High dose cyclophosphamide (HiCY) without stem cell rescue has been shown to induce remissions in people with severe autoimmune disorders (SADS). However, up to 80% of these people ultimately relapse. Here these investigators review the outcomes of seven people treated with two cycles and one person treated with three cycles of HiCY. The diseases re-treated were scleroderma, MS, three people with severe aplastic anemia (SAA), and three people with myasthenia gravis (MG). All but two with SAA had received standard immunomodulatory therapy for their disease up front and had been refractory. All people had complete hematologic recovery. Overall survival in this cohort was 100%. All subjects relapsed after the initial cycle but event free survival thereafter was 93.3%. All are still in remission except two people with MG, one of whom relapsed after a severe GI infection requiring hospitalization, and the other relapsed 3 years after the second treatment and she did not respond to the third treatment. This shows that HiCY can be safely re-administered in people with SAA and refractory SADS. The quality and duration of second remissions appears to be equal or superior to the first remission.
“High-dose cyclophosphamide, short of immunoablative autologous bone marrow transplantation, is one of the most powerful immune system rebooters used in MS. It is associated with serious bone marrow suppression and MSers treated in this way are at high risk of infections and bleeding. Most MSers need to spend several weeks in or close to a hospital to have bone marrow support. In addition, it causes severe hair loss, which is transient, mucositis (sloughing and ulceration of the lining of mouth) and most woman who have this treatment develop ovarian failure (premature menopause). Once we have the option of using alemtuzumab I doubt anybody will take the acute or short-term risks of cyclophosphamide treatment. Would you?”
“The late John Newsom-Davis, the Professor of Neurology at Oxford, used to query the need for using various sledgehammers to treat autoimmunity. I am beginning to think he was right. We need a more targeted approach. Maybe the Charcot Project will surprise us.”