Department of Pediatrics, St. Louis Children's Hospital, Washington University, St. Louis, Missouri.
Department of Pediatrics, UCSF Benioff Children's Hospital, Oakland, California.
Biol Blood Marrow Transplant. 2018 Jun;24(6):1216-1222. doi: 10.1016/j.bbmt.2018.01.023. Epub 2018 Jan 31.
Allogeneic hematopoietic stem cell transplantation (HSCT) can cure transfusion-dependent thalassemia (TDT). In a multicenter trial we investigated the efficacy of reduced-intensity conditioning (RIC) before unrelated donor (URD) HSCT in children with TDT. Thirty-three children, ages 1 to 17 years, received bone marrow (BM) or umbilical cord blood (UCB) allografts. Median time to neutrophil engraftment was 13 days (range, 10 to 25) and 24 days (range, 18 to 49) and platelet engraftment 23 days (range, 12 to 46) and 50 days (range, 31 to 234) after BM and UCB allografts, respectively. With a median follow-up of 58 months (range, 7 to 79), overall and thalassemia-free survival was 82% (95% CI, .64% to .92%) and 79% (95% CI, .6% to .9%), respectively. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) after BM and UCB allografts was 24% and 44%; the 2-year cumulative incidence of chronic extensive GVHD was 29% and 21%, respectively; 71% of BM and 91% of UCB recipients discontinued systemic immunosuppression by 2 years. Six patients who had Pesaro risk class 2 (n = 5) and class 3 (n = 1) died of GVHD (n = 3), viral pneumonitis (n = 2) and pulmonary hemorrhage (n = 1). Outcomes after this RIC compared favorably with URD HSCT outcomes for TDT and supported engraftment in 32 of 33 patients. Efforts to reduce GVHD and infectious complications are being pursued further.
异基因造血干细胞移植（HSCT）可治愈依赖输血的地中海贫血（TDT）。在一项多中心试验中，我们研究了在依赖输血的地中海贫血儿童中，采用非亲缘供体（URD）HSCT 前进行低强度预处理（RIC）的疗效。33 名 1 至 17 岁的儿童接受了骨髓（BM）或脐带血（UCB）异基因移植物。中性粒细胞植入的中位时间分别为 BM 移植物 13 天（范围 10 至 25）和 UCB 移植物 24 天（范围 18 至 49），血小板植入的中位时间分别为 BM 移植物 23 天（范围 12 至 46）和 UCB 移植物 50 天（范围 31 至 234）。中位随访时间为 58 个月（范围 7 至 79），总生存率和无地中海贫血生存率分别为 82%（95%CI，.64%至.92%）和 79%（95%CI，.6%至.9%）。BM 和 UCB 移植物后，Ⅱ至Ⅳ级急性移植物抗宿主病（GVHD）的累积发生率分别为 24%和 44%；2 年慢性广泛型 GVHD 的累积发生率分别为 29%和 21%；2 年时，71%的 BM 受者和 91%的 UCB 受者停用了全身免疫抑制剂。6 名患者中有 5 名患有佩萨罗风险类别 2（n=5）和 1 名患有类别 3（n=1），死于 GVHD（n=3）、病毒性肺炎（n=2）和肺出血（n=1）。这种 RIC 后的结果与 TDT 的 URD HSCT 结果相比是有利的，并且支持了 33 名患者中的 32 名的植入。正在进一步努力减少 GVHD 和感染并发症。
