Cyclophosphamide and other new agents for the treatment of severe aplastic anemia

Tisdale, John F; Dunn, Daniel E; Maciejewski, Jaroslaw

« PreviousSeminars in Hematology
Volume 37, Issue 1 , Pages 102-109, January 2000

Cyclophosphamide and other new agents for the treatment of severe aplastic anemia☆

John F Tisdale
- Address reprint requests to John F. Tisdale, MD, Bldg 10, Room 9N116, Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892.
- From the Molecular and Clinical Hematology Branch, National Insitute of Diabetes and Digestive and Kidney Diseases, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
- From the Division of Hematology, University of Utah, Salt Lake City, UT, USA
Daniel E Dunn
- From the Molecular and Clinical Hematology Branch, National Insitute of Diabetes and Digestive and Kidney Diseases, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
- From the Division of Hematology, University of Utah, Salt Lake City, UT, USA
Jaroslaw Maciejewski
- From the Molecular and Clinical Hematology Branch, National Insitute of Diabetes and Digestive and Kidney Diseases, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
- From the Division of Hematology, University of Utah, Salt Lake City, UT, USA

Abstract

Severe aplastic anemia (SAA) has a poor prognosis in the absence of treatment. Current accepted therapeutic strategies include allogeneic stem-cell transplantation and immunosuppression, both resulting in long-term survival in the majority of patients. Although human leukocyte antigen (HLA)-matched sibling stem-cell transplantation is highly effective, the 25% probability of finding a suitable sibling donor within a family renders this approach available to only a minority of patients. Transplantation using HLA-matched, unrelated donors carries a high risk of treatment failure along with considerable toxicity. While combined immunosuppression with both antithymocyte globulin (ATG) and cyclosporine A (CSA) produces hematologic improvement in most patients, relapse is common. Late evolution of aplastic anemia to other serious hematologic disorders, including paroxysmal nocturnal hemoglobinuria (PNH), myelodysplasia, and acute leukemia, is also a significant problem following treatment with ATG/CSA. Recently, results of immunosuppression in SAA with another potent immunosuppressive agent, Cyclophosphamide, were reported in a small number of patients. The overall response rate was similar to that seen with ATG/CSA, but relapse and late clonal disease were not observed during a long period of follow-up. A larger randomized trial comparing sustained hematologic response rates to either conventional immunosuppression with ATG/CSA or high-dose cyclophosphamide and CSA is now underway; secondary end points include response duration, event-free survival, and overall survival. Additionally, a number of protocols designed to test the efficacy of alternative immunosuppressive or immunomodulatory agents are being developed.

No full text is available. To read the body of this article, please view the PDF online.