Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy

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; G. Barros Navarro; J. F. Benoist; J. Bierau; A. Bucalossi; M. A. Carluccio; J. Coll-Canti; M. S. Cotelli; T. Diesch; R. Di Fabio; M. A. Donati; J. H. Garvin; K. Hill; L. Kappeler; T. Ku Hne; M. C. Lara; M. Lenoci; G. Lucchini; W. Marques; H. P. Mattle; A. Meyer; R. Parini; J. R. Passweg; F. Pieroni; A. Rodriguez-Palmero; F. Santus; M. Scarpelli; P. Schlesser; F. Sicurelli; M. Stern; A. B. Stracieri; P. Tonin; J. Torres-Torronteras; J. C. Voltarelli; I. Zaidman

doi:10.1093/brain/awv226

Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy

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. BoelensIrenaeus 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, G. Barros Navarro, J. F. Benoist, J. Bierau, A. Bucalossi, M. A. Carluccio, J. Coll-Canti, M. S. Cotelli, T. Diesch, R. Di Fabio, M. A. Donati, J. H. Garvin, K. Hill, L. Kappeler, T. Ku Hne, M. C. Lara, M. Lenoci, G. Lucchini, W. Marques, H. P. Mattle, A. Meyer, R. Parini, J. R. Passweg, F. Pieroni, A. Rodriguez-Palmero, F. Santus, M. Scarpelli, P. Schlesser, F. Sicurelli, M. Stern, A. B. Stracieri, P. Tonin, J. Torres-Torronteras, J. C. Voltarelli, I. Zaidman

Centro San Giovanni di Dio - Fatebenefratelli

Research output: Contribution to journal › Article › peer-review

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

Original language	English
Pages (from-to)	2847-2858
Number of pages	12
Journal	Brain
Volume	138
Issue number	10
DOIs	https://doi.org/10.1093/brain/awv226
Publication status	Published - Oct 1 2015

Keywords

allogeneic haematopoietic stem cell transplantation
mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)
outcome
risk factors
thymidine phosphorylase

ASJC Scopus subject areas

Clinical Neurology
Medicine(all)

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10.1093/brain/awv226

Cite this

Halter, J. P., Michael, W., Schüpbach, M., Mandel, H., Casali, C., Orchard, K., Collin, M., Valcarcel, D., Rovelli, A., Filosto, M., Dotti, M. T., Marotta, G., Pintos, G., Barba, P., Accarino, A., Ferra, C., Illa, I., Beguin, Y., Bakker, J. A., ... Zaidman, I. (2015). Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy. Brain, 138(10), 2847-2858. https://doi.org/10.1093/brain/awv226

Halter, JP, Michael, W, Schüpbach, M, 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, Pinto Simoes, B, Hammans, SR, Savage, D, Martí, R, Chinnery, PF, Elhasid, R, Gratwohl, A, Hirano, M, Barros Navarro, G, Benoist, JF, Bierau, J, Bucalossi, A, Carluccio, MA, Coll-Canti, J, Cotelli, MS, Diesch, T, Di Fabio, R, Donati, MA, Garvin, JH, Hill, K, Kappeler, L, Ku Hne, T, Lara, MC, Lenoci, M, Lucchini, G, Marques, W, Mattle, HP, Meyer, A, Parini, R, Passweg, JR, Pieroni, F, Rodriguez-Palmero, A, Santus, F, Scarpelli, M, Schlesser, P, Sicurelli, F, Stern, M, Stracieri, AB, Tonin, P, Torres-Torronteras, J, Voltarelli, JC & Zaidman, I 2015, 'Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy', Brain, vol. 138, no. 10, pp. 2847-2858. https://doi.org/10.1093/brain/awv226

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title = "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 ",

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doi = "10.1093/brain/awv226",

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AU - Halter, Joerg P.

AU - Michael, W.

AU - Schüpbach, M.

AU - Mandel, Hanna

AU - Casali, Carlo

AU - Orchard, Kim

AU - Collin, Matthew

AU - Valcarcel, David

AU - Rovelli, Attilio

AU - Filosto, Massimiliano

AU - Dotti, Maria T.

AU - Marotta, Giuseppe

AU - Pintos, Guillem

AU - Barba, Pere

AU - Accarino, Anna

AU - Ferra, Christelle

AU - Illa, Isabel

AU - Beguin, Yves

AU - Bakker, Jaap A.

AU - Boelens, Jaap J.

AU - De Coo, Irenaeus F M

AU - Fay, Keith

AU - Sue, Carolyn M.

AU - Nachbaur, David

AU - Zoller, Heinz

AU - Sobreira, Claudia

AU - Pinto Simoes, Belinda

AU - Hammans, Simon R.

AU - Savage, David

AU - Martí, Ramon

AU - Chinnery, Patrick F.

AU - Elhasid, Ronit

AU - Gratwohl, Alois

AU - Hirano, Michio

AU - Barros Navarro, G.

AU - Benoist, J. F.

AU - Bierau, J.

AU - Bucalossi, A.

AU - Carluccio, M. A.

AU - Coll-Canti, J.

AU - Cotelli, M. S.

AU - Diesch, T.

AU - Di Fabio, R.

AU - Donati, M. A.

AU - Garvin, J. H.

AU - Hill, K.

AU - Kappeler, L.

AU - Ku Hne, T.

AU - Lara, M. C.

AU - Lenoci, M.

AU - Lucchini, G.

AU - Marques, W.

AU - Mattle, H. P.

AU - Meyer, A.

AU - Parini, R.

AU - Passweg, J. R.

AU - Pieroni, F.

AU - Rodriguez-Palmero, A.

AU - Santus, F.

AU - Scarpelli, M.

AU - Schlesser, P.

AU - Sicurelli, F.

AU - Stern, M.

AU - Stracieri, A. B.

AU - Tonin, P.

AU - Torres-Torronteras, J.

AU - Voltarelli, J. C.

AU - Zaidman, I.

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N2 - 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

AB - 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

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KW - mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)

KW - outcome

KW - risk factors

KW - thymidine phosphorylase

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Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy

Abstract

Keywords

ASJC Scopus subject areas

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