Inclusion Criteria:

• - Age 18-65; - 1.0-7.5 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; - An established and confirmed diagnosis of an autoimmune disease in the previous stages of treatment; - Ineffectiveness, inaccessibility or intolerance of Disease-Modifying Therapies; - Relapse after AHSCT.

• - Absence of severe concomitant somatic pathology; - Left ventricular injection fraction > 50%; - Karnofsky Performance Score (KPS) > 30%; - The ability to take oral medications; - Life expectancy is more than 1 month; - Signed informed consent of the patient or legal representatives.

Exclusion Criteria:

• - 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.

• - Creatinine clearance < 60 mL/min.

• - Uncontrolled bacterial or fungal infection at the time of enrollment.

• - Requirement for vasopressor support at the time of enrollment.

• - Karnofsky performans status <30% - Pregnancy.

- Somatic or psychiatric disorder making the patient unable to sign informed consent

Multiple sclerosis (MS) is a chronic progressive autoimmune-mediated inflammatory demyelinating disease of the central nervous system (CNS), clinically manifested by impaired sensory motor function and cognitive impairment. In the pathogenesis of MS, T-cells make the main contribution to the process of inflammatory demyelination; however, the accumulated data on the pathogenesis of MS indicate a significant role of B cells in the progression of the disease. In addition to differentiation into plasma cells that produce autoantibodies, B lymphocytes stimulate T cell activity through antigen presentation, production of proinflammatory cytokines that trigger demyelination and differentiation into memory B cells that promote CD4 + T cell autoproliferation. The presence of "oligoclonal bands" in cerebrospinal fluid and demyelination plaques of brain tissue in MS patients is the result of persistent intrathecal clonal expansion of various B cell populations that contribute to the production of autoreactive antibodies. Thus, B cells located in the central nervous system, protected by the blood-brain barrier (BBB) and, as a consequence, not undergoing complete eradication due to limited penetration of the BBB by immunosuppressive drugs, are a potential target for the treatment of patients with MS. Depletion of B cells through the use of monoclonal antibodies to the CD20 antigen, which is expressed predominantly on mature B lymphocytes, is a promising direction in the therapy of autoimmune diseases. The most readily available anti-CD20 monoclonal antibody is rituximab. The available data from numerous studies on the use of intravenous rituximab have demonstrated a decrease in MR activity and clinical activity in patients with RRMS. At the same time, rituximab does not affect clinical outcomes in patients with PPMS and SPMS with a long history of the disease, probably due to insufficient antibody concentration in intact BBB in the CNS tissue affected by tertiary lymphoid follicles, because the ratio of rituximab concentration in CSF and serum after intravenous infusion ranges from 0.1% to 1-1.7%. Thus, to ensure a sufficient therapeutic concentration of rituximab in the tissues of the central nervous system, the use of the intrathecal route of drug administration is justified. To date, sufficient data have been accumulated on the safety of using intrathecal rituximab in the treatment of both oncological and autoimmune diseases (including MS). Thus, the use of an anti-CD20 monoclonal antibody injected intrathecally in order to achieve adequate B-lymphodepletion in the barrier tissues can increase the duration of the recurrence-free course of autoimmune diseases, suspend their progression, and also prevent clinical relapse when memory B cells are detected.

Arms

Experimental: AHSCT + intrathecal Rituximab

AHSCT with reduced intensity condition regimen (RIC). Lumbar puncture with intrathecal injection of 25 mg Rituximab will be performed once from about D+12 to D+14 AHSCT, depending on the duration of cytopenia.

Interventions

Drug: - Rituximab

All patients receive AHSCT with RIC (Cyclophosphamide, Antithymocyte globulin/Rituximab). After resolution of cytopenia (approximately from about D+12 to D+14 AHSCT), patients will receive intrathecal Rituximab.