...and this one:
Immunoablation with high-dose cyclophosphamide for refractory multiple sclerosis
S. Tilwalli1; R. Balabanov1; D. Stefoski1; G. Katsamakis1; M. Ko1; J. Shammo1; S. Gregory1
1. Neurology, Rush University Medical Center, Chicago, IL, USA.
High-dose cyclophosphamide (HD-CTX) has demonstrated efficacy in arresting multiple sclerosis (MS) and other autoimmune diseases. The aldehyde dehydrogenase mediated resistance of CD34+ cells to CTX allows for immune reconstitution without hematopoietic stem cell rescue.
To assess safety and efficacy of HD-CTX for patients with refractory MS, defined as having failed standard therapies.
We evaluated patients with recurring relapses, worsening disabilities, and increasing magnetic resonance imaging (MRI) lesions over 12 months for immunoablation with HD-CTX (200 mg/kg over 4 days), followed by filgrastim for reconstitution. Clinical, laboratory and MRI monitoring was scheduled at 3-6 month intervals over 24 months.
Six patients were treated since 2005 without lasting complications and monitored over 24 to 36 months. All adverse events resolved using standard therapies within 2 weeks of HD-CTX, and included neutropenic fevers (5 patients), diarrhea (3), hematuria (2), acute dystonia from prochlorperazine (1), urinary tract infection (1), fungal rash (1), and anemia and thrombocytopenia (4). Full hematologic recoveries occurred within 4 weeks of HD-CTX. All 6 patients demonstrated clinical and MRI evidence of improvement with effects ranging from stabilization to dramatic attenuations of disabilities, up to 4.5 Expanded Disability Status Scale points in 5 patients, and 1 to 14 SDs on Multiple Sclerosis Functional Composite in 3 patients. After 20 months of stability 2 patients had a milder than pre-HD-CTX relapse; one by MRI only, and the other clinically and by MRI. The latter patient received intravenous corticosteroids.
Immunoablation with HD-CTX in our patients with intractable MS had realistic safety and tolerability, and resulted in significant improvements ranging from amelioration to stabilization of the disease course, and reduction of disabilities.