This paper describes a case series of 151 patients with MS treated at a single US hospital. 22 (15 %) patients were conditioned with cyclophosphamide and alemtuzumab, with the remainder [129 (85 %)] receiving cyclophosphamide and anti-thymocyte globulin before autologous transplantation of unselected hemopoietic stem cells. 123 (81 %) had relapsing-remitting and 28 (19 %) had secondary progressive MS. Fifty five patients were treated on the study protocol and met the following criteria: relapsing-remitting MS, Extended Disability Status Scale (EDSS) scores of between 2.0 and 6.0, received treatment with at least 1 FDA approved drug [mostly beta-interferon but also natalizumab (27 %) and fingolimod (8 %)], at least two corticosteroid treated relapses within the last year or one corticosteroid treated relapse and gadolinium enhancing lesions on MRI. Ninety six patients were treated off the study protocol on a compassionate basis for reasons including having secondary progressive disease, an EDSS score greater than 6.0 or particularly disabling disease. The patients had regular EDSS, Multiple Sclerosis Functional Composite (MSFC), Neurologic Rating Scale (NRS) and short form 36 quality of life assessments as well as MRI scans with gadolinium and were followed up for a median of 2 years.
There were no deaths during the treatment. 14 (9 %) patients had a post-transplant autoimmune adverse event [immune-mediated thrombocytopenia (ITP), hypothyroidism or hyperthyroidism] with the proportion being higher in the group receiving alemtuzumab compared with anti-thymocyte globulin (9 % compared with 4 %).
The primary end point was change in EDSS score. The mean EDSS score for the whole group improved significantly after transplant, with 50 % and 64 % of patients demonstrating an improvement in EDSS score of greater than 1.0 point at 2 and 4 years, respectively. NRS and MSFC scores also improved significantly after treatment. 80 % and 68 % of patients had no new relapses, gadolinium enhancing lesions on MRI or increase in their EDSS score (disease free survival) at 2 and 4 years, respectively. 89 % and 80 % of patients had no new relapses at 2 and 4 years, respectively. A subgroup analysis suggested no benefit in patients with progressive disease not having relapses before treatment.
Comment: This study was a case series and not a trial and contained a heterogeneous mix of patients with both relapsing and progressive disease (despite the title). A significant proportion of patients (63 %) were treated off study protocol on a compassionate basis and the majority of patients had not received standard high efficacy treatments. This together with the varying conditioning regime including the use of alemtuzumab exemplifies the difficulties in reaching firm conclusions on the effect of aHSCT. On a positive note, there were no deaths and a relatively low proportion of treatment related complications when compared to other studies, which is likely to be due to the use of a nonmyeloablative conditioning regime. EDSS scores were presented as whole group averages, however, there was a significant improvement in EDSS score for the majority of patients and 80 % of patients achieved disease free survival at 2 years.
Burt RK et al. (2015) JAMA 313(3):275–284.