Autologous hematopoietic stem cell transplantation (aHSCT) appears to be rather safe and effective method for pediatric patients with severe MS. We aimed to create a model of organization of care for children with severe refractory multiple sclerosis based on multidisciplinary and multicenter approach. Taking into account the results of the analysis of organ toxicity and late effects, efficacy of disease control in childhood and long-term outcomes, we have established the priorities: in-time intensive treatment for children with MS, minimization of its toxicity and achieving the long-term effect.
Fourteen children with MS received aFiSCT from January 2010 to May 2018. Gender: females - 10, males - 4. Mean duration of MS prior aHSCT was 22.7±8.4 months (mean age of MS onset was 12.7±2.1 years old). All patients had severe refractory MS. They were treated with corticosteroids, interferons, plasmapheresis and mitoxantron with negative results. Mean baseline EDSS before the start of mobilization was 4.8±1.4. PBSC mobilization - Cyclophosphamide (Cy) 2000 mg/sq.m. with mesna, Filgrastim start on day +7 from Cy, PBSC harvest with the help of apheresis. Target cells No. - 2xl06 CD34+ cells on kg of body weight. Interval from Cy infusion and conditioning start - 3 weeks. Conditioning regimen, Cy 200 mg/kg divided in 4 days: -5,-4,-3,-2 d, hATG 160 mg/kg divided in 4 days: -2,-l,+l,+2 d, PBSC reinfusion on day 0, G-CSF stimulation from day +5 (5 mkg/kg). All patients received at least 2 x 106/kg CD34+ cells (mean 4.3 x 106±2.6 x 106). aHSCT as well as pre- and post-transplant care was done by multidisciplinary team which included both transplant specialists and neurologists.
All patients are alive. Mean time to engraftment - 11 ±1.6 days. 11 patients experienced culture negative fever, one patient - cystitis, and one patient had CMV reactivation within 100 days of the transplant. No patient experienced an EDSS increase post-HSCT above baseline, and all patients improved. Mean improvement of EDSS was 2.8±1.2 during the first 60 days after aHSCT (fast recovery) - recover even after mobilization. In-time transplanted patients improved better. Improvement was confirmed by immunological data (increasing of immune regulation index and T-regs in comparison with the baseline). Median follow-up period was 48 months (8-72 months). 5 patients (36%) experienced exacerbations (both neurological and MRI) in median of 3 years (1-6 years) after aHSCT. No onsets of secondary autoimmune disease and malignancies were observed. Cardiovascular late effects were seen in 6 patients and endocrine - in 3 patients (all females). All these late effects were successfully treated. Our experience in Cy therapy without aHSCT - 2 patients received mobilization without subsequent HSCT and no relapses at long-term follow-up (9 and 8 years).
AHSCT for pediatric patients with severe MS appears to be rather safe and effective method. Even if progression was stopped for a few years, it was considered as a success. Late effects found in patients were successfully treated. We provide a best care for these patients in both childhood and adulthood by transferring them to adult Center. Multicenter and multidisciplinary model of care for children with severe refractory MS was established (Picture 1.).