CD34+ selected autologous peripheral blood stem cell transplantation for multiple sclerosis: report of toxicity and treatment results at one year of follow-up in 15 patients.
OBJECTIVE
Autologous stem cell transplantation (ASCT) is currently being evaluated as a therapy for patients with multiple sclerosis (MS). We report the results of a phase II trial to evaluate feasibility and toxicity of CD34+ selected ASCT (CD34+/ASCT) and treatment results at one year of follow-up.


METHODS
Patients with advanced secondary progressive (SP) or relapsing-remitting (RR) MS and confirmed worsening of the extended disability status scale (EDSS) in the previous year despite interferon or other immunotherapies were included. Peripheral blood stem cells were obtained by leukaphereses after mobilization with cyclophosphamide (Cy) and granulocyte colony-stimulating factor (G-CSF). CD34+ selection was performed by means of an Isolex 300 or CliniMACS device. BCNU, Cy and antithymocyte globulin (ATG) were administered as conditioning regimen.


RESULTS
Fifteen patients (9 SPMS and 6 RRMS) with a median EDSS of 6.0 (4.5-6.5) and a median of 3 (1-7) relapses in the previous year were included. Mobilization was unsuccessful in one patient. During mobilization, one patient had a transient neurologic deterioration. The main complication during ASCT were engraftment syndrome, which developed in three patients, CMV reactivation in one, and neurologic deterioration in two patients coinciding with high-fever related to ATG. Hematologic recovery was fast and complete in all cases. At 12 months, the EDSS had improved in three patients, worsened in two and remained stable in nine. Despite withdrawal of all immunosuppressive therapy only two patients had relapses. Magnetic resonance imaging showed disappearance of enhanced T1 lesions but oligoclonal bands persisted in the cerebrospinal fluid of all evaluated cases.


CONCLUSIONS
CD34+/ASCT using BCNU, Cy and ATG as conditioning regimen has an acceptable toxicity and clearly reduces the progression of MS. Further follow-up is necessary to establish the real impact of this procedure on the long-term evolution of the disease.
Carreras
Enric
E
BMT Unit, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain. carreras@clinic.ub.es
Saiz
Albert
A
Marín
Pedro
P
Martínez
Carmen
C
Rovira
Montserrat
M
Villamor
Neus
N
Aymerich
Marta
M
Lozano
Miquel
M
Fernández-Avilés
Francesc
F
Urbano-Izpizua
Alvaro
A
Montserrat
Emili
E
Graus
Francesc
F
D000328:Adult; D018952:Antigens, CD34; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007107:Immune System / Q000166:cytology; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D012008:Recurrence; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D018952:Antigens, CD34