A clinical research consortium sponsored by NIAID and JDRF
Hutton GJ, Bowen JD, Forman SJ, Frohman EM, Griffith LM, Kraft GH, Openshaw H, Popat U, Racke M, Sayre P, Stüve O, Wundes A, Nash RA, Muraro P
Objective: To determine if high dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation (HDIT/AHSCT) induces sustained remissions and prevents loss of neurological function in active relapsing-remitting MS (RRMS).
Background: HDIT/AHSCT has been assessed as a possible new therapeutic strategy in severe forms of MS. Small uncontrolled studies showed that about 60-70% of treated patients do not worsen in the follow-up period of at least 3 years. Responses were best in those with earlier disease stages. Since degenerative changes may contribute to loss of neurological function in progressive MS, HDIT/AHSCT is being studied in RRMS.
Methods: HALT-MS is an ongoing phase II clinical trial of HDIT/AHSCT with high dose chemotherapy (BEAM) and antithymocyte globulin (ATG) in active RRMS (EDSS 3.0-5.5; ≥2 relapses on treatment and EDSS worsening over past year). This is followed by transplantation with autologous CD34+-selected cells from G-CSF mobilized blood. Sample size: 25 patients with 5 year follow-up.
Results: Nine RRMS patients underwent HDIT/AHSCT (mean EDSS 4.3, median 4.3 x 106 CD34+ cells/kg, purity 95.2%). Hematologic recovery occurred 11-13 days post-transplant and patients were discharged to outpatient setting. In the median follow-up of 11.5 months (range 1-23), there were no further relapses and EDSS was stable in 2, improved up to 2 points in 3 and worse by 0.5 points in 1 subject. Brain MRI did not reveal any new or enhancing lesions. Post-transplantation complications included pseudo-GVHD (n=1), pseudo-relapse (n=1) and MRSA infection (n=1), but no other unexpected or severe toxicity. Six more patients have met eligibility and are pre-transplant.
Conclusion: These early results for HALT-MS in active RRMS poorly-responsive to conventional treatment are encouraging with suggestion of stabilization of disease and neurologic improvement. The first 9 patients tolerated treatment well. Additional clinical and radiologic follow-up and mechanistic studies are ongoing.
Funding: Supported and conducted by ITN (study ITN033AI), sponsored by NIAID.
