High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS

Abstract

Objective:To evaluate the safety, efficacy, and durability of multiple sclerosis (MS) disease stabilization after high-dose immunosuppressive therapy (HDIT) and autologous hematopoietic cell transplantation (HCT).Methods:High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT-MS) is a phase II clinical trial of HDIT/HCT for patients with relapsing-remitting (RR) MS who experienced relapses with disability progression (Expanded Disability Status Scale [EDSS] 3.0–5.5) while on MS disease-modifying therapy. The primary endpoint was event-free survival (EFS), defined as survival without death or disease activity from any one of: disability progression, relapse, or new lesions on MRI. Participants were evaluated through 5 years posttransplant. Toxicities were reported using the National Cancer Institute Common Terminology Criteria for Adverse Events (AE).Results:Twenty-five participants were evaluated for transplant and 24 participants underwent HDIT/HCT. Median follow-up was 62 months (range 12–72). EFS was 69.2% (90% confidence interval [CI] 50.2–82.1). Progression-free survival, clinical relapse-free survival, and MRI activity-free survival were 91.3% (90% CI 74.7%–97.2%), 86.9% (90% CI 69.5%–94.7%), and 86.3% (90% CI 68.1%–94.5%), respectively. AE due to HDIT/HCT were consistent with expected toxicities and there were no significant late neurologic adverse effects noted. Improvements were noted in neurologic disability with a median change in EDSS of −0.5 (interquartile range −1.5 to 0.0; p = 0.001) among participants who survived and completed the study.Conclusion:HDIT/HCT without maintenance therapy was effective for inducing long-term sustained remissions of active RRMS at 5 years.ClinicalTrials.gov identifier:NCT00288626.Classification of evidence:This study provides Class IV evidence that participants with RRMS experienced sustained remissions with toxicities as expected from HDIT/HCT.

Manufacture of Autologous CD34+ Selected Grafts in the NIAID-Sponsored HALT-MS and SCOT Multicenter Clinical Trials for Autoimmune Diseases

“…For HALT-MS, 24 of 25 subjects mobilized successfully with G-CSF and prednisone; 1 individual required subsequent mobilization using cyclophosphamide [1,2]. For SCOT, of 34 subjects treated with G-CSF and prednisone for mobilization, 2 needed a second course of G-CSF and prednisone, whereas a third required cyclophosphamide to achieve successful mobilization.…”

“…Subjects were mobilized for PBSC collection using G-CSF and prednisone, for the HALT-MS and SCOT studies, as described [1,2,6]. …”

“…Clinical outcomes for the Phase II study in MS (HALT-MS) [1,2] and the prospective randomized study versus standard care for scleroderma (SCOT) [3] are available.…”

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis

“…The conditioning regimens with the strongest traction within each intensity category are cyclophosphamide and ATG (low intensity), BEAM and ATG (intermediate intensity) and cyclophosphamide, busulfan and ATG (high intensity). In the absence of evidence from randomized comparisons, we endorse the preferential use of BEAM and ATG -the scheme that is specifically recommended for the treatment of MS in the EBMT guidelines 56 -by virtue of its extensive track record that indicates good safety and high efficacy 14,73 , and of the opportunity it provides for comparisons across data sets.…”

Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases

“…6,7 Similar developments happened worldwide and there have been a large number of retrospective and prospective studies in a wide range of ADs. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] More recently, randomized controlled trials have reported confirming proof of principle in several ADs. [28][29][30][31][32] Despite international guidelines and recommendations, the uptake of HSCT in AD has been highly variable, both geographically and in respect to type of AD.…”