Adult metachromatic leukodystrophy treated by allo-SCT and a review of the literature

Abstract

Five patients with adult-onset metachromatic leukodystrophy (MLD) underwent allo-SCT. Conditioning was reduced in intensity and grafts were obtained from voluntary unrelated donors. All but one graft were depleted of T-lymphocytes. Patient age at transplantation varied from 18 to 29 (median, 27) years. Two patients rejected their graft and MLD progressed. The recipient of the unmanipulated graft converted to complete donor chimerism with normalization of arylsulphatase A (ARSA) levels. Despite ARSA normalization, he deteriorated. Another patient was a mixed chimera. Following escalated doses of donor lymphocyte infusions he converted to complete donor chimerism. His levels of ARSA correlated positively with the percentage of donor cells and MLD was not progressive. The fifth patient died after 35 days from complications associated with GVHD. We conclude that results of allo-SCT in symptomatic MLD patients are poor. However, allo-SCT may stop progression of MLD in selected patients.

Hematopoietic SCT: a useful treatment for late metachromatic leukodystrophy

“…Our patients had a more rapid progression of MLD during the transplantation period, an observation also reported by de Hosson et al 11 Deterioration of the parameters investigated slowed and ultimately stopped, then remaining stable for as long as 18 years after transplantation (as in patient A). The time between the transplantation and the arrest of progression was individual, but it was within 12-24 months, an observation that concurs with other published material.…”

“…20 Generally, patients with MLD tend to have higher scores for Verbal IQ than for performance IQ. 9,11,12 The same reference values for IQ in the WAIS tests were kept over time irrespective of the ageing of the patients, to give a representative view of the patients' development over time.…”

“…1 HSCT is currently the only treatment in clinical use for late-juvenile and adult MLD, but the long-term results that have been published are few and inconclusive. [6][7][8][9][10][11][12][13] …”

Improvement of White Matter Changes on Neuroimaging Modalities After Stem Cell Transplant in Metachromatic Leukodystrophy

“…Deterioration of MRI abnormalities after HSCT has been reported in several patients with MLD, 1,4 with stabilization also reported. 8 Cable et al 9 described 1 case with improvement of MRI abnormalities after HSCT but did not provide detailed imaging; the child was clinically unaffected at the time of the transplant and also received cord blood from an unrelated donor.…”

Efficacy of hematopoietic cell transplantation in metachromatic leukodystrophy: the Dutch experience

“…Hematopoietic cell transplantation (HCT) is a possible treatment, but systematic outcome data are lacking, due to the use of different eligibility criteria and protocols worldwide. [4][5][6][7][8][9][10][11][12] In order to assess HCT efficacy, we evaluated all 35 consecutive MLD patients presenting between 2004 and 2015 in our department, the Dutch Leukodystrophy Referral Center ( Figure 1A). …”