Haemopoietic cell kinetics in humans treated with rGM‐CSF

We have investigated the kinetics of myeloid cell proliferation in the marrow of patients with small‐cell lung cancer and treated with 10 daily subcutaneous injections of granulocyte/macrophage colony‐stimulating factor (GM‐CSF). Bone marrow, obtained before and during treatment with the growth factor, was labelled in vitro with tritiated thymidine (³H‐TdR). A 3rd bone‐marrow sample was obtained I hr following an intravenous injection of ³H‐TdR. Subsequent daily blood samples were also collected, and ³H‐TdR labelling was assessed on these and the marrow preparations by autoradiography. GMCSF treatment increased the peripheral granulocytic cells nearly 5‐fold, but this included significant eosinophilia, so that the neutrophilic granulocytes increased only 3.3‐fold. These cells were released from the marrow over a normal time scale, but their peripheral half‐life was about 6 times longer than normal and they were probably functionally defective. Furthermore, significant numbers of immature cells were released from the marrow. Neutrophil production stimulated by GM‐CSF was thus overestimated by measurement of the apparent peripheral granulocytosis. Increased labelling indices and grain counts in the proliferating granulocytic cells of the marrow indicate shortened cell‐cycle times, and the excess granulocyte production appears to be the result of extra amplification divisions in the proliferative compartments.