父母供者外周血单倍体移植治疗儿童难治性重型再生障碍性贫血

摘要

BACKGROUND:For pediatric patients with aplastic anemia in China, it is difficult to find human leucocyte antigen-matched sibling donors that are mostly replaced by parental donors. OBJECTIVE:To retrospectively analyze the clinical efficacy and safety of parental haploidentical peripheral blood hematopoietic stem cel transplantation in children with relapsed and refractory severe aplastic anemia. METHODS:Seventeen children with relapsed and refractory severe aplastic anemia who had no matched sibling or unrelated donor and failed to respond to immunosuppressive therapy were subjected to parental haploidentical peripheral blood hematopoietic stem cel transplantation. A conditioning regimen of fludarabine+cyclophosphamide+rabbit anti-human thymocyte immunoglobulin antibody and the triple therapy of methotrexate, cyclosporine A and mycophenolate mofetil were applied to prevent graft-versus-host disease. RESULTS AND CONCLUSION: (1) Of the 17 children, 16 cases (94%) reached hematopoietic reconstitution, and the median time of neutrophils≥ 0.5×109/L and platelets≥ 20×109/L was 13 (11-15) days and 17 (12-28) days, respectively. (2) Incidence of acute graft-versus-host disease was 47% (8 of 17 cases), including 29% (5/17) of grades I-II and 18% (3/17) of grades III-IV. Incidence of chronic graft-versus-host disease was 41% (7/17). (3) With a median folow-up duration of 268 (43-753) days, the overal survival rate was 70.6% (12/17). Five dead cases (29%) belonged to transplantation-related death, including one case of fungal skin infections, one case of graft-versus-host disease, three cases of severe lung infection. No relapse case was reported. These findings indicate that if there are no matched sibling or unrelated donors and the immunosuppression effect is poor, parental haploidentical peripheral blood hematopoietic stem cel transplantation is a safe and effective salvage treatment for children with relapsed and refractory severe aplastic anemia.%移植物抗宿主病：graft-versus-host disease，GVHD；人类白细胞抗原：humon leukocyte antigen，HLA 　　背景：在中国，儿童患者获得人类白细胞抗原相合同胞供者较困难，而以父母供者较多。　　目的：回顾性分析父母供者外周血单倍体造血干细胞移植治疗儿童复发难治性重型再生障碍性贫血的疗效及安全性。　　方法：纳入17例无人类白细胞抗原相合同胞及相合非血缘供者，且免疫抑制疗效不佳的复发难治性儿童重型再生障碍性贫血患者，行父母供者外周血单倍体造血干细胞移植。采用“氟达拉滨+环磷酰胺＋兔抗人胸腺细胞球蛋白抗体”预处理方案，应用环孢素+吗替麦考酚酯+甲氨蝶呤三联短程预防移植物抗宿主病。　　结果与结论：①患者17例中16例(94%)获得造血重建，中性粒细胞≥0.5×109 L-1和血小板≥20×109 L-1的中位时间分别为13(11-15) d和17(12-28) d。②急性移植物抗宿主病发生率47%(8/17)，其中Ⅰ-Ⅱ度29%(5/17)，Ⅲ-Ⅳ度18%(3/17)。慢性移植物抗宿主病发生率41%(7/17)。③中位随访268(43-753) d，12例存活，总生存率为71%(12/17)，死亡5例(29%)，均为移植相关死亡，其中1例植入失败死于皮肤真菌感染，1例死于移植物抗宿主病，3例死于肺部重症感染。无患儿移植后复发。④结果显示，无人类白细胞抗原相合同胞及相合非血缘供者，且免疫抑制疗效不佳的复发难治性儿童重型再生障碍性贫血患者，父母供者外周血单倍体造血干细胞移植是一种安全有效的挽救治疗方法。