Jacobsohn David A, Duerst Reggie, Tse William, Kletzel Morris
Division of Hematology/Oncology/Transplant, Department of Pediatrics, Children's Memorial Hospital, Northwestern University, Feinberg School of Medicine, Chicago, IL 60614, USA.
Lancet. 2004;364(9429):156-62. doi: 10.1016/S0140-6736(04)16628-2.
Transplantation of allogeneic haemopoietic stem cells can cure several non-malignant disorders in children. Transplantation with reduced intensity preparation might achieve the same goals but with less toxicity. We undertook a pilot study to determine engraftment rates, kinetics of engraftment, toxicity, and acute graft-versus-host disease (GVHD) associated with a uniform reduced intensity haemopoietic stem-cell transplant (HSCT) regimen for children with non-malignant diseases.
We studied 13 paediatric patients with non-malignant disorders who underwent reduced intensity HSCT at Children's Memorial Hospital from January, 2000, to February, 2004. Stem-cell sources included unrelated donor, matched-sibling peripheral blood stem cells, and unrelated cord blood. A uniform preparative regimen was used, consisting of fludarabine, busulfan, and anti-thymocyte globulin. Major endpoints were engraftment, transplant-related mortality at day 100, short-term toxicities, and incidence of acute GVHD.
72% of evaluable patients achieved full donor engraftment. There was rapid reconstitution of platelets (median 13.5 days) and neutrophils (median 18 days). Short-term toxicities were minimal, as seen by a median length of hospital stay of 7 days (between days 0-100). Incidence of grade II-IV acute GVHD was 8%. Two patients died before day 100 from underlying disease and viral infection, respectively (day 100 transplant-related mortality of 15%). The 1-year overall survival was 84% (95% CI 64-100). Most patients with immunodeficiencies and metabolic disorders had excellent donor engraftment and disease resolution or stabilisation, but most of those with haemoglobinopathies rejected their graft.
This reduced intensity regimen followed by HSCT provides a good alternative to myeloablative HSCT for children with non-malignant disorders, except for haemoglobinopathies, in which engraftment is poor. Even patients with unrelated donor haemopoietic stem-cell transplants had adequate engraftment with acceptable toxicities.
同种异体造血干细胞移植可治愈儿童的多种非恶性疾病。采用降低强度预处理的移植可能达到相同目标，但毒性较小。我们开展了一项试点研究，以确定与针对非恶性疾病儿童的统一降低强度造血干细胞移植（HSCT）方案相关的植入率、植入动力学、毒性及急性移植物抗宿主病（GVHD）情况。
我们研究了2000年1月至2004年2月在儿童纪念医院接受降低强度HSCT的13例患有非恶性疾病的儿科患者。干细胞来源包括无关供者、匹配同胞外周血干细胞及无关脐血。采用了由氟达拉滨、白消安和抗胸腺细胞球蛋白组成的统一预处理方案。主要终点为植入、第100天的移植相关死亡率、短期毒性及急性GVHD的发生率。
72%的可评估患者实现了完全供者植入。血小板（中位时间13.5天）和中性粒细胞（中位时间18天）迅速重建。短期毒性极小，中位住院时间为7天（第0 - 100天之间）。II - IV级急性GVHD的发生率为8%。两名患者分别在第100天前因基础疾病和病毒感染死亡（第100天的移植相关死亡率为15%）。1年总生存率为84%（95%可信区间64 - 100）。大多数免疫缺陷和代谢紊乱患者有良好的供者植入及疾病缓解或稳定，但大多数血红蛋白病患者排斥其移植物。
这种降低强度方案后进行HSCT为非恶性疾病儿童提供了一种除血红蛋白病（其植入不佳）外的清髓性HSCT的良好替代方案。即使是接受无关供者造血干细胞移植的患者也有足够的植入且毒性可接受。
