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Promise and Progress - The Aplastic Anemia Controversy

Sidney Kimmel Gives Hopkins Its Biggest Gift Ever

The Aplastic Anemia Controversy

Date: December 1, 2002

What is the best therapy for the rare but deadly blood disorder known as aplastic anemia? It depends on whom you ask. Most physicians believe it is bone marrow transplant, a treatment that destroys diseased blood and bone marrow and replaces it with an infusion of healthy marrow from a donor. And for the 20 percent of patients who are fortunate enough to be young and have a brother or sister whose immune system matches theirs, most everyone would agree. The choice is not so clear for the remaining 80 percent of aplastic anemia patients beyond their mid to late twenties. In this group, even when the patient has a matching donor, bone marrow transplant does not work well, with failures exceeding 40 percent.

For these patients, many physicians recommend treatment with immunosuppressive drugs. Since aplastic anemia is an autoimmune disorder resulting from the immune system’s attack on blood stem cells, drugs that suppress the immune system do work for many patients. However, remissions are often short lived, and the therapy can lead to other bone marrow disorders and even leukemia.

At Johns Hopkins, however, there was speculation that another treatment might be worth exploring. When Robert Brodsky, M.D., came to the Cancer Center in 1996, Bone Marrow Transplant Director Richard Jones, M.D., shared with him some files left behind by a former professor and leading aplastic anemia expert Lyle Sensenbrenner, M.D. The files contained data from two decade-old studies showing aplastic anemia could be successfully treated with the single cancer drug cyclophosphamide.

Intrigued, Brodsky began his own trials to confirm the dated findings. After studying the therapy in 19 patients, Brodsky has just published results showing the therapy to be as good, if not better, than immunosuppressive therapy for this group of patients. After an average follow-up of more than two years, 14 of the patients treated in his study are disease free and have not required any additional therapy. That’s a 75 percent success rate for a rapidly fatal disease where 80 percent of untreated patients die within two years.

How does it work? Well, Brodsky says it’s like rebooting a computer. The cyclophosphamide wipes out all of the old information contained in the immune system, and as new immune cells are formed, the slate is wiped clean, and the new cells function normally.

Despite the success of these studies, Brodsky finds that many hematologists and oncologists are hesitant to try it. “Even with their shortfalls among older patients, bone marrow transplant and immunosuppressive therapy both have proven track records, so many physicians are hesitant to try the new therapy as a front line treatment,” he says. Admittedly the cyclophosphamide therapy is not perfect. Patients treated with the drug alone typically take about 20 days longer to recover normal blood counts than bone marrow transplant patients. Still, in his studies, this delay does not appear to have any affect on remission rates.

 So for Brodsky and his colleagues, the evidence to date is quite clear. In older patients who do not have matching marrow donors, and potentially even for those that do, cyclophosphamide therapy offers the best chance for a sustained treatment-free remission, he says. He continues to study the new therapy, and hopes mounting evidence of its effectiveness will persuade the critics