HSCT after natalizumab

Mariottini A, Innocenti C, Forci B, Magnani E, Mechi C, Barilaro A, Nistri R, Fani A, Saccardi R, Massacesi L, Repice AM. Safety and efficacy of autologous hematopoietic stem cell transplantation following natalizumab discontinuation in aggressive Multiple Sclerosis. Eur J Neurol. 2018 Nov 10. doi: 10.1111/ene.13866. [Epub ahead of print]

BACKGROUND: Natalizumab (NTZ) is a highly effective treatment for relapsing-remitting multiple sclerosis (RRMS), but its withdrawal is often followed by disease reactivation or rebound, even if other disease-modifying treatments (DMTs) are administered. In this study, for the first time, safety and efficacy of autologous hematopoietic stem cell transplantation (aHSCT) performed following NTZ discontinuation was retrospectively compared with conventional DMTs.
METHODS: Patients with RRMS treated with NTZ and who discontinued the drug after at least six administrations and with at least six months of follow-up were included. Patients underwent aHSCT after a minimum period of six months following NTZ withdrawal, receiving in the meanwhile cyclophosphamide or corticosteroids, or received other DMTs approved for MS (control group) after an adequate wash-out period. Both haematological and neurological follow-up were assessed according to standard policies.
RESULTS: Fifty-two patients were included, 11 who received aHSCT and 41 DMTs. Baseline clinical and demographic characteristics were similar between the two groups. No fatality or life-threatening complications, including Progressive Multifocal Leukoencephalopathy, were observed. At three years following NTZ discontinuation no evidence of disease activity was reported in 54.5% of the patients in the aHSCT group compared to 11.5% of those in the DMT group (p=0.0212); disease reactivation in the aHSCT patients was observed only during wash-out/bridging therapy and after aHSCT 100% of the cases were free from disease activity.
CONCLUSION: These data suggest that an aggressive therapy should be established after NTZ with the shortest possible wash-out period. AHSCT after six months from NTZ withdrawal seems safe.

If you are not having a sub clinical infection of JC virus, conversion to a depleting antibody is safe. However there have been cases of fatality after alemtuzumab, where there was carry over infection. So the risks for HSCT are similar so ensure you don’t have sub clinical PML before starting

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