Hematopoietic cell transplantation for inherited metabolic diseases: an overview of outcomes and practice guidelines

In this retrospective study, we evaluated the chimerism status and outcome in 58 patients (64 transplants) with non-malignant diseases. Reduced intensity conditioning (RIC) was given in half of the transplants. Mixed chimerism (MC) was defined as 41% recipient cells. Two consecutive samples showing 430% recipient cells were defined as high chimerism (high MC). Patients with high MC and the management of these patients were analyzed in greater detail. The overall survival rate was 87%. In total, 23 transplants were donor chimerism (DC) and 41 transplants showed some degree of MC. The incidence of MC was 78 and 50% after RIC and myeloablative conditioning, respectively (P ¼ 0.04). Acute GVHD of grades II-III was more common in patients with DC (39%) than in patients with MC (8%) (P ¼ 0.002). Owing to high MC, donor lymphocyte infusions were given in 17 cases. The level of MC was reduced in seven cases, unchanged in four cases, increased in one case and there was graft rejection in five cases. A second transplant was carried out in six cases with rejections, five are alive and in remission. We conclude that patients with non-malignant diseases, who develop MC after transplant have less acute GVHD. Despite the high incidence of MC, overall survival is promising.

Section: Discussionmentioning

confidence: 93%

Section: Management Of Patients With High MCmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Allogeneic hematopoietic SCT in patients with non-malignant diseases, and importance of chimerism

Svenberg

Mattsson

Ringdén

et al. 2009

“…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. 9,25,26 One of our patients developed mixed chimerism, but the available donor-derived cells provided enough enzyme to normalize the peripheral levels of ARSA. This finding is concurrent with the experience of HSCT for Gaucher's disease, where a stable mixed chimerism is sufficient for an excellent clinical outcome.…”

Section: Discussionmentioning

confidence: 99%

Hematopoietic SCT: a useful treatment for late metachromatic leukodystrophy

Solders

Martin

Andersson

et al. 2014

In metachromatic leukodystrophy (MLD), the deficiency of the lysosomal enzyme arylsulfatase A (ARSA) leads to demyelination in the central and peripheral nervous system and ultimately to death. Allogeneic hematopoietic SCT (HSCT) is currently the only treatment for adult and late-onset juvenile MLD, although it is still in question because of insufficient follow-up. We wanted to determine whether HSCT could halt the progression of adult and late-onset juvenile MLD. Four treated unrelated patients and three untreated siblings were included in the study, and followed regularly for up to 18 years after transplantation. The patients were assessed from clinical examination, ARSA enzyme levels, magnetic resonance imaging of the brain and neuropsychological and neurophysiological tests. In the treated patients, ARSA levels were normal up to 18 years after transplantation. The parameters evaluated stabilized and remained stable after a latency period of 12-24 months. Two patients live normal lives, partially in a protected environment. The other two patients stabilized at a low cognitive and functional level. One of the controls is demented, one is in a vegetative state and one died. We conclude that, in comparison with their untreated siblings, HSCT halted the progression of the disease in our treated patients.

“…Previous reports of MLD and other leukodystrophies have made recommendations to transplant patients in an early age and disease to prevent serious neurological damage. 25,[35][36][37] In patient D, MRI showed progression of white matter lesions in the period of lower enzyme levels but remained stable during further follow-up. DLI was necessary to convert mixed chimerism into complete donor chimerism, resulting in higher levels of ARSA and stabilization of cerebral progression.…”

Section: Discussionmentioning

confidence: 99%

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

Hosson

Warrenburg

Preijers

et al. 2010

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.