单倍体造血干细胞移植联合后置大剂量环磷酰胺治疗儿童恶性血液病25例  

Human leukocyte antigen-haploidentical hematopoietic stem cell transplantation with high-dose, posttransplant cyclophosphamide for children with malignant hematopathy

作　　者：彭智勇[1] 吴学东[1] 冯晓勤[1] 何岳林[1] 裴夫喻 伊文芳[1] 石磊[1] 刘华颖[1] 李娜[1] 陈嘉琪[1] 李春富[1] 

机构地区：[1]510515广州,南方医科大学南方医院儿科

出　　处：《中华器官移植杂志》2014年第1期8-12,共5页Chinese Journal of Organ Transplantation

摘　　要：目的探讨单倍体造血干细胞移植联合后置大剂量环磷酰胺治疗儿童恶性血液病的临床疗效。方法回顾性分析2009年6月至2012年11月期间接受单倍体造血干细胞移植25例患儿的资料，患者中位年龄为9．0岁（1．2～13．0岁），男女比例为13：12。其中原发疾病分别为急性淋巴细胞白血病13例，急性粒细胞白血病7例，非霍奇金淋巴瘤2例，慢性粒细胞白血病2例，幼年慢性粒一单核细胞白血病1例。供者均为1级血缘亲属，供、受者HLA配型2个位点不合6例，〉2个位点不合19例。移植前预处理主要为环磷酰胺＋氟达拉滨＋白消安，部分患者加用达利珠单抗、阿糖胞苷、依托泊苷或司莫司汀及接受全身照射等。移植物抗宿主病（GVHD）的预防采用大剂量环磷酰胺（40或50mg·kg^-1·d^-1，用3～4d）＋他克莫司＋吗替麦考酚酯。结果中位随访时间为25个月。25例28d内供者细胞嵌合率均大于95％，60d后1例骨髓衰竭。粒细胞植活中位时间为22．5d（17～46d），血小板植活中位时间为20．5d（12~67d）。I～Ⅱ度急性GVHD、Ⅲ～Ⅳ度急性GVHD和慢性GVHD分别发生7例（28％）、1例（4％o）和3例（12％），另3例（12％）因复发给予供者淋巴细胞或外周血造血干细胞输注后发生Ⅲ～Ⅳ度急性GVHD。移植后3年总体存活率、无事件存活率、非复发死亡率及复发率分别为28％、28％、40％和32％。结论单倍体造血干细胞移植联合后置大剂量环磷酰胺治疗儿童恶性血液病能有效地预防GVHD，早期植入效果较好，但复发及移植后继发全血细胞减少的发生率高，治疗方案有待进一步改善。Objective To evaluated the efficacy of human leukocyte antigen （HLA）- haploidentical hematopoietic stem cell transplantation （HSCT） using high-dose post-transplant （HP） cyclophosphamide （Cy） as prophylaxis of graft versus host diseases （GVHD）. Method Twenty-five children with high-risk acute lymphoblastic leukemias （n = 13）, acute myeloid leukemia （n = 7）, chronic myeloid leukemia （n = 2）, lymphoma （n = 2） or childhood juvenile myelomonocytic leukemia （n = 1） received HSCT from ≥2 HLA mismatched relative donors from June 2009 to November 2012. All patients received conditioning regimen which was consisted of fludarabine, busulfan, Cy, thiotepa, with or without total body irradiation and HP Cy （40 or 50 mg/kg i. v. on day 3 and day 4 after transplantation）. Result The median follow-up time was 25 months. Donor chimerism was ≥95% on day 28 in all patients. The median time to neutrophils ≥0. 5 × 10^9/L and platelets ≥20 × 10^9/L was 22.5 and 20. 5 days, respectively. The cumulative incidence of grade I -H acute GVHD （aGVHD）, grade Ⅲ-IV aGVHD, and chronic GVHD was 28o/oo, 4% and 12%, respectively. Three patients developed garde Ⅲ-IV aGVHD after donor lymphocyte infusion for relapse. The cumulative incidence of relapse and non-relapse mortality were 32% and 40%, respectively. The cumulative overall survival and event-free survival at 3 years were 28% and 28%, respectively. Conclusion HLA-haploidentical HSCT with HP Cy for children with malignant hematological disorders is a viable option when lack of HLA matched sibling and unrelated donors. The rate of severe GVHD is acceptable. But posttransplant cytopenia and relapse still are major hinder, and the. protocol should be modified.

关 键 词：造血干细胞移植 环磷酰胺 白血病 移植物抗宿主病 

分 类 号：R733[医药卫生—肿瘤]