Kato Shunichi
Department of Cell Transplantation Regenerative Medicine, Tokai University School of Medicine, 143 Kamikasuya, Isehara, Kanagawa, Japan.
Brain Nerve. 2007 Apr;59(4):339-46.
X-linked adrenoluekodystrophy (X-ALD) is a clinically heterogenous disorder ranging from the rapidly progressive childhood cerebral form to the milder adrenomyeloneuropathy in adults, and some persons with ALD protein (ALDP) defects may remain asymptomatic for life. Hematopoietic cell transplantation (HCT) is currently the only effective therapy for cerebral X-ALD. Stem cell sources for transplantation are bone marrow, peripheral blood and cord blood. The donor should be HLA identical with the recipient and can be found within family members or from unrelated bone marrow or cord blood donor pools. Preparative conditioning with supralethal chemoradiotherapy is needed for donor cell engraftment, and immunosuppressive agents are given for months as prophylaxis against graft-verus-host disease (GVHD). Worldwide data collection reported 56% of long term survival. Neurologic and MRI severity at the time of transplantation was the most important factor for survival and the degree of improvement after transplantation. More than 90% of early stage patients have survived with good quality of life for a long term, whereas patients with advanced disease had the higher mortality rate during transplant procedures and the neurological abnormalities progressed in most of them. Patients with a parietal-occipital lobe pattern of demyelination demonstrated a greater mean loss of performance IQ (PIQ) points than patients with a frontal lobe pattern of demyelination. Thus, boys with early-stage disease benefit from HCT, whereas boys with advanced disease may be candidates for experimental therapies.
X连锁肾上腺脑白质营养不良(X-ALD)是一种临床异质性疾病,范围从儿童期快速进展的脑型到成人期较轻的肾上腺脊髓神经病,一些患有ALD蛋白(ALDP)缺陷的人可能终生无症状。造血细胞移植(HCT)是目前治疗脑型X-ALD的唯一有效疗法。移植的干细胞来源是骨髓、外周血和脐带血。供体应与受体HLA相同,可在家庭成员中找到,或来自无关的骨髓或脐带血供体库。为使供体细胞植入,需要进行超致死剂量的放化疗预处理,并给予免疫抑制剂数月以预防移植物抗宿主病(GVHD)。全球数据收集报告长期生存率为56%。移植时的神经功能和MRI严重程度是生存及移植后改善程度的最重要因素。超过90%的早期患者长期存活且生活质量良好,而晚期疾病患者在移植过程中的死亡率较高,且大多数患者的神经异常会进展。与额叶脱髓鞘模式的患者相比,顶枕叶脱髓鞘模式的患者表现出更大的平均操作智商(PIQ)得分损失。因此,早期疾病的男孩从HCT中获益,而晚期疾病的男孩可能是实验性治疗的候选者。