Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy
Por:
Halter, JP, Schupbach, WMM, Mandel, H, Casali, C, Orchard, K, Collin, M, Valcarcel, D, Rovelli, A, Filosto, M, Dotti, MT, Marotta, G, Pintos, G, Barba, P, Accarino, A, Ferra, C, Illa, I, Beguin, Y, Bakker, JA, Boelens, JJ, de Coo, IFM, Fay, K, Sue, CM, Nachbaur, D, Zoller, H, Sobreira, C, Simoes, BP, Hammans, SR, Savage, D, Marti, R, Chinnery, PF, Elhasid, R, Gratwohl, A, Hirano, M
Publicada:
1 oct 2015
Resumen:
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 510/10) 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.
Filiaciones:
Halter, JP:
Univ Basel Hosp, Haematol, CH-4031 Basel, Switzerland
Schupbach, WMM:
Univ Hosp Bern, Inselspital, Dept Neurol, Bern, Switzerland
Univ Bern, CH-3012 Bern, Switzerland
Univ Paris 06, Dept Neurol, Inst Cerveau & Moelle Epiniere, Ctr Invest Clin 9503, Paris, France
CHU Pitie Salpetriere, INSERM, Paris, France
Mandel, H:
Rambam Med Ctr Haifa, Haifa, Israel
Casali, C:
Univ Roma La Sapienza, Dep SBMC, Rome, Italy
Orchard, K:
Southampton Univ Hosp, Southampton, Hants, England
Collin, M:
Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
Valcarcel, D:
Univ Autonoma Barcelona, Univ Hosp Vall dHebron, E-08193 Barcelona, Spain
Rovelli, A:
Univ Milano Bicocca, San Gerardo Hosp, Dept Paediat, BMT Unit,MBBM Fdn, Monza, Italy
Filosto, M:
Univ Hosp Spedali Civili, Sect Neuromuscular Dis & Neuropathies, Neurol Clin, Brescia, Italy
Dotti, MT:
Univ Siena, Dept Neurol Neurosurg & Behav Sci, I-53100 Siena, Italy
Marotta, G:
Univ Hosp, Stem Cell Transplant & Cellular Therapy Unit, Siena, Italy
Pintos, G:
Univ Hosp Germans Trias & Pujol, Dept Paediat, Barcelona, Spain
Barba, P:
Univ Autonoma Barcelona, Univ Hosp Vall dHebron, E-08193 Barcelona, Spain
Accarino, A:
Univ Autonoma Barcelona, Univ Hosp Vall dHebron, E-08193 Barcelona, Spain
Ferra, C:
Univ Hosp Germans Trias & Pujol, Catalan Inst Oncol, Dept Haematol, Barcelona, Spain
Illa, I:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain
Beguin, Y:
CHU Sart Tilman Liege, Liege, Belgium
Bakker, JA:
Leiden Univ, Med Ctr, Dept Clin Chem & Lab Med, Leiden, Netherlands
Boelens, JJ:
Univ Med Ctr Utrecht, Paediat Blood & Marrow Transplantat Program, Utrecht, Netherlands
de Coo, IFM:
Erasmus MC, Univ Med Ctr Rotterdam, Dept Neurol & Child Neurol SKZ, Rotterdam, Netherlands
Fay, K:
Royal N Shore Hosp, Dept Haematol, Sydney, NSW, Australia
St Vincent Hosp, Sydney, NSW, Australia
Sue, CM:
Univ Sydney, Royal N Shore Hosp, Dept Neurol, Sydney, NSW 2006, Australia
Nachbaur, D:
Med Univ Innsbruck, Dept Med 2, A-6020 Innsbruck, Austria
Med Univ Innsbruck, Dept Med 5, A-6020 Innsbruck, Austria
Zoller, H:
Med Univ Innsbruck, Dept Med 2, A-6020 Innsbruck, Austria
Med Univ Innsbruck, Dept Med 5, A-6020 Innsbruck, Austria
Sobreira, C:
Univ Sao Paulo, Ribeirao Preto Sch Med, Div Neurol, Dept Neurosci, BR-05508 Sao Paulo, Brazil
Simoes, BP:
Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Internal Med, Stem Cell Transplantat Unit, BR-05508 Sao Paulo, Brazil
Hammans, SR:
Wessex Neurol Ctr Southampton, Southampton, Hants, England
Savage, D:
Columbia Univ, New York, NY 10027 USA
Marti, R:
Univ Autonoma Barcelona, Univ Hosp Vall dHebron, E-08193 Barcelona, Spain
ISCIII, Biomed Network Res Ctr Rare Dis CIBERER, Barcelona, Spain
Chinnery, PF:
Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
Elhasid, R:
Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dana Childrens Hosp, IL-69978 Tel Aviv, Israel
Gratwohl, A:
Univ Basel Hosp, Haematol, CH-4031 Basel, Switzerland
Hirano, M:
Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA
Green Published, Bronze
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