Madden Lisa M, Hayashi Robert J, Chan Ka Wah, Pulsipher Michael A, Douglas Dorothea, Hale Gregory A, Chaudhury Sonali, Haut Paul, Kasow Kimberly A, Gilman Andrew L, Murray Lisa M, Shenoy Shalini
Division of Pediatric Hematology Oncology, Washington University School of Medicine, St. Louis, Missouri.
Pediatric Blood & Marrow Stem Cell Transplant Program, Methodist Children's Hospital of South Texas, San Antonio, Texas.
Biol Blood Marrow Transplant. 2016 Aug;22(8):1467-1472. doi: 10.1016/j.bbmt.2016.04.025. Epub 2016 May 6.
Reduced-intensity conditioning (RIC) before hematopoietic stem cell transplantation (HCT) in children could result in fewer complications during follow-up compared with myeloablative regimens. Hence, many RIC regimens are under investigation, but long-term follow-up is essential. We describe late follow-up beyond 2 years post-HCT in 43 children with nonmalignant disorders who underwent related or unrelated donor (56%) HCT on a multicenter study using a RIC regimen (alemtuzumab, fludarabine, and melphalan) followed by bone marrow (n = 30), peripheral blood (n = 3), or umbilical cord blood (n = 10) HCT for immune dysfunction, bone marrow failure, metabolic disorders, or hemoglobinopathy. Recipients (median age, 7.5 years; range, 3 to 26) underwent HCT 2 to 8 years (median, 3.1 years) before this report. Full donor (67%) or stable mixed chimerism (33%) was noted without late graft rejection. Five patients (12%) required systemic immunosuppression therapy (IST) beyond 2 years post-HCT for graft-versus-host disease (GVHD); 2 patients died 38 and 79 months later, whereas the others improved, enabling an IST wean. Overall, 17 complications were documented in 10 patients (23%). Complications not related to GVHD included hypothyroidism (n = 2), low grade neoplasms (n = 2), and delayed puberty (n = 1). One patient with GVHD had ovarian failure; all other postpubertal females resumed normal ovarian function. Twenty-seven of 28 school-age recipients were functioning at grade level. RIC HCT recipients thus had few regimen-related toxicities during long-term follow-up. However, objective long-term follow-up is still necessary to identify complications so timely intervention may be planned.
与清髓性方案相比，儿童造血干细胞移植（HCT）前采用减低强度预处理（RIC）可使随访期间的并发症减少。因此，许多RIC方案正在研究中，但长期随访至关重要。我们描述了43例非恶性疾病儿童在接受HCT 2年以上的后期随访情况，这些儿童在一项多中心研究中接受了相关或无关供者（56%）的HCT，采用RIC方案（阿仑单抗、氟达拉滨和美法仑），随后进行骨髓（n = 30）、外周血（n = 3）或脐带血（n = 10）HCT，用于免疫功能障碍、骨髓衰竭、代谢紊乱或血红蛋白病。在本报告之前，受者（中位年龄7.5岁；范围3至26岁）在2至8年（中位3.1年）前接受了HCT。观察到完全供者嵌合（67%）或稳定混合嵌合（33%），无晚期移植物排斥。5例患者（12%）在HCT后2年以上因移植物抗宿主病（GVHD）需要全身免疫抑制治疗（IST）；2例患者分别在38个月和79个月后死亡，而其他患者病情改善，能够停用IST。总体而言，10例患者（23%）记录了17例并发症。与GVHD无关的并发症包括甲状腺功能减退（n = 2）、低度肿瘤（n = 2）和青春期延迟（n = 1）。1例GVHD患者出现卵巢功能衰竭；所有其他青春期后的女性恢复了正常卵巢功能。28例学龄受者中有27例学业成绩达标。因此，RIC HCT受者在长期随访期间与方案相关的毒性反应很少。然而，仍需要进行客观的长期随访以识别并发症，以便能够计划及时干预。
