单倍体骨髓移植治疗儿童难治复发性白血病  

Haploidentical bone marrow transplantation for treatment of refractory and relapsed childhood leukemia

作　　者：陈惠仁[1] 纪树荃[1] 王恒湘[1] 贾烨辉[1] 刘静[1] 阎洪敏[1] 薛梅[1] 朱玲[1] 潘世平[1] 肖名华[1] 

机构地区：[1]解放军空军总医院血液病研究中心,北京100036

出　　处：《中华儿科杂志》2001年第10期588-591,共4页Chinese Journal of Pediatrics

摘　　要：目的　探讨供者应用粒细胞集落刺激因子 (G CSF)和受者联合应用多种免疫抑制剂单倍体骨髓移植治疗儿童难治复发性白血病的可行性。方法　 8例难治复发性儿童白血病患儿中 ,高危急性非淋巴白血病 1例 ,急性淋巴白血病第 2次完全缓解 (CR2 )及以上的病例 6例 ,慢性粒细胞白血病加速期 1例 ,在清髓性预处理后接受单倍体供者的骨髓。供者应用G CSF 2 5 0 μg,连用 7d后采髓 ,受者移植物抗宿主病 (GVHD)的预防除环孢菌素A(CSA)和氨甲蝶呤 (MTX)外 ,在 - 4至 - 1d(移植前为“ -”)应用抗胸腺细胞球蛋白 (ATG) 5mg/ (kg·d) ,+7d(移植后为“ +”)开始加服霉酚酸酯(MMF)。结果　 8例患儿均植入成功 ,中性粒细胞大于 0 5× 10 9/L和血小板大于 2 0× 10 9/L的中位天数分别是 18d(范围 16～ 2 1d)和 19 5d(范围 17～ 2 7d)。急性Ⅱ°～Ⅳ°GVHD发生 4例 (5 0 % ) ,其中 2例急性Ⅱ度肠道GVHD ,2例急性Ⅲ度肠道GVHD ,可评价的 5例患儿均发生慢性GVHD ,无一例发生广泛性慢性GVHD。中位随访时间是 5 10d(范围 390～ 72 0d) ,死亡 3例 ,其中死于急性GVHD 2例 ,死于感染 1例。无病存活 5例。结论　单倍体骨髓移植治疗儿童难治复发性白血病是一种有效和安全方法 。Objective Allogeneic bone marrow transplantation (Allo BMT) is the most effective treatment for children with relapsed or high risk leukemia However, most patients who could benefit from Allo BMT lack an HLA identical sibling donor Using haploidentical donor for Allo BMT involves crossing HLA mismatched immunology barriers The purpose of this study was to explore the feasibility of haploidentical bone marrow transplantation in which the donors received granulocyte colony stimulating factor (G CSF) prior to harvest and sequential immunomodulation added to recipient for treatment of refractory and relapsed childhood leukemia. Methods Eight patients with refractory and relapsed leukemia received a non T cell depleted Allo BMT from HLA 2 3 antigen mismatched family donors One of them suffered from acute non lymphocytic leukemia (ANLL) which was classified as a high risk, 6 suffered from acute non lymphocytic leukemia (ALL) (at CR2 or >CR2), and 1 suffered from chronic myeloid leukemia (CML) at an accelerated phase All patients were treated with a myeloablative conditioning regimen consisting of high dose cytosine arabinoside (Ara C ), cyclophosphamide (CY) and total body irradiation (TBI) Donors received G CSF (Lenograstim, Chugai Pharmaceutical ) 250 μg/d for seven days before marrow harvest A four agent graft versus host disease (GVHD) prophylaxis program consisting of cyclosporin A (CSA), methotrexate (MTX), antithymocyte globulin (ATG, Fresenius) and mycophenolate mofetial (MMF, Hoffmann Roche) had been used ATG was infused at a dose of 5 mg per kilogram daily over an eight hour period The patients received MMF orally at a dose of 1.0 g daily from day 7 to day 100. Results All patients established successful engraftment The karyotyping of chromosome and HLA analysis confirmed that they were 100% donor derived The median time when granulocyte exceeded 0 5×10 9/L and platelet exceeded 20×10 9/L was 18 days (range 16 21 days) and 19 5 days (range 17

关 键 词：粒细胞集落刺激因子 单倍性骨髓移植 白血病 儿童 

分 类 号：R733.7[医药卫生—肿瘤]