Course and management of allogeneic stem cell transplantation in patients with mitochondrial neurogastrointestinal encephalomyopathy
Course and management of allogeneic stem cell transplantation in patients with mitochondrial neurogastrointestinal encephalomyopathy
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DOI：
10.1007/s00415-012-6572-9
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发表时间：
2012-12-01
影响因子：
6
通讯作者：
Rovelli, Attilio
中科院分区：
文献类型：
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作者：
Filosto, Massimiliano;Scarpelli, Mauro;Rovelli, Attilio
线粒体神经胃肠脑肌病（MNGIE）是一种常染色体隐性遗传疾病，由编码胸苷磷酸化酶（TP）的基因突变引起。异基因造血干细胞移植（HSCT）已被提议作为MNGIE患者的治疗方法，最近已开发出一种在这种情况下进行HSCT的标准化方法。我们报告的移植过程中，管理和短期随访的两个MNGIE患者接受HSCT。干细胞的来源是从第一个患者的HLA 9/10等位基因匹配的无关供体和第二个患者的HLA 10/10等位基因匹配的同胞供体中提取的骨髓。两例患者均获得完全供体嵌合体，我们观察到两例患者血沉棕黄层TP活性恢复，尿核苷浓度降低。移植后的临床随访显示胃肠道动力障碍、腹部绞痛和腹泻得到改善。神经功能评估保持不变。然而，第1例患者在HSCT后15个月死于胃肠道梗阻和休克;第2例患者在术后8个月死于感染性休克后的呼吸窘迫。虽然HSCT纠正了生化异常并改善了胃肠道症状，但对于已经处于不良医疗状况的受试者来说，该程序可能具有风险，因为许多MNGIE患者都是如此。由于移植相关的发病率和死亡率随着疾病的进展和合并症的数量而增加，MNGIE患者应在相对健康时接受HSCT，以尽量减少手术并发症。无论如何，许多受影响的患者对疾病的自然史仍然不完全了解，并且尚不清楚何时是进行移植的最佳时间。HSCT治疗潜力的进一步线索可能来自对更多非移植和移植患者的长期观察，这将使我们能够回答MNGIE患者是否、如何以及何时需要HSCT治疗的问题。
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder caused by mutations in the gene encoding thymidine phosphorylase (TP). Allogeneic hematopoietic stem cell transplantation (HSCT) has been proposed as a treatment for patients with MNGIE and a standardized approach to HSCT in this condition has recently been developed. We report on the transplant course, management and short-term follow-up in two MNGIE patients who underwent HSCT. The source of stem cells was bone marrow taken from an HLA 9/10 allele-matched unrelated donor in the first patient and from an HLA 10/10 allele-matched sibling donor in the second. Both patients achieved full donor chimerism, and we observed restoration of buffy coat TP activity and lowered urine nucleoside concentrations in both of them. The post-transplant clinical follow-up showed improvement in gastrointestinal dysmotility, abdominal cramps and diarrhea. Neurological assessment remained unchanged. However, the first patient died 15 months after HSCT due to gastrointestinal obstruction and shock; the second patient died 8 months after the procedure due to respiratory distress following septic shock. Although HSCT corrects biochemical abnormalities and improves gastrointestinal symptoms, the procedure can be risky in subjects already in poor medical condition as are many MNGIE patients. Since transplant-related morbidity and mortality increases with progression of the disease and number of comorbidities, MNGIE patients should be submitted to HSCT when they are still relatively healthy, in order to minimize the complications of the procedure. Anyway, there is still incomplete knowledge on the natural history of the disease in many affected patients and it is not yet clear when the best time to do a transplant is. Further clues to the therapeutic potential of HSCT could result from a prolonged observation in a greater number of non-transplanted and transplanted patients, which would allow us to answer the questions of if, how and when MNGIE patients require HSCT treatment.