Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy.

Abstract

Haematopoietic stem cell transplantation has been proposed as treatment for mitochondrial neurogastrointestinal encephalomyopathy, a rare fatal autosomal recessive disease due to TYMP mutations that result in thymidine phosphorylase deficiency. We conducted a retrospective analysis of all known patients suffering from mitochondrial neurogastrointestinal encephalomyopathy who underwent allogeneic haematopoietic stem cell transplantation between 2005 and 2011. Twenty-four patients, 11 males and 13 females, median age 25 years (range 10-41 years) treated with haematopoietic stem cell transplantation from related (n = 9) or unrelated donors (n = 15) in 15 institutions worldwide were analysed for outcome and its associated factors. Overall, 9 of 24 patients (37.5%) were alive at last follow-up with a median follow-up of these surviving patients of 1430 days. Deaths were attributed to transplant in nine (including two after a second transplant due to graft failure), and to mitochondrial neurogastrointestinal encephalomyopathy in six patients. Thymidine phosphorylase activity rose from undetectable to normal levels (median 697 nmol/h/mg protein, range 262-1285) in all survivors. Seven patients (29%) who were engrafted and living more than 2 years after transplantation, showed improvement of body mass index, gastrointestinal manifestations, and peripheral neuropathy. Univariate statistical analysis demonstrated that survival was associated with two defined pre-transplant characteristics: human leukocyte antigen match (10/10 versus <10/10) and disease characteristics (liver disease, history of gastrointestinal pseudo-obstruction or both). Allogeneic haematopoietic stem cell transplantation can restore thymidine phosphorylase enzyme function in patients with mitochondrial neurogastrointestinal encephalomyopathy and improve clinical manifestations of mitochondrial neurogastrointestinal encephalomyopathy in the long term. Allogeneic haematopoietic stem cell transplantation should be considered for selected patients with an optimal donor.

• Authors: Joerg P Halter, W Michael, M Schüpbach, Hanna Mandel, Carlo Casali, Kim Orchard, Matthew Collin, David Valcarcel, Attilio Rovelli, Massimiliano Filosto, Maria T Dotti, Giuseppe Marotta, Guillem Pintos, Pere Barba, Anna Accarino, Christelle Ferra, Isabel Illa, Yves Beguin, Jaap A Bakker, Jaap J Boelens, Irenaeus F M de Coo, Keith Fay, Carolyn M Sue, David Nachbaur, Heinz Zoller, Claudia Sobreira, Belinda Pinto Simoes, Simon R Hammans, David Savage, Ramon Martí, Patrick F Chinnery, Ronit Elhasid, Alois Gratwohl, Michio Hirano
• Journal: Brain : a journal of neurology (Brain) Vol. 138 Issue Pt 10 Pg. 2847-58 (Oct 2015) ISSN: 1460-2156 [Electronic] England
• PMID: 26264513 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Thymidine Phosphorylase

Topics

• Adolescent
• Adult
• Body Weight
• Brain (pathology)
• Child
• Female
• Follow-Up Studies
• Hematopoietic Stem Cell Transplantation (methods)
• Humans
• Intestinal Pseudo-Obstruction (surgery)
• Magnetic Resonance Imaging
• Male
• Mitochondrial Encephalomyopathies (surgery)
• Muscular Dystrophy, Oculopharyngeal
• Neural Conduction (physiology)
• Neurologic Examination
• Neutrophils
• Ophthalmoplegia (congenital)
• Retrospective Studies
• Survival Analysis
• Thymidine Phosphorylase (metabolism)
• Transplantation, Homologous (methods)
• Treatment Outcome
• Young Adult