Allogeneic hematopoietic stem cell transplantation for the treatment of X-linked adrenoleukodystrophy

doi:10.3969/j.issn.2095-4344.2013.10.025

Abstract

Abstract:

BACKGROUND: X-linked adrenoleukodystrophy is the hot research in the field of genetics at home and abroad and there still lacks of the effective treatment method.
OBJECTIVE: To analyze the efficacy and complications of allogeneic hematopoietic stem cell transplantation on the treatment of X-linked adrenoleukodystrophy in two cases.
METHODS: Two cases of X-linked adrenoleukodystrophy treated with allogeneic hematopoietic stem cell transplantation were selected from Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology for comprehensive analysis and genetic testing. The success of the transplantation and the occurrence of complications after transplantation were observed.
RESULTS AND CONCLUSION: Both of the two cases were childhood cerebral X-linked adrenoleukodystrophy. One case had successful allogeneic hematopoietic stem cell transplantation but with serious transplant-related complications, and the other one case was failed. Allogeneic hematopoietic stem cell transplantation is an effective method for treatment of early childhood cerebral X-linked adrenoleukodystrophy, but the ultimate effect was related with the success of transplantation and post-transplant complications and other factors, and the efficacy of allogeneic hematopoietic stem cell transplantation still needs long-term investigation.

Key words: stem cells, stem cell academic discussion, stem cell transplantation, X-linked adrenoleukodystrophy, hematopoietic stem cell transplantation, allogeneic, fatty acids, peroxisome, genetics, pathogenesis, diagnosis, treatment, transplant-related complications, fungal infections

CLC Number:

R318

Zhang Jing, Ying Yan-qin, Luo Xiao-ping, Zhang Yi-cheng, Xiao Yi. Allogeneic hematopoietic stem cell transplantation for the treatment of X-linked adrenoleukodystrophy[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(10): 1868-1867.

Figures/Tables 7

治疗过程：患者自确诊后，口服罗伦佐油予以治疗。与其父人类白细胞抗原5/6相合，行氟达拉滨移植后白舒非移植后抗人胸腺细胞球蛋白预处理：氟达拉滨30 mg /(m2·d)×5 d，白舒非3.2 mg/(kg·d)×3 d，抗人胸腺细胞球蛋白20 mg/(kg·d)×4 d。在移植前12 d即开始使用吗替麦考酚酯，移植前5 d开始使用环孢素A。于2011-01-31及2011-02-01行外周血干细胞移植，输注过程顺利。白细胞于移植后10 d植活，血小板计数于移植后11 d植活，移植后肢体肌力降低，认知能力未加重。预后评估：①移植中反复出现巨细胞病毒DNA，考虑为巨细胞病毒血症，行抗病毒治疗。②移植后40 d出现大便次数增多，隐血阳性。考虑为不洁饮食所致，但也不能排除肠道移植物抗宿主病的可能。③加强了抗生素及环孢素A用量，并口服激素布地奈德加强肠道对激素的吸收，控制了肠道反应。④移植后64 d出现伪膜性肠炎。⑤移植后66 d出现出血性膀胱炎，给予改善微循环、止血、补液、碱化尿液、雌激素减少盆腔血流、加强抗感染等。⑥移植后118 d出现心力衰竭，给予强心、利尿、改善心肌缺血等处理后，并加用甲泼尼龙控制症状。⑦出现肢体瘫痪，给予营养神经等治疗，渐停用环孢素A。⑧移植后163 d出现肠道移植物抗宿主病，加用他克莫司。⑨移植后180 d出现神经系统症状(双眼向上凝视、呼吸无应答、偶尔出现抽搐等)，给予镇静、降低颅内压、抗惊厥、改善脑缺血、促进大脑功能恢复等处理。⑩移植后202 d出现肺部感染加重并呼吸困难，不能配合呼吸机，气管插管后行呼吸机辅助通气，最后家属签字放弃治疗出院。 1.2 病例2 临床资料：患者男，17岁。因“确诊肾上腺脑白质营养不良7年，右下肢活动障碍半月”于2010-10-28入院。2003年10月在华中科技大学同济医学院附属同济医院确诊为“肾上腺脑白质营养不良”，皮肤及牙龈黏膜偏黑，无明显智力发育障碍。欲行脐带血干细胞移植，但脐带血量不足，行外周血干细胞采集以备用。患儿哥哥2003年诊断为“肾上腺脑白质营养不良”，于2004年7月去世。治疗：患儿确诊后，口服罗伦佐油。行氟达拉滨+白舒+抗人胸腺细胞球蛋白预处理。先后给予连续5 d氟达拉滨30 mg/(m2·d)，连续两天白舒非3.2 mg/(kg·d)，连续4 d抗人胸腺细胞球蛋白20 mg/(kg·d)。移植前 12 d即开始使用吗替麦考酚酯，移植前9天开始使用环孢素A，2010-12-05行脐血干细胞移植，移植后行促进干细胞植入、防治移植后并发症的对症支持处理。移植后出现双下肢无力，活动障碍。预后：①移植后43 d查血常规未移植成活。②短串联重复序列聚合酶链反应法分析，移植前后血样的短串联重复序列基因型没有改变。③2011-01-31取血样STR基因座型别检测未显示干细胞移植成活的迹象。④给予输注自体造血干细胞后血象逐渐恢复。⑤病程中出现咳嗽，胸部CT示肺部感染，给予抗感染治疗。"

4 异基因造血干细胞移植治疗X-连锁肾上腺脑白质营养不良的已发表文献分析资料来源：检索有关异基因造血干细胞移植治疗X-连锁肾上腺脑白质营养不良的文献[31-32]，检索时间范围在1990至2012年，以“X-连锁肾上腺脑白质营养不良(x-linked adrenoleukodystrophy)；造血干细胞移植(hematopoietic stem cell transplantation)；异基因(allogeneic)；脂肪酸类(Fatty acids)；过氧化酶体(peroxisome)；发病机理(pathogenesis)；遗传学(genetics)；移植相关并发症(transplant-related complications)”为检索词，选取文献29篇[34-62]。纳入标准：①异基因造血干细胞移植治疗X-连锁肾上腺脑白质营养不良的病例分析。②异基因造血干细胞移植治疗X-连锁肾上腺脑白质营养不良的相关文献。排除标准：①重复研究、普通综述或Meta分析类文章。②排除较陈旧的理论观点。分析指标：①异基因造血干细胞移植治疗X-连锁肾上腺脑白质营养不良的机制。②异基因造血干细胞移植治疗X-连锁肾上腺脑白质营养不良的病例分析。③异基因造血干细胞移植治疗X-连锁肾上腺脑白质营养不良的相关文献分析。④异基因造血干细胞移植治疗X-连锁肾上腺脑白质营养不良的问题。 X-连锁肾上腺脑白质营养不良的发病机制文献分析：X-连锁肾上腺脑白质营养不良特征性的生化异常时饱和非分支极长链脂肪酸特别是二十六烷酸异常积聚，极长链脂肪酸全部在亚细胞结构过氧化物酶体内经β-氧化进行代谢，极长链脂肪酸在分解代谢前须活化形成极长链脂肪酸-乙酰辅酶A，该反应有极长链脂肪酸-乙酰辅酶A催化，X-连锁肾上腺脑白质营养不良患者体内过氧化物酶体合成极长链脂肪酸-乙酰辅酶A的反应明显减少，因此曾有人假设极长链脂肪酸在体内异常积聚是由基因突变所致[33]。对X-连锁肾上腺脑白质营养不良的发病机制研究的相关文献分析，见表2。"

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