One of the possible options for the treatment of MS at present is a high-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation (HIST-AHSCT), which is a highly effective treatment for patients with relapsing-remitting MS.
This method of MS treatment was introduced in 1997. Significant complications and mortality associated with HIST-ATHSC is an obstacle to broad use of this method. The risk is even greater in patients with advanced disease, long duration of previous treatment and aggressive forms of MS.
Despite toxicity certain progressive cases of MS are still an indication for HIST-autoHSCT.
Most commonly used conditioning regimens for multiple sclerosis include high-dose cyclophosphamide. One of the options to reduce cyclophosphamide-related toxicity and dose is addition of fludarabine. Fludarabine is a cytostatic drug, an antimetabolite from the group of purine antagonists. It has a pronounced immunosuppressive activity and no overlapping toxicity with cyclophosphamide. The study will evaluate the safety and efficacy of this combination.
Age 18-65;
1.0-6.5 points on the EDSS scale (for MS);
Length of illness - any;
Disease progression during the last 6 months while taking drugs of 1st and 2nd lines;
Moderate or severe cardiac dysfunction, left ventricular ejection fraction <50%
Moderate or severe decrease in pulmonary function, FEV1 <70% or DLCO<70% of predicted
Respiratory distress >grade I
Severe organ dysfunction: AST or ALT >5 upper normal limits, bilirubin >1.5 upper normal limits, creatinine >2 upper normal limits
Single group
Fludarabine Phosphate for Injection
DrugIntravenous injection of fludarabine phosphate at a dose of 30 mg/m2 from day -5 to day -2 of immunoablative conditioning regimen.
Multiple sclerosis progression free survival
To evaluate safety and effectiveness of immunoablative conditioning regimen FluCy200 in patients with refractory multiple sclerosis after AHSCT.
Cumulative incidence of mortality
Death from any cause after AHSCT
To evaluate adverse effects after FluCy200 conditioning regimen
Toxicity based NCI CTCAE ver.5.0, including analysis of severe bacterial, fungal and viral infections incidence
Quality of life status 1
Multiple sclerosis-specific questionnaire - HADS (Hospital Anxiety and Depression Scale) before and after AHSCT: 0-7 points - normal; 8-10 - subclinically expressed anxiety/depression; 11-21 - clinically expressed anxiety/depression.
Quality of life status 2
Multiple sclerosis-specific questionnaire - The Short Form-36 (SF-36) before and after AHSCT: The SF-36 consists of 36 questions grouped into eight scales: physical functioning, role-physical functioning, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. The indicators of each scale are compiled in such a way that the higher the value of the indicator (from 0 to 100), the better the score on the chosen scale. Of these, two parameters are formed: the psychological and physical components of health.
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