无关血缘脐血移植治疗儿童恶性和非恶性疾病的临床研究

A clinical study of unrelated umbilical cord blood transplantation in pediatric patients with malignant and nonmalignant diseases

目的探讨无关血缘脐血移植治疗儿童恶性和非恶性疾病的临床疗效。方法24例进行非血缘脐血移植的患儿,包括急性淋巴细胞白血病(ALL)8例,急性髓系白血病(AML)4例,幼年慢性粒单细胞白血病(JMML)3例,慢性粒细胞白血病(CML)2例,骨髓增生异常综合征(MDS-RA)2例,急性混合型白血病、石骨症、X连锁肾上腺脑白质营养不良、Ⅵ型黏多糖和慢性肉芽肿各1例。HLA高分辨全相合6例,5个位点相合10例,4个位点相合5例,3个位点相合3例。预处理选用白消安(Bu)/环磷酰胺(CTX)/抗胸腺球蛋白(ATG)或全身放疗(TBI)/CTX/ATG为主方案。6例ALL采用TBI/CTX/ATG,其中2例加鬼臼乙叉苷(VP16),18例采用Bu/CTX/ATG,其中3例JMML加马法兰,1例ALL和1例AML加VP16,3例非恶性疾病加塞替哌。于0d回输脐血有核细胞中位数为5.26(2.26～13.3)×107/kg,CD34细胞中位数为2.86(0.79～9.8)×105/kg。预防急性移植物抗宿主病(aGVHD)采用环孢素A和甲基泼尼松龙(MP)或骁悉,出现Ⅲ～Ⅳ度aGVHD者,加用CD25单抗。结果脐血干细胞粒系植入率为91.7%(22/24),1例ALL未植入,1例CML于+130d排斥;血小板植入率为83.3%(20/24),中性粒细胞≥0.5×109/L中位天数+15(+13～+28)d;血小板≥20×109/L中位天数+38(+25～+100)d。7例出现Ⅰ～Ⅱ度aGVHD;1例出现Ⅲ度aGVHD,给予MP均控制;2例出现Ⅳ度aGVHD,给予MP及CD25单抗后未控制。随访中位时间28(9～96)个月,均未发生慢性GVHD(cGVHD)。现存活14例血型均转为供者型;死亡10例,其中原发病复发2例(急变期CML和婴儿型ALL各1例),Ⅳ度aGVHD合并感染2例,6例感染(CMV间质性肺炎4例,霉菌性肺炎2例)。结论无关血缘脐血是快速的造血干细胞来源之一,为恶性疾病患儿争取了治疗时间;因其cGVHD发生率低,对非恶性疾病患儿的治疗更具优势。

Objective To evaluate the efficacy of unrelated umbilical cord blood transplantation in the treatment of malignant and nonmalignant diseases in children. Methods Twenty-four children, including 20 with malignant diseases （8 acute lymphocyte leukaemia, four acute myeloid leukaemia, 3 juvenile myelomonoeytic leukemia, 2 chronic myeloid leukemia, 2 myelodysplastic syndrome （RA） , 1 acute mixed leukemia） and 4 with nonmalignant disease （ 1 osteopetrosis, 1 X-linked adrenoleukodystrophy, 1 mucopolysaccharidosis, 1 chronic granulomatous disease） , were received unrelated umbilical cord blood transplantation （UCBT） and analyzed. UCB gratis were HLA-matched （n = 6） or HLA-mismatched at 1 （n = 10） or 2 （n = 5） or 3 （n = 3） loci. The pretreatment regimen was busulfan/ cyclophosphamide/Antithymocyte globulin （ATG） or total body irradiation （TBI） /cyclophosphamide/ATG. The median dose of donor nucleated cell counts was 5.26 ×10^7/kg of recipient body weight, and CD34＋ cell counts was 2.86 ×10^5 / kg of recipient body weight. The prophylaxis of acute graft versus host disease （GVHD） is cyclosporin, eortieoid or MMF. Results The engraftment rate of granulocytes and platelets is 92% and 83.3%, respectively. The time when granulocytes exceed 0.5 ×10^9/L and platelets exceed 20 ×10^9/L was day 15 and day 38 after transplantation, respectively. One ALL case failed in primary graft. Seven patients experienced grade Ⅰ to Ⅱacute GVHD, one patient experienced grade ⅢaGVHD and responded to steroids and daclizumab. Two patients experienced grade ⅣaGVHD and did not respond to steroids and daclizumab. No chronic GVHD were found during the 28 month follow-up. Fourteen patients survived and ten died （ 2 from relapse, 2 from combined ⅣaGVHD and infection, 4 from CMV interstitial pneumonia , 2 from fungal pneumonia）. Conclusions The unrelated umbilical cord blood hematopoietic stem cells are an alternative source of hematopoietic stem cells for patients with malignant and nonmalignant disease.