Elimination of anemia-inducing substance by cyclic plasma perfusion of tumor-bearing rabbits

We carried out a fundamental study to search for a therapeutic modality that would remove the anemia-inducing substance (AIS) from the plasma of cancer patients because it is thought to be one of the substances responsible for anemia and immunodeficiency in advanced cancer patients. Using AIS isolated from the plasma of patients with advanced ovarian carcinoma, we confirmed that adsorption of AIS to noncoated charcoal was nonspecific and high. Moreover, it was verified that VX2 carcinoma-bearing rabbits are an optimal experimental model for plasma perfusion. The data obtained on day 40 after transplantation (hemoglobin, 9.1+/-2.1 g/dl; osmotic pressure inducing RBC lysis, 137+/-11 mosmol/kg; lymphocyte stimulation index, 8.8+/-8.6; and RBC fragility-inducing activity, 40+/-9 mosmol/kg) proved similar to the hematological findings in patients with cancer cachexia. A 1-h plasma perfusion (3 ml/min) through noncoated charcoal was performed in tumor-bearing rabbits, and it resulted in the restoration of RBC fragility-inducing activity and suppression of lymphocyte blast formation to pretransplantation values. When plasma perfusion was performed every 3 days, RBC fragility-inducing activity, which increased again 3 days after perfusion, was diminished, and RBC osmotic resistance was within the normal range from the fourth perfusion onward. These results showed that cyclic plasma perfusion is effective in sustained removal of RBC fragility-inducing factor from plasma, suggesting that it might have the potential for clinical application.