14800-DvRappard

82 Chapter 5 In summary, the unique characteristics of this study are the comparison of disease evolution in transplanted patients with the natural course of patients no longer eligible for HCT diagnosed within the same period. We used consistent decision guidelines, and all transplantations were performed in a single center. Our data show that, under these conditions, HCT is a safe procedure for pre- and early symptomatic MLD patients with the juvenile or adult type, resulting in disease stabilization and high disease burden- free survival, with even the suggestion of some brain repair, reflected by improvement of brain MRI abnormalities, confirming earlier findings. 6,16-19 For late-infantile and more advanced patients, results are not encouraging, suggesting that HCT in those at best delays disease progression. Our study shows that motor and cognitive functions are good predictors of outcome. Clearly, affected motor (inability to walk without support) and cognitive (IQ below 75) function resulted in no benefit of HCT. Brain MRI abnormalities were more severe and extensive in the patients rejected for HCT than in successfully transplanted patients, suggesting that an MRI score above 15 is associated with an unsuccessful outcome. As HCT remains an intensive treatment and initial neurological worsening is to be expected, it should not be considered if the disease has progressed beyond a certain stage. In these patients, HCT negatively impacts their life and that of their families at a time, which should be cherished before the inevitable frank disease progression sets in. Limitations of our study are its retrospective character and the inevitable selection bias resulting from the fact that nontransplanted patients were more severely affected than the transplanted patients at diagnosis. In addition, some issues remain: 3 patients (2 with the juvenile form) showed cognitive deterioration, despite presymptomatic HCT, and despite relatively stable white matter changes, suggesting neuronal involvement perhaps less amenable to treatment with HCT. Peripheral nerve involvement seemed unaltered, despite normal circulating enzyme levels after transplantation. Lastly, especially for the slowly progressive adult forms, follow-up needs to be longer to fully evaluate effects of HCT. As the best moment for HCT is as early as possible and before clinical disease onset, it is of utmost importance to test all siblings of an index case, including older ones. For more advanced and late-infantile patients, results are discouraging. For the majority of patients evaluated, HCT was no longer an option neither did they qualify for treatment trials, emphasizing the need of earlier diagnosis and better treatment strategies.