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More MS news articles for January 2003

Myasthenia Gravis Responds to High-Dose Cyclophosphamide Immune "Rebooting"

Jan 27, 2003
By Karla Gale
Reuters Health
New York

Three patients with myasthenia gravis (MG) refractory to conventional treatments have been successfully treated with high-dose cyclophosphamide at Johns Hopkins and remain relapse-free after 7 to 40 months of follow-up.

Furthermore, Dr. Robert A. Brodsky and associates report in the Annals of Neurology for January, 75 patients have been successfully treated at their institution with high-dose cyclophosphamide--an approach they call immune system "rebooting"--for aplastic anemia, lupus erythematosus, pemphigus and autoimmune neuropathies (see Reuters health report, January 16, 2003). Only one death ensued, which was attributed to uncontrollable fungal encephalitis.

"We're cautious not to use the term 'cure'," Dr. Brodsky told Reuters Health, "although some patients with aplastic anemia are beyond 10 years [after high-dose cyclophosphamide treatment], and even in lupus, some are beyond 5 years. To see complete remission is unprecedented."

In their paper, the researchers explain that ablation of the immune system and restoration with bone marrow transplantation has been successful in treating some autoimmune diseases, but this approach entails risks. High-dose cyclophosphamide, they note, has been shown to eliminate the mature immune system, after which hematopoietic stem cells proliferate to reconstitute the immune system, without the need for bone marrow transplantation.

The three MG patients reported in the current study had previously failed treatment with thymectomy, plasmapheresis and agents that included pyridostigmine, prednisone, azathioprine, cyclosporine and mycophenolate.

"These were very carefully selected patients resistant to everything, and with life-threatening disease," Dr. Brodsky pointed out.

His group administered cyclophosphamide 50 mg/kg/day for 4 days, followed by granulocyte colony stimulating factor initiated on day 6 after the last dose. Prophylactic antibiotics were also administered.

They describe the patients' responses as "dramatic," beginning approximately 2 months after treatment. One of the three patients had a "mild temporary setback," but has since returned to work full time. At the time of publication, the patients were during well after 7 to 40 months follow-up. Immunosuppressive medications have been reduced to minimal levels, the report indicates.

In an accompanying editorial, Dr. Richard A. Lewis and Robert P. Lisak, of Wayne State University School of Medicine in Detroit write, "Although the results described are exciting and generate enthusiasm, we would urge clinicians who treat patients with...autoimmune/immunopathologically mediated diseases of the nervous system to...await the results of further investigations...before adapting this therapy, even for patients with significant disability and/or side effects from their current therapy."

Dr. Brodsky agrees with the two editorialists, up to a point.

"For neurologists and rheumatologists, dealing with this type of drop in white blood cell counts is new, and it shouldn't be taken lightly. We don't want everyone in the community to start doing this until we have further proof."

However, he believes that "high dose toxicity can be managed by...any major university or community hospital" that routinely uses high-dose cyclophosphamide for cancer patients.

He also expects that, in time, high-dose cyclophosphamide may even replace treatment with monoclonal antibodies to TNF and other cytokines. The problem is, he said, that there is not just one individual cytokine involved in autoimmune diseases. "Most patients have a moderate to good response to agents like infliximab, but the response is not durable," he explained.

Ann Neurol 2003;53:29-34.

© 2003 Reuters Ltd

High-Dose Cyclophosphamide Benefits Patients With Refractory SLE

Jan 16, 2003
Reuters Health
New York

High-dose cyclophosphamide does not require stem cell transplantation to benefit patients with systemic lupus erythematosus that is refractory to conventional treatment, physicians at Johns Hopkins University School of Medicine report in the January 10th issue of Arthritis and Rheumatism.

High-dose chemotherapy combined with hematopoietic stem cell transplantation has been used successfully in treating lupus and other severe autoimmune disorders. However, this approach is accompanied by the concern that autografting may lead to reestablished autoimmunity. In contrast, cyclophosphamide induces maximal immunosuppression without myeloablation.

Dr. Michelle Petri and her colleagues in Baltimore used this approach to treat 14 patients with moderate to severe SLE that failed to respond to corticosteroids and at least one other immunosuppressive agent.

Five patients had diffuse proliferative glomerulonephritis, four had membranous glomerulonephritis, two had encephalopathy, one had cerebellar ataxia. One had extensive skin involvement, while another was affected by severe pyoderma gangrenosum.

Cyclophosphamide 50 mg/kg was administered for 4 consecutive days. Patients were then treated with granulocyte colony-stimulating factor to stimulate neutrophil reconstitution.

Five patients achieved a complete response lasting throughout a median follow-up period of 32 months. The six patients who exhibited partial response were subsequently effectively treated with agents that, prior to high-dose cyclophosphamide, were ineffective. Two patients with renal disease failed to respond, and one with CNS involvement later developed renal disease.

All patients survived the procedure without developing fungal infections, premature ovarian failure, or mucositis grade >1.

"The idea with this treatment is to blast the lupus once and wipe out the abnormal immune system and allow the body to relearn and function normally without further therapy," Dr. Petri explained in a press statement.

Arthritis Rheum 2003;48:166-167.

© 2003 Reuters Ltd