Enhanced ex vivo apoptosis of peripheral granulocytes is a sufficient factor of neutropenia following myeloablative chemotherapy.
Fourteen patients with hemopoietic and solid malignancies underwent dose-intensive chemotherapy, followed by haemopoietic stem cell grafting. Granulocyte apoptosis was assessed as nuclear chromatin condensation, after ex vivo incubation of blood samples for 3 h, followed by Acridine Orange staining. Myeloablative therapy caused time-dependent increase in ex vivo granulocyte apoptosis, being maximal at D+7 to D+9, thus preceding the development of neutropenia (nadir values on D+13 to D+15). In vivo administration of G-CSF (Neupogen) resulted into short-term decrease in apoptotic granulocyte numbers. Hence, granulocyte apoptosis is an important factor of therapy-induced leukopenia and could be modified by the G-CSF treatment.
Chukhlovin
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A
Center of Haematology, St. Petersburg State Medical University, 6/8 L. Tolstoy St., St. Petersburg, Russia. bmt@spmu.rssi.ru
D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D001943:Breast Neoplasms / Q000628:therapy; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006098:Granulocytes / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000628:therapy; D006801:Humans; D007938:Leukemia / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D009503:Neutropenia / Q000139:chemically induced* / Q000188:drug therapy; D013997:Time Factors; D019172:Transplantation Conditioning
D019653:Myeloablative Agonists; D016179:Granulocyte Colony-Stimulating Factor