Autologous hematopoietic stem cell transplantation for Stiff Person Spectrum Disorder: A clinical trial

Objective:To test the hypothesis that autologous non-myeloablative hematopoietic stem cell transplantation (HSCT) is safe and shows efficacy in the treatment of stiff person spectrum disorder (SPSD).Methods:Twenty-three participants were treated in a prospective open-label cohort study of safety and efficacy. Following stem cell mobilization with cyclophosphamide (2 g/m2) and filgrastim (5–-10 ug/kg/day), participants were treated with cyclophosphamide (200 mg/kg) divided as 50 mg/kg IV on day −-5 to day −-2, rATG (thymoglobulin) given IV at 0.5 mg/kg on day −-5, 1 mg/kg on day −-4 and −-3, and 1.5 mg/kg on days −-2, and −-1 (total dose 5.5 mg/kg), and rituximab 500 mg IV on days −-6 and +1. Unselected peripheral blood stem cells were infused on day 0. Safety was assessed by survival and NCI common toxicity criteria for adverse events during HSCT. Outcome was assessed by ≥ 50% decrease or discontinuation of anti-spasmodic drugs and by quality of life instruments.Results:There was no treatment-related mortality. One participant died 1 year after transplant from disease progression. 74% of participants responded, 47% have stayed in remission for a mean of 3.5 years, and 26% did not respond. When compared to non-responders, responders were more likely to have pre-transplant intermittent muscle spasms (16/17 vsversus 0/6), normal reflexes (12/17 vsversus 0/6) and positive cerebrospinal fluid anti-GAD serology (12/14 vsversus 2/6). Compared to responders, non-responders were more likely to have lead pipe rigidity (4/6 vsversus 0/17), and EMG documented simultaneous contraction of agonist / antagonist limb muscles (4/6 vsversus 1/17). Pre-HSCT use of prescription SSRI and or SNRI was more common in those who relapsed or never responded (9/12) compared to those responders who never relapsed (0/11).Conclusion:In this cohort, HSCT was safe, but beneficial effect of HSCT was variable and predominately confined to participants with episodic spasms, normal tendon reflexes, without simultaneous co-contraction of limb agonist antagonist muscles, and who were not taking SSRI or SNRI antidepressants.Classification of eEvidence:This study provides Class IV evidence that for a subset of people with SPSD, autologous non-myeloablative HSCT improves outcomes.Clinical trial registry:ClinicalTrials.gov Identifier: NCT02282514.