Autologous stem cell transplant may improve PFS, OS in multiple sclerosis
Individuals who underwent autologous haematopoietic stem cell transplantation (AHSCT) as a treatment for multiple sclerosis (MS) had improved progression-free survival (PFS) and overall survival (OS) five years post-transplant, a recent retrospective, observational study found.
At 5 years after AHSCT, 46 percent of MS patients (95 percent confidence interval [CI], 42–54 percent) were progression-free, with progression defined as a 1 point increase in Expanded Disability Status Scale (EDSS) score at 12 months or 0.5 point increase if baseline EDSS ≥5.5 compared with pretransplant. [JAMA Neurol 2017;doi:10.1001/jamaneurol.2016.5867]
PFS appeared to differ according to type of MS with patients with relapsing MS having a PFS of 73 percent while those with secondary progressive MS had a PFS of 33 percent at 5 years after AHSCT. OS at 5 and 10 years post-transplant was 93 and 84 percent, respectively.
Multivariate analyses showed that older age, progressive vs relapsing MS, and more than two treatments prior to AHSCT were associated with poorer PFS (hazard ratio [HR], 1.03, 95 percent CI, 1.00–1.05; p=0.02, HR, 2.33, 95 percent CI, 1.27–4.28; p=0.007, and HR, 1.65, 95 percent CI, 1.10–2.47; p=0.008, respectively), while higher baseline EDSS score was associated with poorer OS over time (HR, 2.03, 95 percent CI, 1.40–2.95; p<0.001 per EDSS point).
“By not imposing any criteria to select a disease phenotype, we were able to demonstrate significant associations of [baseline EDSS score, older age, or prior number of immunosuppressive or modulatory treatments] with worse outcomes,” said the researchers.
“... The multivariate statistics indicate that the profile of a patient who is more likely to survive without neurological progression is that of a younger individual with relapsing MS who has failed no more than two disease-modifying treatments and has not reached high levels of disability,” they said, and called for a randomized clinical trial that compares AHSCT and currently-approved, effective therapies in patients with highly active relapsing MS.
Researchers obtained data of 281 individuals (median age, 37 years, 58.4 percent female) from 25 centres in 13 countries who were treated with AHSCT for MS between January 1995 and December 2006. Patients were followed-up for a median 6.6 years.
The most common form of MS was secondary progressive MS, accounting for 66.2 percent of the cohort (n=186). About 61 percent (n=171) of patients had received two or more treatments prior to AHSCT. There were 37 deaths from any cause during the follow-up period and eight transplant-related deaths that occurred within 100 days of transplant.
While the number of transplant-related deaths in the study was high (2.8 percent), a retrospective analysis of the European Blood and Marrow Transplant registry in 2007 showed a reduction in transplant-related deaths over time (7.3 percent in 1995–2000 to 1.3 percent in 2001–2007). [Lancet Neurol 2008;7:626-636]
This may be due to improved patient selection for the procedure and a reduction in the use of intensive conditioning regimens, said the researchers of the present study.