14800-DvRappard

164 Chapter 10 with our results they report efficacy for early, pre-symptomatic transplantation in later onset MLD types, but their results also show benefit from HCT for long-term survival across all MLD subtypes. Gröschel et al report a TRM of 17% in a group of juvenile MLD patients. They recommend HCT in juvenile patients with an age of onset older than 4 years, pre- or early symptomatic (GMFC-MLD 0 or 1 and IQ ≥ 85), MRI score less than 17 (with a temporal or parietooccipital white matter subscore ≤4) and no involvement of U-fibers. The difference in TRM between the studies of Boucher and Gröschel and our own study without TRM is remarkable. Boucher et al already point out the influence of older, less advanced protocols. In line with this, different conditioning regimens used are likely of influence on TRM. Another difference is that our cohort consisted of a large percentage (46%) of adult patients, whilst the other studies did not include adult patients or a smaller number of patients. How the subtype would influence TRM however is not evident, since the same conditioning regimens are used for children and adults. Moreover, the incidence of GvHD tends to be lower in children than in adults. 6 Due to the slower disease progression, adults are usually less affected at time of transplantation, which might make them less vulnerable to the intensive treatment. Unfortunately, some of our patients did deteriorate cognitively after HCT, despite a pre- or early symptomatic clinical condition prior to HCT. The disease manifestations in these patients are not only evidently slower compared to the natural course, but also progress despite stable white matter changes on MRI. This suggests neuroaxonal involvement less amenable to HCT. Why this decline is seen in some, but not all patients after HCT remains unclear. Both late-infantile, juvenile and adult patients were affected, so the subtype and pace of disease progression are not the only explanation. Longer follow- up time also for adult patients in whom the disease evolves slower will clarify how the disease fully unfolds after HCT and how often this cognitive deterioration occurs. Pre- and early symptomatic juvenile and adult MLD patients are good candidates for HCT. In these patients, HCT can result in disease stabilization or even some improvement. Patients that are no longer able to walk without support and whose cognitive function is clearly affected (IQ below 75) will have no benefit from HCT. However, for patients with early juvenile onset IQ should preferably be higher, whereas in adult patients the slow disease progression may allow less stringent criteria. Additionally, brain abnormalities (rated with the MLD-Loes score) are predictive for outcome: patients with an MRI score above 15 at diagnosis are likely to have an unsuccessful outcome. Quantitative MRS can further be of aid in determining eligibility for HCT in ambiguous cases: severely reduced concentrations of (NAA) indicate low probability of a successful outcome.