Outpatient Hematopoietic Grafting in Patients with Multiple Sclerosis Employing Autologous Non-Cryopreserved Peripheral Blood Stem Cells: A Feasibility Study

Background:

Multiple sclerosis (MS) is a chronic, inflammatory, debilitating disease that causes destruction of central nervous system (CNS) myelin, with varying degrees of axonal damage. With the goalofd re-setting the immune system, autologous hematopoietic stem cell transplantations (HSCT) have been done in patients with MS since 1996 and more than 700 HSCTs have been performed around the world. The risk of transplant related mortality in HSCT for MS has declined over the past years.

Material and methods:

Consecutive patients with MS were autografted in a single center using: Hematopoietic stem cells (HSC) were mobilized with cyclophosphamide (Cy), 3 gr/m2 and G-CSF, the procedure was conducted on outpatient basis employing peripheral blood non-frozen HSC and conditioning with high-dose Cy (100 mg/Kg) and post-transplant G-CSF and rituximab. Antibiotics, antimycotics and antivirals were given orally.

Results:

Thirteen patients with MS were prospectively accrued in the study. There were 7 females and 6 males. Median age was 48 years, range 24 to 65. The expanded disability status scale (EDSS) score of these patients had a median of 5 points (range 1 to 6). All the autografts were started on an outpatient basis and two persons were admitted to the hospital during the procedure (persistent nausea/vomiting and neutropenic fever); they stayed in the hospital for 48 hours. In order to obtain a minimum of 1 x10⁶ viable CD34+ cells/Kg, one to four apheresis were done (median 1). The total number of viable CD34+ cells infused to the patients ranged between 1 and 9.6x10⁶ (median 3.1). Patients recovered above 0.5 x10⁹/L absolute granulocytes on median day 9 (range 6 to 12). No individuals needed transfusions of red blood cells nor platelets transfusions. There were no transplant-related deaths and the 23-month overall survival of the autografted patients is 100%. Median cost of the procedure was 30 000 USD. In 8 persons the EDSS was assessed three months after the graft; it diminished from a median of 4.5 to a median of 2.5. In 5 patients, the three months re-assessment of the EDSS has not been possible as a result of the time elapsed after the autograft.

Discussion:

These data indicate that it is possible to conduct autotrasplants for patients with MS employing a simplification of the conventional procedures by means of non-frozen peripheral blood stem cells and outpatient conduction. Additional information is needed to asses the efficacy of these procedures in the treatment of patients with MS.