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dc.contributor.authorGreaves, O.
dc.contributor.authorPatel, Amit
dc.date.accessioned2021-03-08T06:18:42Z
dc.date.available2021-03-08T06:18:42Z
dc.date.issued2020en
dc.identifier.citationGreaves O, Patel A. The long-term safety and efficacy of autologous haematopoietic stem cell transplantation for relapsing-remitting multiple sclerosis indirectly compared to alemtuzumab: a systematic review. Bone Marrow Transplantation. 2020;55(SUPPL 1):220-1.en
dc.identifier.urihttp://hdl.handle.net/10541/623766
dc.description.abstractBackground: Multiple Sclerosis (MS) is a chronic, progressive, central neurological disease mediated by autoimmunity. Despite availability of anti-inflammatory drugs such as alemtuzumab, disease progression still occurs with minimal initial reversal of symptoms. Autologous haematopoietic stem cell transplantations (aHSCT) for treatment of MS has seen more dramatic reversal in symptoms but have not been previously directly compared to alemtuzumab. Methods: Systemic review of cohort studies and randomised control trials (RCTs) of Relapsing Remitting MS (RRMS) patients treated with alemtuzumab or aHSCT. Results: aHSCT. A total of 144 studies met the search criteria. After application of eligibility criteria and removal of duplicate data, six studies including 277 patients with RRMS, who failed initial DMTs, were included in the review. All patients were initially alemtuzumab naïve. Mean baseline EDSS was 1.5-6.3. Three studies used myelo- and lympho-ablative BEAM-ATG conditioning; the others used lympho-ablative cyclophosphamide (50mg/kg/day for 3-5 days) with ATG (or alemtuzumab in a minority of patients). Both rabbit and horse ATG were used with dosing between 2.5-10mg/kg/day for 2 days or 0.5-1.5mg/ kg/day for 5 days. The available data showed a mean EDSS reduction from a baseline of 3.89 (3sf) to 2.96 at five-year follow-up. Studies with lower pre-aHSCT EDSS experienced the greatest reduction in EDSS. Event-free survival (EFS) to five years was variable between studies ranging from 0% if high pre-aHSCT EDSS, to 85% if low EDSS preaHSCT. Studies with the lowest initial EDSS experienced higher progression-free survival (PFS) to five years, around 90%. All-cause mortality across the studies was 2.6%; treatment related mortality (TRM) was 0.7%. The percentage of patients retained in the studies after five years stood at only 28.9% compared to the alemtuzumab arm where retention stood at 83.0% (p< 0.001). Comparison of EDSS at five-year follow-up between the two study arms may therefore be misleading due to survivorship bias in the aHSCT arm. Alemtuzumab. A total of 39 studies met the search criteria. After application of eligibility criteria and removal of duplicate data, three studies included 759 patients treated with alemtuzumab: CAM MS223, CARE-MSII, and CAREMSI, were used in the study. Both CAM MS223 and CARE-MSI included treatment naïve patients; CAREMSII (357 patients) included previously DMT exposed patients. Mean EDSS pre-alemtuzumab was 1.9-2.7; only 6 patients had an EDSS >5.0. Peak post-alemtuzumab EDSS reduction occurred at 2 years with the CAM MS223 study; the best mean EDSS reduction was 0.3. The improvements at two years were negated by five years. Mean EDSS across the studies progressed from a baseline of 2.31 (3sf) to 2.34 at five-year follow-up representing a mean increase of 0.03. All-cause mortality across studies was 0.5%; TRM was 0.1%. Conclusions: While it is imperfect to indirectly compare treatments from different studies, EDSS outcome patterns between aHSCT and alemtuzumab differed remarkably. aHSCT, in contrast to alemtuzumab, was associated with the largest magnitude of fall in EDSS that was sustained in the long-term to five years. A direct comparison of aHSCT with alemtuzumab in a RCT seems warranted to confirm these observations of long-term benefit with aHSCT.en
dc.language.isoenen
dc.titleThe long-term safety and efficacy of autologous haematopoietic stem cell transplantation for relapsing-remitting multiple sclerosis indirectly compared to alemtuzumab: a systematic reviewen
dc.typeMeetings and Proceedingsen
dc.contributor.departmentUniversity of Liverpool, Liverpool,en
dc.identifier.journalBone Marrow Transplantationen
dc.description.noteen]


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