Outcomes of Umbilical Cord Blood Transplantation in Children with Batten Disease

Introduction Neuronal ceroid lipofuscinoses (NCL, Batten Disease) are a class of lysosomal storage diseases caused by mutations in ceroid lipofuscinoses (CLN) genes. Neurological deterioration is influenced by the CLN subtype, but death typically occurs in childhood. Symptoms include visual impairment, behavioral changes, loss of motor and/or cognitive skills, and seizures. Umbilical cord blood transplant (UCBT) is effective in treating many lysosomal storage disorders but there is very limited experience in BD. Methods We retrospectively studied 6 patients (pt) with BD receiving UCBT between the ages of 4 months and 8.6 years at our center. All received myeloablative conditioning with busulfan, cyclophosphamide and ATG. Cyclosporine and mycophenolate were given for prophylaxis of GVHD. Pts 5 and 6 were concomitantly enrolled on clinical trial (NCT02254863) and also received intra-thecal injection of DUOC-01 cells after hematologic engraftment. Selected patient and donor characteristics are shown in Table 1: Results Patients received UCB grafts matching at 4/6-6/6 loci with a median pre-cryo cell dose of 7.2 (range, 5.1-35.1) x10 7 cells/kg. All pts engrafted neutrophil and platelets in a median of 25 (range, 12-34) and 39 days (range, 32-105), respectively. Four patients developed Grade 2-4 acute GvHD and 2 developed extensive chronic GvHD. Pt 1, the only patient transplanted after severe neurologic decline with advanced disease, died from progressive BD and aseptic shock 12 months post-UCBT. All others are alive at a median of 3.8 years (range, 0.5-5.5). Pt 2 has normal motor function, is nonverbal and was diagnosed with autism 2 years post UCBT. Her brain MRI is normal to date. Pt 3 is blind, has had occasional seizures, requires educational support and has no MRI evidence of BD. Pts 4 and 5 have age appropriate neurocognition, no seizures, and receive only visual support in school. Both have normal MRIs. It is too early to assess neurologic outcomes in Pt 6 (7 months post-UCBT). Conclusion UCBT is feasible in children with BD. At a median follow up of 3.8 years (range, 0.5-5.5), 5/6 patients are alive and 4/5 are neuro-cognitively stable and one developed new onset seizures post-transplant. All 5 surviving pts have no MRI evidence of disease. With the inherent variability of the different forms of BD, additional pts and continued follow-up is needed to fully understand the effect of UCBT on the natural history of BD.