BIOLOGICAL AND CLINICAL CORRELATES AFTER CHEMOTHERAPY AND GRANULOCYTE-COLONY-STIMULATING FACTOR ADMINISTRATION

Study Objective. To evaluate specific biological markers to improve un derstanding and use of granulocyte colony-stimulating factor (G-CSF) i n patients receiving chemotherapy. Design. Prospective, randomized stu dy. Setting. University-affiliated hospital and cancer center. Patient s. Twenty-five patients randomized to begin G-CSF either 24 hours afte r chemotherapy (standard arm), or on the day the absolute neutrophil c ount (ANC) was below 1000/mm(3) after chemotherapy (delayed arm). Inte rventions. To determine the effect of G-CSF on granulopoiesis, periphe ral blood mononuclear cells were assayed by semisolid culture medium a nd flow cytometry for granulocyte progenitors and clonogenic CD34 anti gen-positive cells. These biological markers were correlated with G-CS F administration schedules and the ANC. Measurements and Main Results. The effect of timing of G-CSF administration on rate of neutrophil re covery, duration of neutropenia, length of G-CSF therapy, delays of ch emotherapy cycles, and neutropenic fever events was evaluated. Regardl ess of G-CSF schedule or chemotherapy regimen, the appearance of mobil ized hematopoietic progenitors begins at the neutrophil nadir and para llels granulocyte recovery. Our data also demonstrate that proper timi ng of G-CSF administration produces similar rates of neutrophil recove ry and comparable clinical outcomes. Conclusion. Based on the correlat ion between biological markers and ANC, we propose that the postchemot herapy ANC is a surrogate marker of renewed granulopoietic activity. T he relevance of this finding in relationship to the clinical applicati on of G-CSF remains to be further defined.