非血缘相关脐血移植治疗儿童高危白血病的临床观察

Unrelated umbilical cord blood transplantation as a treatment for children with malignant leukemia

目的非血缘脐血具有快速寻求、容易得到和HLA配型不严格的特点，该文进行了非血缘相关脐血移植（UD-UCBT）治疗儿童恶性白血病的研究并探讨其疗效问题。方法对6例难治性白血病患儿，包括3例急性淋巴细胞白血病（2例高危CR1，1例标危CR2），2例幼年慢性粒单细胞白血病（1例缓解期，1例加速期）和1例急性髓系白血病（AML—M5，CR1）进行了非血缘相关脐血移植，HLA高分辨1例全相合，1例5个位点相合，1例4个位点相合，3例3个位点相合。预处理选用白消安／环磷酰胺／ATG或全身放疗／环磷酰胺／ATG为主方案。于0d回输脐血，有核细胞中位数为8．51×10^7／kg，CD34^＋细胞中位数为1．81×10^5／kg。预防移植物抗宿主病（GVHD）采用环孢霉素A、甲基泼尼松龙和骁悉或CD25单抗。结果中性粒细胞绝对值（ANC）≥0．5×10^9／L和PLT≥20×10^9／L的中位天数分别是＋13d、＋30d，移植证据均为供者型。4例出现Ⅰ-Ⅲ度GVHD，均控制。随访中位时间12个月，未发生慢性GVHD，现存活4例血型均转为供者型，无复发。结论脐血提供快速有效的造血干细胞，为治疗儿童白血病提供良好时机，非血缘相关脐血移植能耐受HLA多个位点不相合。急性GVHD发生率也较高，存在移植物抗白血病作用。

Objective Unrelated umbilical cord blood has the clear benefits of rapid availability and a reduced stringency of requirement for HLA match. The aim of this study was to investigate the efficacy of unrelated umbilical cord blood transplantation （UCBT） in the treatment of malignant leukemia in children. Methods Six children with malignant leukemia, including three cases of acute lymphocyte leukemia [ two high-risk patients and one standard-risk patient in complete remission （CR）], two juvenile myelomonocytic leukemia （one in CR and one in the accelerating stage）, and one acute myeloblastic leukaemia （in CR） , received a UCBT. The umbilical cord blood grafts were HLA-matched （n = 1 ） or HLA-mismatched at 1 （ n = 1 ） or 2 （ n = 1 ） or 3 （ n = 3 ） loci. Busulfan/cyclopbosphamide/antithymocyte globulin （ATG） or total body irradiation （TBI）/cyclopbosphamide/ATG was involved in the myeloablative pretreatment regimen. The median infused donor nucleated cell was 8.51 × 10^7/kg of recipient weight, and the CD34^＋ cell was 1.81× 10^5/kg of recipient weight. Cyclosporin, corticoid, mycophenolate mofetil and daclizumab were used for prophylaxis of acute graft versus host disease （GVHD）. Results The time to reach an absolute neutrophil count of 0.5 ×10^9/L ranged from 11 to 35 days （median： 13 days） and the time to reach a platelet count of 20 × 10^9/L ranged from 27 to 68 days （median： 30 days） after transplantation, and the donors＇ hematopoietic stem cells were shown in these patients. Four patients developed grade Ⅰ to Ⅲ acute GVHD but responded to steroids and daclizumab. Chronic GVHD was not found during a 3-16-month follow-up. Four patients survived and did not relapse during the follow-up. Conclusions Unrelated umbilical cord blood is an alternative source of hematopoietic stem cells for patients with leukemia. UCBT can tolerate 1-2 HLA mismatches. The incidence of acute GVHD is high in UCBT recipients.