14800-DvRappard

37 Metachromatic leukodystrophy: disease spectrum and approaches for treatment 2 Umbilical cord blood transplantation (UBCT) is an alternative for bone marrow transplantation with the advantage of quicker availability, less GvHD, lower risk of morbidity and mortality and better correction of enzymatic deficiency. 24 Furthermore, UCBT is associated with higher rates of full-donor chimerism compared to mixed chimerism in HSCT or sibling transplantation. 31 Martin et al 21 report a study of 27 children with both infantile and juvenile onset treated with UCBT. In asymptomatic patients at the time of transplantation, UCBT resulted in successful replacement of the missing enzyme and disease stabilization. In the group of children with moderate to severe symptoms (N= 19), 7 children died. The surviving children of the symptomatic group did not benefit fromUCBT. Cable et al 33 report a 5-year follow up of three affected siblings with juvenile MLD after an UCBT. The patient who was symptomatic at the time of the transplant deteriorated and now remains in a vegetative state . The other two patients, who were asymptomatic at the time of transplant stabilized within a year after UCBT and have remained stable regarding neurological examination, neuroimaging, nerve conduction studies and neuropsychological evaluations. Presymptomatic patients with the juvenile and adult formare good candidates for HSCT. Late-infantile patients often deteriorate, even if transplantation has been performed before the first symptoms. 22 In mildly symptomatic patients, the decision whether or not to performHSCT is difficult. Better knowledge of the natural history of MLD will help in predicting clinical course in individual patients. One approach is by Kehrer et al 34 who modified the Gross Motor Function Classification (GMFC) system for MLD, which can be used as a robust and easy to use classification system to evaluate gross motor function from 18 months onwards. Both late infantile as well as juvenile patients who have just lost the independency of unsupported walking have a probability of more than 60% to have no locomotion or sitting without support within one year. 34 This is an important criterion in the decision process of whether to perform a HSCT or not, since it takes around 6-18 months before the donor cells become functional. Although the first approach of using HSCT as a treatment for MLDwas published in 1985 (Bayever, Lancet 1985), we are still short of a systematic analysis of its effectiveness of HSCT. Such a study is further complicated by the different protocols that are being used for HSCT worldwide. Therefore, no standard decision criteria exist for the utilization of HSCT. To develop these, we need a systematic overview of the long-term effects and outcome of HSCT in a large sample of patients.