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.

Extracorporeal immunoadsorption of plasma to remove IgG and circulating immune complexes (CIC) was evaluated as a therapy for adults with treatment-resistant immune thrombocytopenic purpura (ITP). Seventy-two patients with initial platelet counts less than 50,000/microL who had failed at least two other therapies were studied. They received an average of six treatments of 0.25 to 2.0 L plasma per procedure over a 2- to 3-week period using columns of staphylococcal protein A-silica (PROSORBA immunoadsorption treatment columns; IMRE Corp, Seattle, WA). The treatments caused an acute increase in the platelet count to greater than 100,000/microL in 18 patients and to 50,000 to 100,000/microL in 15 patients. The median time to response was 2 weeks. Responses were transient (less than 1 month duration) in seven of those patients (10%), but no additional relapses were reported over a follow- up period of up to 26 months (mean of 8 months). Clinical responses were associated with significant decreases in specific serum platelet autoantibodies (including anti-glycoprotein IIb/IIIa), platelet- associated Ig, and CIC. Thirty percent of treatments were associated with transient mild to moderate side effects usually presenting as a hypersensitivity-type reaction. Continued administration of failed therapies for ITP, which always included low-dose corticosteroids (less than or equal to 30 mg/d), had no demonstrable influence on the effectiveness of immunoadsorption treatment but did depress the incidence and severity of side effects. The degree of effectiveness of protein A immunoadsorption therapy in patients with treatment-resistant ITP is promising and further controlled studies in this patient population are warranted.

No abstract

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by the presence of antiplatelet antibody which sensitizes platelets resulting in their clearance by the reticuloendothelial system. Extracorporeal protein A immunoadsorption has been demonstrated to be of benefit in the treatment of this autoimmune disorder. In the present study, a patient with underlying systemic lupus erythematosus (SLE) presented with ITP. The patient received 14 immunoadsorption treatments and responded to therapy. During the course of immunoadsorption treatments, there was a decline in circulating immune complex (CIC) levels, antinuclear antibody (ANA) levels, and antiplatelet IgG antibody levels. In addition, elevated levels of antiidiotypic IgG antibody detected before initiation of therapy were significantly reduced during the course of immunoadsorption treatments. This study suggests that specific autoimmune idiotypic IgG antibody and corresponding antiidiotypic IgG antibody responses may be modulated in association with extracorporeal immunoadsorption employing protein A/silica columns.

In the present case study, a patient with Non-Hodgkin. Lymphoma underwent combination chemotherapy resulting in severe pancytopenia requiring transfusion support with blood products. The patient became refractory to random donor platelet transfusions and subsequently received five immunoadsorption treatments. The patient's clinical response to immunoadsorption therapy was assessed by monitoring platelet transfusion recovery and survival. In addition, changes in antibody responses were assessed. Early during the course of immunoadsorption therapy, antiplatelet immunoglobulin G (IgG) alloantibody was detected. There was a decline in antiplatelet IgG alloantibody levels by the last immunoadsorption treatment associated with increases to platelet correct count increments after completion of immunoadsorption therapy. In addition, elevated levels of antiidiotypic IgG antibody detected early during the course of therapy were significantly reduced by the last immunoadsorption treatment. This case study suggests that specific alloimmune idiotypic IgG antibody and corresponding antiidiotypic IgG antibody responses may be modulated in association with extracorporeal immunoadsorption employing protein A/silica columns.