Methods
A 2-year-old Russian boy, first child of non-consanguineous parentage, presented to us with global developmental delay. Child had a history of prolonged seizures at 1½ years of age and was symptomatically managed in his native country. Subsequently child had total 5 episodes of right sided focal seizures. On examination, he had hypotonia, unable to stand or walk, no speech and had developmental delay (developmental age was 10 months at 2-years of age) with no evidence of dysmorphism or neurocutaneous markers. Magnetic resonance imaging (MRI) of brain revealed symmetrical and widespread abnormality of the white matter of the cerebrum, brainstem, and cerebellum.  Computerised tomography scan of head showed agenesis of corpus callosum & cerebellar vermis along with moderate ventriculomegaly. Genetic testing showed PLP-1 gene duplication confirming diagnosis of PMD. He then underwent an UCBT from a 10/10 matched unrelated cord at our centre. Parents gave written informed consent before transplant. Myeloablative conditioning was used with Busulfan day-9 to -6 (3.2mg/kg/day), Cyclophosphamide day-5 to -2 (50mg/kg/day), Rabbit anti-thymoglublin day-3 to -1 (2.5mg/kg/day) and Rituximab on day-8 (100mg/m2). Cord blood stem cell (CD34+) dose was 0.2 million/kg. Mycophenolate mofetil (MMF) and Cyclosporine were used as graft-vs-host disease (GVHD) prophylaxis.
Results
His neutrophil engrafted on day+29 and platelets on day+33. Post-transplant on day+30 he had reactivation of Cytomegalovirus and BK virus along with haemorrhagic cystitis which was managed successfully. On day+53, he had an episode of hematemesis and melena with sudden drop in hemoglobin. Upper and lower gastrointestinal endoscopies were performed. Biopsies were suggestive of MMF induced enterocolitis which resolved after discontinuation of MMF. Chimerism on day+32, day+56 and day+100, 1-year and 2-years was fully donor. There was no evidence of acute or chronic GVHD. His further post-transplant period was uneventful. Neurodevelopmental assessment was done at 12 months and 24 months post-transplant which showed overall improvement in all domain of development. His motor skills improved, he can walk independently, run with infrequent falls and climb stairs. Child could speak in sentences play with blocks and follow instructions and had better social communications skills. No further seizures were recorded post-transplant. At present child is more than two years post-transplant and has developmental age of 3 years at 4 years of age. MRI of brain 24-months post UCBT has shown no change in myelination.