Autologous Haematopoietic Stem Cell Transplant In Patients With Neuromyelitis Optica

Background: Neuromyelitis Optica (NMO) is an idiopathic demyelinating and neurodegenerative disease of the central nervous system, preferentially affecting the optic nerves and spinal cord.  Frequent attacks result in significant morbidity with a 5-year survival rate of only 68%.  Treatments for this disease are highly toxic and only minimally effective.

Objectives: Given the immune mechanisms involved in NMO, the limited impact of existing therapies, and the promising results of recent stem cell transplant trials in multiple sclerosis, we have undertaken a trial of autologous non-ablative stem cell transplantation (AHSCT) in NMO in an effort to see if such treatment can lead to disease remission and freedom from chronic immunosuppressive medication.  Specifically, we hypothesize that this trial will allow us to detect a 50% reduction in the proportion of patients experiencing relapse events over a three year period.  Secondary outcomes include relapse rate, disability status, MRI activity, ophthalmological measures and overall survival.

Methods: This open-label single centre trial was approved by the Calgary Conjoint Health and Research Ethics Board and Health Canada.  Eligible patients are those with a diagnosis of NMO (Wingerchuk 2006), ages 18-65 and EDSS <=6.5 with =>1 relapse in 12 months or =>2 relapses in 24 months despite accepted maintenance therapy.  Using a cyclophosphamide/rituximab/ATG protocol, patients undergo mobilization/harvesting of stem cells followed by conditioning/stem cell infusion 4-8 weeks later. Patients are monitored over 5 years.

Results: Presently, two NMO patients have undergone transplantation.  Patient 1 (28F) was transplanted in May 2011 with a pre-transplant annualized relapse rate (ARR) of 5 in the year before transplant and an entry EDSS of 3.0.  Her only transplant complications were transient asymptomatic febrile neutropenia, volume overload and premature menopause that has now resolved.  Her ARR in the 18 months post-transplant is 0 with an EDSS of 2.0.  Patient 2 (36F), transplanted in April 2012 without any significant acute complications, had a pre-transplant ARR of 4 in the year before transplant and an entry EDSS of 4.5.  She had no significant transplant complications.  Her ARR 6 months post-transplant is 0 with an EDSS of 4.0.

Conclusions: At this early date, it appears that this transplant regimen is both tolerable and effective, with both patients remaining relapse-free and without the need for NMO rescue or maintenance therapy thus far.  If these results are seen over a longer time period and in subsequent patients, AHSCT may prove to be an effective and tolerable strategy for NMO patients.