Treatment of cancer chemotherapy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome by protein A immunoadsorption of plasma.

Overview

abstract

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, IMRE 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.