Granulocytapheresis as a Possible Cancer Treatment

Abstract

Guest Editor's Introduction: The granulocyte removal column was developed by Japan Immunoresearch Laboratories Co. based upon the hypothesis that the normalization of granulocyte‐to‐lymphocyte ratio would be beneficial for the treatment of cancer since the ratio is increased due to the cancer leukocytosis. The column consists of cellulose acetate beads with a diameter of 2 mm, which removes granulocytes and monocytes from blood with no significant changes in the number of lymphocytes or platelets. The clinical results for cancer treatment was less impressive than the animal experiments. Subsequently, however, the G‐1 Column was found very useful for the treatment of inflammatory bowel disease and rhumatoid arthritis. This paper describes the clinical application for cancer treatment, and was printed in Anticancer Research, vol. 15, page 985–990 (1995). This paper was reprinted here with permission. We assessed the effect of granulocyte apheresis in patients exhibiting increased granulocyte‐to‐lymphocyte ratio in order to overcome granulocytosis occurring in the terminal stages of malignancies. 17 patients with post‐operative recurrent metastatic tumors including 6 gastric, 3 colonic, 2 rectal, 1 esophageal and 5 breast cancers were selected. The granulocytapheresis was performed by extracorporeal vein‐to‐vein circulation equipped with an apheresis column filled with cellulose acetate beads. Each week the patients underwent one or two sessions of treatment that lasted 30 to 50 minutes per session at a flow rate of 30 to 50 ml/min. 15 sessions formed 1 therapeutic cycle. The effect of granulocytapheresis resulted in partial response (PR) in 4 cases, no change (NC) in 7 cases and partial disease (PD) in 6 cases. The performance status showed 30% remission. None of the patients exhibited significant side effects. Since the treatment demonstrated anti‐tumor effects, granulocytapheresis may be applied during combined cancer treatments.

The granulocyte/lymphocyte ratio as an independent predictor of tumour growth, metastasis and progression: Its clinical applications

“…The number of granulocytes showed an upward trend over time after implantation in both the 1x10 6 (P<0.0001) and 1x10 5 (P=0.035) cell groups. In the 1x10 6 cell groups, the number of granulocytes measured on days 11, 14 and 17 after implantation (groups F-H) was significantly increased in comparison with the control group (normal mice, 0.309±0.089), while the number of lymphocytes peaked on day 11 after implantation, then decreased. In the 1x10 5 cell groups, the number of granulocytes on days 11, 14 and 17 after implantation (groups A-C) showed no significant increase in comparison with the control group.…”

“…Several investigators have suggested that the G/L ratio is a good indicator for the evaluation of the condition of a tumour-bearing host (4,6), although the correlation between granulocytes and lymphocytes or between the G/L ratio and clinicopathologic factors is unclear (8).…”

The mode of actions of the Adacolumn therapeutic leucocytapheresis in patients with inflammatory bowel disease: a concise review

“…It was thought that lymphocytes were depleted by activated myeloid leucocytes. The Adacolumn was developed to take away the excess and activated myeloid cells, hoping that this might lead to enhanced lymphocyte function [26,76,77]. Figure 8 summarizes the actions which ideally should be expected from therapeutic GMA in patients with IBD and other immune-related complications.…”

Selectively Induced Apoptosis in Human Neutrophils in the Presence of Oxidative Phenoxazines, 2-Amino-4,4α-dihydryo-4α-7H-phenoxazine-3-one and 2-Aminophenoxazine-3-one, Preceded by Decrease of Intracellular pH, Depolarization of the Mitochondria, and Inhibition of Superoxide Generation

“…In addition to the above, Tabuchi et al (46,47) reported that when neutrophils were removed from circulating blood of rabbits with tumors or patients with recurrent metastatic tumors by apheresis, the cancers were extensively undersized, suggesting that neutrophils are relevant to the development of cancer. Currently, neutrophils are recognized as the cells to modify tumor growth, angiogenesis, and metastasis (48).…”