[Increased apoptosis of peripheral blood leukocytes correlates with leukopenia after high-dose chemotherapy]

Time-related changes in apoptotic leukocyte numbers were studied in peripheral blood sampled from 12 cancer patients before and after myeloablative chemotherapy (MC); six of them received hemopoietic cell grafts. Apoptotic leukocytes were counted in fresh and ex vivo incubated blood samples. Nuclear chromatin autolysis was registered in supravital Acridin Orange-stained granulocytes and lymphocytes. The levels of apoptosis in fresh peripheral blood were under 1.5%. Incubation for another 3 h revealed considerable numbers of apoptosis-prone leukocytes both in untreated patients and healthy donors. High-dose chemotherapy with busulphan, cyclophosphamide or alkeran was followed by a sharp increase in apoptotic cell counts which peaked on days 7-9, before leukopenia started on days 13-15 at the earliest. It is suggested that apoptosis of mature leukocytes is a major cause of leukopenia development induced by chemotherapy. The simple technique of apoptosis-prone cell detection in whole blood may be effectively used in serial screening of hematological side-effects of chemotherapy.