Treatment of cancer chemotherapy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome by protein A immunoadsorption of plasma
Article first published online: 28 JUN 2006
Copyright © 1993 American Cancer Society
Volume 71, Issue 5, pages 1882–1892, 1 March 1993
How to Cite
Snyder, H. W., Mittelman, A., Oral, A., Messerschmidt, G. L., Henry, D. H., Korec, S., Bertram, J. H., Guthrie, T. H., Ciavarella, D., Wuest, D., Perkins, W., Balint, J. P., Cochran, S. K., Peugeot, R. L. and Jones, F. R. (1993), Treatment of cancer chemotherapy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome by protein A immunoadsorption of plasma. Cancer, 71: 1882–1892. doi: 10.1002/1097-0142(19930301)71:5<1882::AID-CNCR2820710527>3.0.CO;2-E
- Issue published online: 28 JUN 2006
- Article first published online: 28 JUN 2006
- Manuscript Accepted: 10 SEP 1992
- protein A;
- staphylococcal protein A;
- PROSORBA column;
- chemotherapy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome;
- thrombotic thrombocytopenic purpura (TTP);
- hemolytic uremic syndrome (HUS);
- circulating immune complexes (CIC);
- extracorporeal therapy
Background. Chemotherapy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (C-TTP/HUS) is a condition involving thrombocytopenia, microangiopathic hemolytic anemia, and progressive renal dysfunction that develops in 2–10% of patients with a history of malignant neoplasms treated with certain chemotherapeutic agents. Pathogenesis of the disease may depend on the following: (1) generation of endothelial lesions in the kidney microvasculature, resulting from drug toxic effects and/or generation of small soluble circulating immune complexes (CIC), and (2) generation of autoantibodies and/or CIC that trigger aggregation and deposition of platelets around the lesions.
Methods. Extracorporeal immunoadsorption treatment of plasma (PROSORBA columns, IMRÉ Corporation, Seattle, WA) to remove immunoglobulin G and CIC was evaluated in 55 patients for the potential to induce significant clinical benefits (increase in platelet count, decrease in hemolysis, stabilization of renal function) and longer survival.
Results. Response to therapy was achieved in 25 of 55 patients examined. Response was associated with an estimated 1-year survival rate of 61%, as compared with an estimated survival rate of only 22% in those who did not respond (P = 0.0001). Patients whose malignant neoplasms were in complete or partial remission at the time of development of C-TTP/HUS had a significantly higher estimated 1-year survival rate (74%) as compared with a historic control group of patients receiving other treatments (22%, P = 0.0161). Clinical responses were correlated with normalization of serum levels of CIC and complement components C3c and C4. There were no side effects associated with 75% of treatments. Immunoadsorption therapy was associated with generally mild to moderate manageable side effects, such as fever, chills, nausea/vomiting, respiratory symptoms, pain, hypertension, and hypotension, which were reported in 25% of procedures.
Conclusions. This multicenter study establishes protein A immunoadsorption as an effective and safe treatment for cancer chemotherapy-associated TTP/HUS, an otherwise fatal disease.