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CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2016; 74(12): 953-966
DOI: 10.1590/0004-282X20160155
ARTICLE

Neurological outcomes after hematopoietic stem cell transplantation for cerebral X-linked adrenoleukodystrophy, late onset metachromatic leukodystrophy and Hurler syndrome

Desfechos neurológicos após transplante de células tronco hematopoiéticas na adrenoleucodistrofia ligada ao X, forma cerebral, na leucodistrofia metacromática de início tardio e na síndrome de Hurler
Jonas Alex Morales Saute
1   Hospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Porto Alegre RS, Brasil;
2   Hospital de Clínicas de Porto Alegre, Laboratório de Identificação Genética, Porto Alegre RS, Brasil;
5   Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Ciências Médicas, Porto Alegre RS, Brasil;
,
Carolina Fischinger Moura de Souza
1   Hospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Porto Alegre RS, Brasil;
,
Fabiano de Oliveira Poswar
7   Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Genética e Biologia Molecular; Porto Alegre RS, Brasil;
,
Karina Carvalho Donis
1   Hospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Porto Alegre RS, Brasil;
3   Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Saúde da Criança e do Adolescente, Porto Alegre RS, Brasil;
,
Lillian Gonçalves Campos
4   Hospital de Clínicas de Porto Alegre, Serviço de Radiologia, Porto Alegre RS, Brasil;
5   Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Ciências Médicas, Porto Alegre RS, Brasil;
,
Adriana Vanessa Santini Deyl
6   Hospital de Clínicas de Porto Alegre, Serviço de Oncologia Pediátrica, Porto Alegre, Brasil;
,
Maira Graeff Burin
1   Hospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Porto Alegre RS, Brasil;
,
Carmen Regla Vargas
1   Hospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Porto Alegre RS, Brasil;
13   Universidade Federal do Rio Grande do Sul, Faculdade de Farmacia, Porto Alegre, Brasil
,
Ursula da Silveira Matte
7   Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Genética e Biologia Molecular; Porto Alegre RS, Brasil;
8   Hospital de Clínicas de Porto Alegre, Laboratório de Terapia Gênica, Porto Alegre RS, Brasil;
9   Universidade Federal do Rio Grande do Sul, Departamento de Genética e Biologia Molecular, Porto Alegre RS, Brasil;
,
Roberto Giugliani
1   Hospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Porto Alegre RS, Brasil;
3   Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Saúde da Criança e do Adolescente, Porto Alegre RS, Brasil;
5   Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Ciências Médicas, Porto Alegre RS, Brasil;
7   Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Genética e Biologia Molecular; Porto Alegre RS, Brasil;
8   Hospital de Clínicas de Porto Alegre, Laboratório de Terapia Gênica, Porto Alegre RS, Brasil;
9   Universidade Federal do Rio Grande do Sul, Departamento de Genética e Biologia Molecular, Porto Alegre RS, Brasil;
,
Maria Luiza Saraiva-Pereira
1   Hospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Porto Alegre RS, Brasil;
2   Hospital de Clínicas de Porto Alegre, Laboratório de Identificação Genética, Porto Alegre RS, Brasil;
7   Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Genética e Biologia Molecular; Porto Alegre RS, Brasil;
10   Universidade Federal do Rio Grande do Sul, Departamento de Bioquímica, Porto Alegre RS, Brasil;
,
Leonardo Modesti Vedolin
4   Hospital de Clínicas de Porto Alegre, Serviço de Radiologia, Porto Alegre RS, Brasil;
5   Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Ciências Médicas, Porto Alegre RS, Brasil;
,
Lauro José Gregianin
6   Hospital de Clínicas de Porto Alegre, Serviço de Oncologia Pediátrica, Porto Alegre, Brasil;
12   Universidade Federal do Rio Grande do Sul, Departamento de Pediatria, Porto Alegre RS, Brasil;
,
Laura Bannach Jardim
1   Hospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Porto Alegre RS, Brasil;
2   Hospital de Clínicas de Porto Alegre, Laboratório de Identificação Genética, Porto Alegre RS, Brasil;
3   Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Saúde da Criança e do Adolescente, Porto Alegre RS, Brasil;
5   Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Ciências Médicas, Porto Alegre RS, Brasil;
7   Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Genética e Biologia Molecular; Porto Alegre RS, Brasil;
11   Universidade Federal do Rio Grande do Sul, Departamento de Medicina Interna, Porto Alegre RS, Brasil;
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ABSTRACT

Hematopoietic stem cell transplantation (HSCT) is the only available treatment for the neurological involvement of disorders such as late-onset metachromatic leukodystrophy (MLD), mucopolysaccharidosis type I-Hurler (MPS-IH), and X-linked cerebral adrenoleukodystrophy (CALD).

Objective To describe survival and neurological outcomes after HSCT for these disorders.

Methods Seven CALD, 2 MLD and 2 MPS-IH patients underwent HSCT between 2007 and 2014. Neurological examinations, magnetic resonance imaging, molecular and biochemical studies were obtained at baseline and repeated when appropriated.

Results Favorable outcomes were obtained with 4/5 related and 3/6 unrelated donors. Two patients died from procedure-related complications. Nine transplanted patients were alive after a median of 3.7 years: neurological stabilization was obtained in 5/6 CALD, 1/2 MLD, and one MPS-IH patient. Brain lesions of the MPS-IH patient were reduced four years after HSCT.

Conclusion Good outcomes were obtained when HSCT was performed before adulthood, early in the clinical course, and/or from a related donor.

RESUMO

O transplante de células tronco hematopoiéticas (TCTH) é o único tratamento disponível para o envolvimento neurológico de doenças como a leucodistrofia metacromática (MLD), a mucopolissacaridose tipo I-Hurler (MPS-IH) e a adrenoleucodistrofia (CALD).

Objetivos Descrever a sobrevida e os desfechos neurológicos após o TCTH nessas doenças.

Métodos Sete pacientes CALD, 2 MLD e 2 MPS-IH realizaram TCTH entre 2007 e 2014. Avaliações neurológicas, ressonância nuclear magnética e estudos bioquímicos e moleculares foram feitos no baseline e repetidos quando apropriado.

Resultados Desfechos favoráveis foram obtidos em 4/5 TCTH de doadores relacionados e em 3/6 não relacionados. Dois pacientes faleceram de complicações do procedimento. Nove transplantados sobreviveram após uma mediana de 3,7 anos: estabilização neurológica foi obtida em 5/6 CALD, ½ MLD e em um caso MPS-IH. As lesões encefálicas de um caso MPS-IH reduziram-se quatro anos após o TCTH.

Conclusão Bons desfechos foram obtidos quando o TCTH foi feito antes da vida adulta, cedo no curso clínico e/ou a partir de um doador relacionado.

hematopoietic stem cell transplantation - leukodystrophy, metachromatic - mucopolysaccharidosis I - adrenoleukodystrophy
transplante de células-tronco hematopoiéticas - leucodistrofia metacromática - mucopolissacaridose I - adrenoleucodistrofia

Support:

C.F.M. de Souza received travel grants and speaker honoraria from Genzyme, which has products for MPS-I treatment. R. Giugliani is an investigator in clinical trials sponsored by Genzyme and Shire, and has received travel grants and speaker honoraria from these companies, which have products for MPS-I and MLD treatment, respectively.


C.R.Vargas, U.S. Matte, R. Giugliani, M.L. Saraiva-Pereira and L.B. Jardim received research fellowships from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil.


SUPPLEMENTAL MATERIAL



Publication History

Received: 17 June 2016

Accepted: 24 August 2016

Article published online:
06 September 2023

© 2023. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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