A clinical research consortium sponsored by NIAID and JDRF
Bowen JD, Sayre P, Stüve O, Wundes A, Kraft GH, Hutton GJ, Openshaw H, Forman SJ, Frohman EM, Griffith LM, Muraro PA, Racke MK, Popat U, Nash RA
Objective: To determine if high dose immunosuppressive therapy/ autologous hematopoietic stem cell transplantation (HDIT/AHSCT) induces sustained remissions and prevents loss of neurological function in poorly-responsive relapsing-remitting MS (RRMS).
Background: HDIT/AHSCT may induce sustained remissions in patients with autoimmune disease. In a previous clinical trial of HDIT/AHSCT of 26 patients with advanced progressive-type MS (median EDSS 7.0), estimated progression rate of the cohort was 37% at 6 years; response was best in earlier disease stages. Since degenerative changes may contribute to loss of neurological function in progressive-type MS, HDIT/AHSCT in RRMS was studied.
Design/Methods: Phase II clinical trial of HDIT/AHSCT with high-dose chemotherapy (BEAM) and antithymocyte globulin (ATG) in RRMS (EDSS 3.0-5.5; >2 relapses on treatment and EDSS worsening over past year), followed by transplantation with autologous CD34+-selected cells from G‑CSF mobilized blood. Sample size: 25 patients with 5-year follow-up.
Results: Seven MS patients demonstrating neurological decline with ongoing relapses on standard therapy underwent HDIT/AHSCT (baseline EDSS range 3.5-5.0; median 5.2 x 106 CD34+ cells/kg, purity 95.2%). Hematological recovery occurred 11-13 days post procedure and patients were discharged to outpatient setting. In the median follow-up of 9.5 months (range 2-21), there were no further relapses and neurological functioning measured by EDSS for six patients was stable (n=2), improved up to 2 points (n=3), worsened by 0.5 points (n=1). Brain MRI imaging did not reveal new or enhancing lesions. Post-transplantation pseudo-GVHD (n=1), pseudo-relapse (n=1) and MRSA infection (n=1) occurred transiently, but no other unexpected or severe toxicities. Six more patients met eligibility and are pre-transplant.
Conclusion/relevance: These results for HALT MS in RRMS poorly-responsive to conventional treatment are encouraging. The first 7 patients tolerated treatment well. Additional follow up will be needed to confirm the stabilization of disease and neurological improvement suggested for this severely affected population.
Funding: Supported and conducted by ITN (study ITN033AI), sponsored by NIAID.
