BACKGROUND: Autologous haematopoietic stem cell transplantation (HSCT) is a viable option for treatment of aggressive multiple sclerosis (MS). No randomised controlled trial has been performed, and thus, experiences from systematic and sustained follow-up of treated patients constitute important information about safety and efficacy. In this observational study, we describe the characteristics and outcome of the Swedish patients treated with HSCT for MS.
METHODS:Neurologists from the major hospitals in Sweden filled out a follow-up form with prospectively collected data. Fifty-two patients were identified in total; 48 were included in the study and evaluated for safety and side effects; 41 patients had at least 1 year of follow-up and were further analysed for clinical and radiological outcome. In this cohort, 34 patients (83%) had relapsing-remitting MS, and mean follow-up time was 47 months.
RESULTS: At 5 years, relapse-free status was 87%; MRI event-free status 85%; expanded disability status scale (EDSS) score progression-free status 77%; and disease-free status (no relapses, no new MRI lesions and no EDSS progression) 68%. Presence of gadolinium-enhancing lesions prior to HSCT was associated with a favourable outcome (disease-free status 79% vs 46%, p=0.028). There was no mortality. The most common long-term side effects were herpes zoster reactivation (15%) and thyroid disease (8.4%).
CONCLUSIONS: HSCT is a very effective treatment of inflammatory active MS and can be performed with a high degree of safety at experienced centres.
However it is not always plain sailing so do your homework
Ghavamzadeh A, Alimoghaddam K, Ghaffari F, Derakhshandeh R, Jalali A, Jahani M. Twenty years of experience on stem cell transplantation.Red Crescent Med J. 2013;15:93-100
BACKGROUND:Haematopoietic stem cell transplantation (HSCT) is a new window to therapy of many diseases. From March 1991 through April 2011, a total of 3237 HSCT were performed in the Haematology-Oncology and Stem Cell Transplantation Research Center. Here we report 20 years experience of HSCT.
PATIENTS AND METHODS: Totally, 3237 patients were undergone HSCT. Of these transplants, 2205 were allogeneic stem cell transplantation, 1016 autologous and 16 syngeneic.
RESULTS: About 78.2% of the patients (2530 of 3237) remained alive between one to 211 months after stem cell transplantation. Nearly, 21.8% (707) of our patients died after stem cell transplantation. The main causes of death were relapse, infection, haemorrhagic cystitis, graft-versus- host disease and etc.
CONCLUSIONS: HSCT has been successfully adapted in routine clinical care.
Atkins HL, Freedman MS. Haematopoietic stem cell therapy for multiple sclerosis: top 10 lessons learned. Neurotherapeutics. 2013;10(1):68-76.
The patient’s own stem cells are harvested and stored temporarily while high doses of chemotherapy and biologics are used to destroy the auto-destructive immune system. The immune system is regenerated from the infused autologous hematopoietic stem cells. Increasing clinical experience has refined patient selection criteria and management in the peri-transplant period leading to a reduction in treatment-related complications. HSCT, when used to treat patients with aggressive highly active multiple sclerosis, can reduce or eliminate ongoing clinical relapses, halt further progression, and reduce the burden of disability in some patients, in the absence of chronic treatment with disease-modifying agents. The top 10 lessons learned from the growing experience using HSCT for the treatment of multiple sclerosis are discussed.
Lesson 2: Increasing Experience Using HSCT for Patients with MS Reduces Morbidity and Mortality
Lesson 3: CNS Toxicity of Very High-Dose Regimens may Adversely Influence Outcomes
Lesson 4: HSCT is More Likely to be Effective for MS Patients with Active CNS Inflammation
Lesson 5: HSCT is Effective at Controlling Inflammatory MS Activity, with Higher Response Rate Observed with More Intense Conditioning Regimens
Lesson 6: HSCT can Result in Long-Term Progression-Free Outcomes
Lesson 7: The Recovery of Functional Ability can Occur in HSCT Recipients
Lesson 8: Tolerance can Develop Resulting in Obliteration of Autoimmunity while Preserving Protective Immunity
Lesson 9: The Reconstituted Immune System Retains a Predisposition to Autoimmunity
Lesson 10: Information on the Economics and Health Resource Usefulness of HSCT for MS Needs to be Gathered
Bowen JD, Kraft GH, Wundes A, Guan Q, Maravilla KR, Gooley TA, McSweeney PA, Pavletic SZ, Openshaw H, Storb R, Wener M, McLaughlin BA, Henstorf GR, Nash RA.Autologous haematopoietic cell transplantation following high-dose immunosuppressive therapy for advanced multiple sclerosis: long-term results. Bone Marrow Transplant. 2012;47(7):946-51.
The purpose of the study was to determine the long-term safety and effectiveness of high-dose immunosuppressive therapy (HDIT) followed by autologous hematopoietic cell transplantation (AHCT) in advanced multiple sclerosis (MS). TBI, CY and anti-thymocyte globulin were followed bytransplantation of autologous, CD34-selected PBSCs. Neurological examinations, brain magnetic resonance imaging and cerebrospinal fluid (CSF) for oligoclonal bands (OCB) were serially evaluated. Patients (n=26, mean Expanded Disability Status Scale (EDSS)=7.0, 17 secondary progressive, 8 primary progressive, 1 relapsing/remitting) were followed for a median of 48 months after HDIT followed by AHCT. The 72-month probability of worsening ≥1.0 EDSS point was 0.52 (95% confidence interval, 0.30-0.75). Five patients had an EDSS at baseline of ≤6.0; four of them had not failed treatment at last study visit (one of them had failed). OCB in CSF persisted with minor changes in the banding pattern. Four new or enhancing lesions were seen on MRI, all within 13 months of treatment. In this population with high baseline EDSS, a significant proportion of patients with advanced MS remained stable for as long as 7 years after transplant. Non-inflammatory events may have contributed to neurological worsening after treatment. HDIT/AHCT may be more effective in patients with less advanced relapsing/remitting MS.