Background: With the goal of immune system reset, autologous hematopoietic stem cell transplantations have been done in patients with multiple sclerosis (MS).
Material and methods: 131 consecutive patients with MS were autografted in a single center using non-frozen peripheral blood stem cells (PBSC) on an outpatient basis and conditioning with cyclophosphamide (Cy) and rituximab. The protocol was registered in ClinicalTrials.gov identifier NCT02674217. The PBSC mobilization schedule was done with Cy and filgrastim (G-CSF). Intravenous Cy (50 mg/Kg) was delivered on days - 11 and - 10. Subcutaneous G-CSF (10 ug / Kg / bid) was delivered on days - 9 to - 1.. The apheresis procedure was performed on day - 2. The apheresis objective was to reach at least 1 x 106 viable CD34+ cells/Kg. As outpatients and after collecting the PBSC, intravenous Cy (50 mg / Kg) was delivered along a 120 minute period, on days - 2 and - 1 followed by MESNA (1000 mg/m2 along a 180-minute period). After the intravenous Cy, oral ondansetron), oral cotrimoxazole, oral fluconazole and oral acyclovir were used in all patients until granulocytes were greater than 0.5 x 109/L. After the recovery of the granulocytes, patients were given rituximab (375 mg/m2 along a 3 h period) and subsequently rituximab (100 mg) every two months along a 12-month period. The cumulative dose of Cy is 200 mg/Kg.
Results: 80 females and 51 males were included; median age was 47 years. All procedures were started on an outpatient basis and two persons were admitted to the hospital during the procedure. In order to obtain at least 1 x106 / Kg viable CD34 cells, one to four apheresis were performed (median 1). Total number of viable CD34+ cells infused ranged between 1 and 9.6 x106 / Kg (median 2.2). Patients recovered above 0.5 x109/L absolute granulocytes on median day 9 (range 6 to 12). Two individuals needed red blood cells but none needed platelet transfusions. There were no transplant related deaths, the 120-month overall survival being 100%. In a subset of 25 persons followed for 5 months or more the EDSS was assessed three months after the graft and means diminished from 5.4 to 4.9. The EDSS score improved in 11 patients (44%), remained stable in 7 (28%) and worsened in 7 (28%). A tendency to diminish the EDSS score as a function of time after the autograft was observed in this subset of individuals.
Conclusions: It is possible to conduct autotrasplants for patients with MS employing non-frozen peripheral blood stem cells and outpatient conduction. Additional information is needed to assess the efficacy of these procedures in the treatment of patients with MS.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.