Autologous hematopoietic stem cell transplantation in multiple sclerosis

Abstract

The emerging evidence on this therapeutic approach in MS indicates that the largest benefit/risk profile form this therapeutic approach can be obtained in patients with aggressive MS with a relapsing-remitting course and who have not yet accumulated a high level of disability.

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis

“…Besides these situations, however, patients with an EDSS score <6 (ambulatory without aid) are the most appropriate candidates for AHSCT and, on the basis of published evidence 60,57 and our clinical experience, we suggest that patients with established EDSS scores ≥7 are at high risk of complications and treatment failure, so are not appropriate candidates for AHSCT.…”

“…In this study, a higher EDSS score was significantly associated with poorer overall survival (HR 2.03 per EDSS point). Similarly, in a meta-analysis, a baseline EDSS score >6 was significantly associated with a higher treatment-related mortality (P = 0.013) 57 . These associations can be explained by a high incidence of comorbidities (such as urinary tract infections and chronic lung disease) and their attendant complications in non-ambulatory patients, 80 as well as a higher risk of death from progression of MS.…”

Advising patients seeking stem cell interventions for multiple sclerosis

“…Overall, however, the greatest risks are associated with myeloablative procedures due to neutropenic sepsis and haemorrhage in the context of thrombocytopaenia; these contribute disproportionately to the estimated 2%–3% risk of transplant-related mortality associated with AHSCT 25. In general, patients with MS face similar regimen-related risks as patients undergoing transplantation for other indications but a number of complications occur either more frequently or more severely, including increased incidence of urinary tract infections, transient worsening of MS-related symptoms due to febrile neutropaenia or infection (pseudorelapse), reactivation of human herpes viruses following CD34 selected grafts or antithymocyte globulin treatment, as well as the additive effect on disability of neurotoxic conditioning regimens 18.…”

Intense immunosuppression followed by autologous haematopoietic stem cell transplantation as a therapeutic strategy in aggressive forms of multiple sclerosis

“…Therefore, our experience (unpublished data), is completely in agreement with the more recent studies that demonstrate that aHSCT is extremely effective in reducing long term disease activity in aggressive MS patients. Recently a meta-analysis evaluating all the published studies from 1995 to 2016 was published, including 764 patients with a severe treatment refractory MS form of disease 39 . Pooled rate of progression was 17.1% at 2 years and 23.3% at 5 years but a lower progression rate was significantly associated with a high proportion of RR MS patients.…”

“…In line with this hypothesis, recent data indicate that neurological deterioration in the progressive phase might be driven by compartmentalized inflammation behind the blood-brain barrier, opening the possibility that targeting inflammation might reduce accrual of neurological disability, as suggested by recent trials of B-cells targeted therapies 42,43. However, controlled evidence of the efficacy of aHSCT for progressive MS is still lacking and more data from randomized clinical trial are needed. Moreover, data from published studies 8 and EBMT and CIBMTR registries 2 , clearly indicate that a progressive course of the disease and a higher EDSS score are associated with an increased transplant mortality risk, raising concerns about the safety profile of AHSCT in progressive MS patients.…”