Bauchat Andrea, Polishchuk Veronika, Fabrizio Vanessa A, Brondon Jennifer E, Page Kristin M, Driscoll Timothy A, Martin Paul L, Mahadeo Kris M, Kurtzberg Joanne, Prasad Vinod K
Division of Pediatric Transplant and Cellular Therapy, Duke University, 2400 Pratt Street, Box 102502, Durham, NC 27705, United States.
Division of Pediatric Hematology, Oncology, and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E Chicago Ave, Chicago, IL 60611, United States.
Stem Cells Transl Med. 2025 Jan 17;14(1). doi: 10.1093/stcltm/szae080.
Ceroid lipofuscinosis neuronal (CLN) encompasses rare inherited neurodegenerative disorders that present in childhood with clinical features including epilepsy, psychomotor delay, progressive vision loss, and premature death. Published experience utilizing umbilical cord blood transplant (UCBT) for these disorders is limited. This retrospective analysis includes patients with CLN (2, 3, and 5) who underwent UCBT from 2012 to 2020. All subjects (n = 8) received standard-of-care myeloablative conditioning. Four also enrolled in clinical trial NCT02254863 and received intrathecal DUOC-01 cells posttransplant. Median age at UCBT was 5.9 years. All subjects achieved neutrophil engraftment with >95% donor chimerism at a median of 28.5 days. Sinusoidal obstructive syndrome was not observed. Severe acute graft-versus-host disease occurred in 12.5%. Other complications included autoimmune hemolytic anemia (25%) and viral reactivation/infection (62.5%). No transplant-related mortality was observed. Two CLN2 patients died, 1 from progressive disease and 1 from unknown cause at days +362 and +937, respectively. With median follow-up of 8 years, overall survival at 100 days and 24 months was 100% and 88%, respectively. Three of 4 CLN3 subjects stabilized Hamburg motor and language scores. While UCBT appears safe and feasible in these patients, given the variable expression and natural history, extended follow-up and further studies are needed to elucidate the potential impact of UCBT on clinical outcomes.
神经元蜡样脂褐质沉积症（CLN）是一类罕见的遗传性神经退行性疾病，于儿童期发病，临床特征包括癫痫、精神运动发育迟缓、进行性视力丧失和过早死亡。关于利用脐带血移植（UCBT）治疗这些疾病的已发表经验有限。这项回顾性分析纳入了2012年至2020年期间接受UCBT的CLN（2型、3型和5型）患者。所有受试者（n = 8）均接受了标准的清髓性预处理。其中4名患者还参与了临床试验NCT02254863，并在移植后接受了鞘内注射DUOC-01细胞。UCBT时的中位年龄为5.9岁。所有受试者均实现了中性粒细胞植入，中位植入时间为28.5天，供体嵌合率>95%。未观察到肝窦阻塞综合征。严重急性移植物抗宿主病的发生率为12.5%。其他并发症包括自身免疫性溶血性贫血（25%）和病毒再激活/感染（62.5%）。未观察到与移植相关的死亡。两名CLN2型患者分别在+362天和+937天死亡，1例死于疾病进展，1例死因不明。中位随访8年，100天和24个月时的总生存率分别为100%和88%。4名CLN3型受试者中有3名的汉堡运动和语言评分保持稳定。虽然UCBT在这些患者中似乎是安全可行的，但鉴于其表现的变异性和自然病程，需要延长随访时间并开展进一步研究，以阐明UCBT对临床结局的潜在影响。
