Fluctuations in Peripheral Blood Leukocyte and Platelet Counts and Leukocyte Recruitment With Large Volume Leukocytapheresis in Healthy Volunteers

Abstract

Based on sporadic reports indicating that the effectiveness of leukocytapheresis (LCAP) is proportional to the number of leukocytes removed, it is anticipated that increasing the volume of blood treated, and thus the number of leukocytes removed, will improve the effectiveness of therapy. In advance of its clinical application, the possible clinical usefulness of large volumes of LCAP (pulse LCAP), which treats 5000 mL of blood rather than the usual volume of 3000 mL, was investigated in healthy subjects. As compared with conventional LCAP, pulse LCAP provided comparable safety and enabled the removal of approximately 4.7 times more neutrophils, 1.2 times more lymphocytes, and 1.6 times more monocytes. It also resulted in a more pronounced overshoot phenomenon, as well as lymphocyte and monocyte overshoot, which are not seen with conventional LCAP. The neutrophil overshoot resulted from the recruitment of leukocytes from the bone marrow neutrophil pool as well as from the circulating neutrophil pool and marginal neutrophil pool. Recruitment from the bone marrow pool involved not only recruitment of mature neutrophils but also recruitment from all stages of differentiation and proliferation, including the pluripotent stem cell (CFU-GEMM) fraction; granulocyte-monocyte precursor cell (CFU-GM) fraction; and the fraction of juvenile granulocyte precursors cells capable of cell division, from myeloblasts to myelocytes. Based on the lymphocyte and monocyte overshoot, it was inferred that cells were recruited from mucosal lymphatic tissue, in addition to the lymph nodes, spleen, thymus, and bone marrow. These phenomena might play an important role in the mechanism that underlies the effectiveness of LCAP and the increased effectiveness of pulse LCAP, and it will be necessary to work to elucidate them. Moreover, it appears that investigating the clinical efficacy of pulse LCAP in patients who do not respond to conventional LCAP would be of major significance.