Intramedullary spinal cord high-grade gliomas are rare and almost always fatal pediatric tumors. The current treatment paradigms are surgery, and radiotherapy. This is the first description of a toddler with an intramedullary cervical high-grade glioma harboring an anaplastic lymphoma kinase (ALK) fusion (KIF5B) whose treatment with the ALK inhibitor, alectinib, achieved clinical and radiological evidence of complete remission after six months of treatment. Our findings suggest that ALK inhibitors may emerge as an effective therapy in malignant spinal tumors with a dismal prognosis.

Background: Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) is a progressive autosomal recessive disorder characterized by cachexia, gastrointestinal (GI) dysmotility, ptosis, peripheral neuropathy and brain MRI white matter changes. Bi-allelic TYMP mutations lead to deficient thymidine phosphorylase (TP) activity, toxic accumulation of plasma nucleosides (thymidine and deoxyuridine), nucleotide pool imbalances and mtDNA instability. Death is mainly due to GI complications: intestinal perforation, peritonitis, and/or liver failure. Based on our previous observations in 3 patients with MNGIE, that platelet infusions resulted in a transient 40% reduction of plasma nucleoside levels, in 2005 we performed the first HSCT worldwide as a life-long source of TP in a patient with MNGIE. Procedure: HSCT was performed in a total of six patients with MNGIE. The multiple factors involved in the prognosis of this cohort were analyzed and compared to the literature experience. Results: Cell source was bone marrow in five patients and peripheral stem cells in one, all from fully HLA-matched related donors, including four who were TYMP mutation carriers. Four of six (66%) survived compared to the 37% survival rate in the literature. Reduced intensity conditioning regimen contributed to secondary graft failure in 2 patients. 15 years post-HSCT the first transplanted patient is seemingly cured. Severe GI symptoms pre-transplantation were mostly irreversible and a poor prognostic factor. Conclusions: Allogenic HSCT could constitute a curative therapeutic option for carefully selected, young, pre-symptomatic or mildly affected patients. Timing, donor selection and optimal conditioning protocol are major determinants of outcome. HSCT is inadvisable in patients with advanced MNGIE disease.