Intense T cell depletion followed by autologous bone marrow transplantation for severe multiple sclerosis.
BACKGROUND
Certain stem cell transplantation procedures might slow down inflammatory pathology in multiple sclerosis (MS).


OBJECTIVE
To halt disease progression in aggressive MS by a bone marrow transplantation (BMT) protocol aimed at maximum T cell suppression.


METHODS
Autologous BMT was performed in 14 patients with rapid secondary progressive MS (median EDSS score at baseline, 6; median disease duration, five years). To accomplish rigorous T cell ablation, a strong conditioning protocol was chosen--cyclophosphamide, total body irradiation, and antithymocyte globulin. To minimise the possibility of reinfusing mature T cells in the graft, bone marrow, not peripheral blood, was used as the CD34+ stem cell source.


RESULTS
Median follow up was 36 months (range, 7-36). Post-transplant haemopoietic recovery was successful in all patients. Early toxicity included Epstein-Barr virus related post-transplantation lymphoproliferative disorder. Longterm effects were development of antithyroid antibodies (three) and myelodysplastic syndrome (one). One patient died of progressive disease five years after transplantation. Treatment failure, defined by EDSS increase sustained for six months or more, was seen in nine patients and stabilisation or improvement in five. Other clinical parameters generally showed the same outcome. No gadolinium enhanced lesions were seen on post-treatment magnetic resonance imaging, in either cerebral or spinal cord scans. However, cerebrospinal fluid oligoclonal bands remained positive in most cases.


CONCLUSIONS
This strong immunosuppressive regimen did not prevent clinical progression in patients with aggressive secondary MS. The lack of efficacy, together with some serious side effects, does not favour the use of similar rigorous T cell depleting protocols in the future.
Samijn
J P A
JP
Department of Neurology, MS Centre ErasErasmus MC, Postbox 2040, 3000 CA Rotterdam, The Netherlands.
te Boekhorst
P A W
PA
Mondria
T
T
van Doorn
P A
PA
Flach
H Z
HZ
van der Meché
F G A
FG
Cornelissen
J
J
Hop
W C
WC
Löwenberg
B
B
Hintzen
R Q
RQ
D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000378:metabolism* / Q000528:radiation effects*; D014182:Transplantation, Autologous
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide