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.