Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease
Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease
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DOI：
10.1056/nejmoa042604
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发表时间：
2005-05-19
影响因子：
158.5
通讯作者：
Kurtzberg, J
中科院分区：
文献类型：
--
作者：
Escolar, ML;Poe, MD;Kurtzberg, J
背景：婴儿克拉伯病在儿童早期会导致进行性神经功能恶化和死亡。我们假设，在症状出现之前移植无关供体的脐带血，将有利于改变因家族史而被诊断为该病的新生儿的自然病史。我们比较了这些新生儿之间的结果与婴儿谁接受移植后的发展，症状和未治疗的受影响的children.METHODS队列的结果：11无症状的新生儿（年龄范围，12至44天）和14有症状的婴儿（年龄范围，142至352天）与婴儿克拉布氏病进行移植的脐带血从无关的捐助者清髓性化疗后。植入，生存，和神经发育功能进行了纵向评估为4个月至6 years.Results：供体细胞植入和生存率分别为100%和100%，分别为无症状的新生儿（中位随访，3.0年）和100%和43%，分别为有症状的婴儿（中位随访，3.4年）。存活的患者表现出供体来源的造血细胞的持久植入，并恢复正常的血液半乳糖苷酶水平。在出现症状之前接受移植的婴儿表现出进行性中枢髓鞘形成和发育技能的持续获得，大多数具有与年龄相适应的认知功能和接受性语言技能，但少数有轻度至中度的表达性语言延迟和轻度至重度的粗大运动功能延迟。症状发作后接受移植的儿童有最小的神经系统improvement.CONCLUSIONS：婴儿克拉布氏病的新生儿无关供体的脐带血移植有利地改变了疾病的自然史。在婴儿出现症状后进行移植并没有导致实质性的神经功能改善。
BACKGROUND:Infantile Krabbe's disease produces progressive neurologic deterioration and death in early childhood. We hypothesized that transplantation of umbilical-cord blood from unrelated donors before the development of symptoms would favorably alter the natural history of the disease among newborns in whom the disease was diagnosed because of a family history. We compared the outcomes among these newborns with the outcomes among infants who underwent transplantation after the development of symptoms and with the outcomes in an untreated cohort of affected children.METHODS:Eleven asymptomatic newborns (age range, 12 to 44 days) and 14 symptomatic infants (age range, 142 to 352 days) with infantile Krabbe's disease underwent transplantation of umbilical-cord blood from unrelated donors after myeloablative chemotherapy. Engraftment, survival, and neurodevelopmental function were evaluated longitudinally for four months to six years.RESULTS:The rates of donor-cell engraftment and survival were 100 percent and 100 percent, respectively, among the asymptomatic newborns (median follow-up, 3.0 years) and 100 percent and 43 percent, respectively, among the symptomatic infants (median follow-up, 3.4 years). Surviving patients showed durable engraftment of donor-derived hematopoietic cells with restoration of normal blood galactocerebrosidase levels. Infants who underwent transplantation before the development of symptoms showed progressive central myelination and continued gains in developmental skills, and most had age-appropriate cognitive function and receptive language skills, but a few had mild-to-moderate delays in expressive language and mild-to-severe delays in gross motor function. Children who underwent transplantation after the onset of symptoms had minimal neurologic improvement.CONCLUSIONS:Transplantation of umbilical-cord blood from unrelated donors in newborns with infantile Krabbe's disease favorably altered the natural history of the disease. Transplantation in babies after symptoms had developed did not result in substantive neurologic improvement.