率高时，可在出现时考虑 HCT。如果免疫抑制治疗失败，通常会进行无关供体（URD）移植。在此情况下，通常会遇到毒性增加和移植物排斥。
我们报告了一项使用阿仑单抗、氟达拉滨和马法兰进行新型低强度预处理后，对 17 例 SAA 儿童进行 HCT 的前瞻性多中心试验，并采用最佳可用供体。9 例为 URD 移植，在免疫抑制治疗失败后，与 7-8/8 个位点相匹配。中位随访时间为 61 个月（范围 6-128）。
所有患者均植入。估计 5 年无事件生存率和总生存率分别为 88%（95%CI 65.7-96.7）。MRD 和 URD 移植的 5 年总生存率分别为 100%和 78%（95%CI 45-93.6）。中性粒细胞和血小板植入的中位时间分别为 14 天（范围 10-27）和 23.5 天（范围 11-65）。治疗相关死亡率为 12%。2 级-4 级和 3 级-4 级急性移植物抗宿主病的发生率分别为 29%和 18%。在两年时，除 1 例患者外，所有患者均成功停用免疫抑制剂。在第一年的后期，免疫重建的实验室指标恢复正常，感染率较低。
采用这种 RIC 方法的 HCT 耐受性良好，成功实现了供体植入和早期免疫重建，生活质量良好，无需免疫抑制。可成功使用基于阿仑单抗的预处理对 SAA 患儿进行移植。
