Friday, March 23, 2007

High dose cytoxan for multiple sclerosis

Gladstone DE et al. High dose cyclophosphamide for moderate to severe refractory multiple sclerosis. Arch Neurol 2006; 63:1388-1393.

The authors studied refractory MS, defined as EDSS scores of 3.5 or higher after 2 or more FDA approved DMD's. 12 patients received 200 mg/kg over four days. No patients increased EDSS by more than one point. Five decreased by one or more points. Patients reported improvement in ll QOL measures.

Goal of therapy is to stop disease progression.
Procedure was 200 mg/kg based on IBW over f days. Hemorrhagic cystitis prevention was done with mesna and forced diruresis. Antibacterial, antiviral and antifungal prophylaxis was given. Evaluation included EDSS, neuro-opthalmologic evaluation and MRI and QOL eval using short form 36.

Patients suffered absolute neutropenia for nine days, received a median of i unit prbc's

Alternatives: mitoxantrone, stem cell mobilization (filgastrim)

1 comment:

Neurodoc said...

The study of 13 patients included 7 with spms, and 12 evaluable patients. 5/12 had sustained effects > 15 months with a decrease of > 1.0 on EDSS. Bladder dysfunction improved in 75 %, in QOl scores.

The use of HDC is novel with a single 4 day infusion at "ultra-high" doses but assessment is marred by mixed population, short followup (6-24 mo) confounding prior therapies including MTX. No account was made for rrms patients who would be expect to have lower EDS after finishing a relapse. No effect was seen on MRI. Six patients had febrile neutropenia and needed transfusions and filgrastim. Hat tip to Hillel Panitch for comments on study.