Patient-Reported-Outcomes and Safety of Autologous Stem Cell Transplantation in Multiple Sclerosis: A Single Center Experience with the "Mexican Method" in 1300 Persons

BACKGROUND Multiple sclerosis (MS) is a central nervous system autoimmune, inflammatory, demyelinating, and neurodegenerative disease that significantly lowers the quality of life for those affected. Autologous hematopoietic cell transplantation (aHSCT) has been demonstrated to be superior to new immunomodulatory drugs and is currently a proven therapeutic strategy, the patient reported outcomes (PROs) assessing the expanded-disability status scale (EDSS) improving in around 80%. We have previously reported that autotransplants for several hematologic malignancies can be done in the outpatient setting using refrigerated non frozen peripheral blood stem cells. We now report data from persons with MS receiving autotransplants in an outpatient setting using refrigerated blood cells followed for up to 24 months after aHSCT.

MATERIALS AND METHODS Since June 2015, 1,300 consecutive patients with MS have been autografted in the Centro de Hematología y Medicina Interna de Puebla, México using non-frozen peripheral blood stem cells. All the aHSCT were started as outpatients, employing the "Mexican method": Cyclophosphamide 200 mg/kg and rituximab 1,000 mg; protocol is registered in ClinicalTrials.gov identifier NCT02674217. Eligibility criteria included all the following: Karnofsky performance score >70%, EDSS ≤8 in the 2 weeks pretransplant, CNS magnetic resonance image (MRI) ≤3 mo pretransplant, normal heart, liver, lung, and kidney function, ≥6 mo since exposure to immune suppressive drugs. The primary outcome measure was the PRO (EDSS changes) and secondary outcomes were overall survival (OS) and progression-free survival (PFS). Disability progression was defined as patients with EDSS ≤5.5 who experienced a PRO-EDSS increase of ≥1.0, whereas for patients with EDSS >5.5, progression was a PRO-EDSS increase of ≥0.5.

RESULTS A total of 1300 persons were prospectively included (871 females and 429 males); median age was 47 years. 637 patients presented with relapsing remitting MS (RRMS), 390 with secondary progressive (SPMS) and 273 with primary progressive (PPMS). All procedures were started on an outpatient basis; 45 persons (3.5%) needed to be admitted to the hospital during the procedure as a result of neutropenic fever (20), pneumothorax (4), nausea and/or vomiting (4) or other complications; there were two fatalities (0.1%). One to three apheresis (median 1) were needed to obtain at least 1x10⁶/Kg viable CD34 cells. Patients recovered above 0.5 x10⁹/L absolute granulocytes on day 8 (median, range 2-13), whereas platelet recovery above 20 x10⁹/L on day 4 (median, range 0-10). Patients remained in our premises for 28 days and PROs were surveyed by phone / zoom every 3 months after aHSCT. PROs could be recorded in 382/1300 persons (29%): PRO-response rate (no disability progression) at 12 months was 80% for all the patients,( 81.4% for RRMS, 76.2% for PPMS and 80% for SPMS). At 24 months the response rate was 85.8% for RRMS, 77.3% for PPMS and. 70% for SPMS. Changes in the EDSS score were statistically better at 12 (p<0.0001), 18 (p=0.0017) and 24 months (p=0.0003).

CONCLUSIONS aHSCT for persons with MS employing the "Mexican method" is very safe and related with a positive PRO response rate (around 80% for all patients) at 12 and 24 months; results are better than those informed employing immunosuppressive drugs.

No relevant conflicts of interest to declare.