By Lucy Piper
Intensifying current transplant conditioning to remove rather than suppress immune cells ahead of autologous haematopoietic stem cell transplantation (aHSCT) may result in long-term remission of multiple sclerosis (MS), phase II trial findings show.
Among 24 patients with aggressive treatment-refractory MS, 69.6% were alive and free of MS activity 3 years after undergoing immunoablation with busulfan, cyclophosphamide and rabbit anti-thymocyte globulin followed by transplantation of CD34-selected aHSCs.
Being free of MS activity included having no relapses, no new lesions on magnetic resonance imaging (MRI) scans and a sustained stabilisation of Expanded Disability Status Scale (EDSS) score. All this in the absence of disease-modifying drugs, note the researchers.
Led by Harold Atkins (The Ottawa Hospital, Ontario, Canada), they add in The Lancet that over the median follow-up of 6.7 years, in nine patients "whole brain atrophy slowed to a rate associated with normal aging".
The researchers note, however, that the 70% success rate despite the lack of further inflammatory activity and lesions was primarily due to continuing progression of disability in seven patients.
These patients "lacked detectable clinical and MRI evidence of inflammatory activity, suggesting dissociation of the process responsible for advancing disability from ongoing focal inflammatory lesions," they write.
"Optimally stopping further progression requires targeting patients when they still have active [central nervous system] inflammation."
In a related comment, Jan Dör (Charité-Universitätsmedizin Berlin, Germany) describes the findings as "impressive" and says that they "seem to outbalance any other available treatment for multiple sclerosis".
Before transplantation, the patients had experienced a total of 167 relapses over 140 patient-years and all had progressive loss of neurological function.
But afterwards, none of the 23 surviving patients experienced a relapse over 179 patient-years of follow-up and 70% had no further EDSS progression, while EDSS improvement was seen in 40% after 7.5 years. After 3.0 years, 37% of patients were able to return to work or school having previously received disability benefits. The one patient who died did so from transplantation-related hepatic necrosis and sepsis and 33% of patients had a moderate toxic effect as a result of treatment.
Atkins stresses the need for caution before widespread adoption of this type of treatment, given that their study sample was small and there was no control group.
"Achieving the best outcomes for autologous haematopoietic stem-cell transplantation requires experience for patient selection and specialised care to minimise procedural risks," he says.
Dör agrees that this study is unlikely to change the approach to MS treatment in the short term; "mainly because the mortality rate will still be considered unacceptably high", he says.
"Over the longer term, however, and in view of the increasing popularity of using early aggressive treatment, there may be support for considering aHSCT less as a rescue therapy and more as a general treatment option, provided the different protocols are harmonised and optimised, the tolerability and safety profile can be further improved, and prognostic markers become available to identify patients at risk of poor prognosis in whom a potentially more hazardous treatment might be justified."
Licensed from medwireNews with permission from Springer Healthcare Ltd. ©Springer Healthcare Ltd. All rights reserved. Neither of these parties endorse or recommend any commercial products, services, or equipment.
Lancet 2016; Advance online publication