探讨亲缘性单倍体造血干细胞联合无关脐血移植治疗儿童血液疾病的可行性

发布时间：2018-05-05 09:09

  本文选题：亲缘性单倍体供体 + 脐血　； 参考：《苏州大学》2014年硕士论文

【摘要】：异基因造血干细胞移植是根治儿童恶性血液病的主要方法。近年来随着移植技术的进步，亲缘性单倍体作为重要的干细胞来源得到了广泛的推广运用。本研究关注的是提高亲缘性单倍体移植疗效的临床措施，对亲缘性单倍体造血干细胞联合无关脐血移植这一技术在治疗儿童恶性血液疾病方面进行可行性探讨。 目的：评估应用亲缘性单倍体造血干细胞联合无关脐血移植治疗儿童恶性血液疾病的疗效和安全性。 方法： 1，病例资料：对2012年8月到12月间6例恶性血液病儿童进行了亲缘性单倍体造血干细胞联合无关脐血的移植。包括2例急性淋巴细胞性白血病（ALL），2例急性髓细胞性白血病（AML），1例慢性粒细胞性白血病（CML）和1例重型再生障碍性贫血（SAA）。中位年龄10岁，中位体重38.3Kg。对供体使用粒细胞刺激因子（G-CSF）进行动员，取骨髓和外周血干细胞作为移植源，未进行体外去除T细胞处理（TCD）。骨髓内中位单个核细胞（MNC）数7.00（1.51~12.13）×108/Kg，中位CD34+细胞数1.81（1.23~2.45）×106/Kg，外周血中位单个核细胞数7.96（4.09~14.64）×108/Kg，中位CD34+细胞数5.85（2.74~14.20）×106/Kg。在骨髓干细胞输注前4小时注射脐带血，1天后输注外周血干细胞。对受体应用个体化的清髓性预处理，预处理方案为改良马利兰/环磷酰胺（BU/CY）或环磷酰胺/全身照射（CY/TBI）。移植后，每日计数血细胞，监测造血重建。所有的受体均接受环胞霉素A、抗胸腺细胞球蛋白、霉酚酸酯和甲氨蝶呤（CsA+ATG+MMF+MTX）的强化联合免疫抑制，预防移植物抗宿主病（GVHD）。积极防治移植后其他并发症。对患者进行长期随访。 2，移植前检测：检测供体的人类白细胞抗原（HLA）-I、II类抗体、主要组织相容性Ⅰ类相关基因A（MICA）抗体、供受者的杀伤细胞免疫球蛋白样受体（KIR）基因型，进行移植前处理，提高移植成功率。 3、移植后检测：检测受者的短串联重复序列（STR），确定嵌合情况，预测复发风险。 4、移植后并发症防治：检测巨细胞病毒CMV-PP65抗原、CMV-DNA、人乳头瘤病毒（BKV）情况，早期预防，早期诊断，早期治疗，减少移植后并发症，降低严重程度。 结果： 1、1例患者存在HLA-I、II类抗体阳性，，移植前给予利妥昔单抗处理；所有患者MICA抗体均为阴性；2例患者存在KIR不相合，1例受体包含供体型。 2、移植后6例患者全部获得供体型植入。中性粒细胞植入中位时间为11.8（10~15）天，血小板植入中位时间为14.2（12~16）天。监测STR≥95%作为完全植入，其中位时间为18（14~21）天。 3、2例患者发生aGVHD，无重度aGVHD（III~IV度），无cGVHD发生。2例患者发生出血性膀胱炎（HC），其中1例存在多瘤病毒（BKV）感染。5例患者有巨细胞病毒（CMV）感染，其中3例病毒感染反复。1例患者并发侵袭性真菌感染（IFI）。无肝静脉闭塞综合症（VOD）发生。 4、中位随访时间为376.5天（136~496），5例患者无病生存，仅1例重型再生障碍性贫血病人在移植后136天死于间质性肺炎。 结论：亲缘性单倍体供体骨髓及外周血干细胞联合脐带血移植可致移植物快速植入、低GVHD发生率和高无病生存率。
[Abstract]:The transplantation of allogeneic hematopoietic stem cells is the main method for the treatment of malignant hematopathy in children . In recent years , with the advancement of transplantation technology , the genetic haploid is widely used as an important source of stem cell . This study is concerned with the clinical measures to improve the curative effect of genetic haploid transplantation .

Objective : To evaluate the efficacy and safety of the application of the combined unrelated umbilical cord blood transplantation in the treatment of malignant hematologic diseases in children .

Method :

1 . Case data : The transplantation of peripheral blood stem cells with unrelated cord blood was carried out in 6 children with malignant hematopathy between August and December 2012 . The median age was 10 years , median body weight was 38.3Kg . Peripheral blood stem cells were harvested 4 hours before the infusion of bone marrow stem cells . The number of mononuclear cells in the bone marrow was 7.96 ( 4.09 ~ 14.64 ) 脳 108 / Kg . The number of mononuclear cells in the bone marrow was 7.96 ( 4.09 ~ 14.64 ) 脳 108 / Kg . The number of mononuclear cells in the bone marrow was 7.96 ( 4.09 ~ 14.64 ) 脳 108 / Kg . The number of mononuclear cells in the bone marrow was 7.96 ( 4.09 ~ 14.64 ) 脳 108 / Kg . The graft versus host disease ( GVHD ) was prevented . All the recipients were followed up for long - term follow - up .

2 . Pre - transplantation detection : HLA - I and II antibodies of human leukocyte antigen ( HLA ) - I and II of donor were detected , and the main tissue - compatible class I - related gene A ( MICA ) antibody was detected , the genotype of killer cell immunoglobulin - like receptor ( KIR ) of the donor was genotyped , and the success rate of transplantation was improved .

3 . Detection after transplantation : Short tandem repeat sequence ( STR ) of the recipient is detected , the chimeric condition is determined , and the risk of recurrence is predicted .

4 . Prevention of complications after transplantation : Detection of cytomegalovirus CMV - PP65 antigen , CMV - DNA , human papillomavirus ( BKV ) , early prevention , early diagnosis , early treatment , reduced post - transplantation complications , and decreased severity .

Results :

1 . HLA - I and II antibodies were positive in 1 patient and rituximab was administered before transplantation .
All patients with MICA were negative ;
Two patients had a KIR mismatch and one receptor included donor type .

2 . All 6 patients received donor - type implantation . The median time of neutrophil implantation was 11.8 ( 10 - 15 ) days . The median time of platelet implantation was 14.2 ( 12 - 16 ) days . The monitoring STR 鈮

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