Biological and Clinical Correlates after Chemotherapy and Granulocyte Colony-Stimulating Factor Administration

Study Objective . To evaluate specific biological markers to improve understanding and use of granulocyte colony-stimulating factor (G-CSF) in patients receiving chemotherapy. Design . Prospective, randomized study. Setting . University-affiliated hospital and cancer center. Patients . Twenty-five patients randomized to begin G-CSF either 24 hours after chemotherapy (standard arm), or on the day the absolute neutrophil count (ANC) was below 1000/mm³ after chemotherapy (delayed arm). Interventions . To determine the effect of G-CSF on granulopoiesis, peripheral blood mononuclear cells were assayed by semisolid culture medium and flow cytometry for granulocyte progenitors and clonogenic CD34 antigen-positive cells. These biological markers were correlated with G-CSF administration schedules and the ANC. Measurements and Main Results . The effect of timing of G-CSF administration on rate of neutrophil recovery, duration of neutropenia, length of G-CSF therapy, delays of chemotherapy cycles, and neutropenic fever events was evaluated. Regardless of G-CSF schedule or chemotherapy regimen, the appearance of mobilized hematopoietic progenitors begins at the neutrophil nadir and parallels granulocyte recovery. Our data also demonstrate that proper timing of G-CSF administration produces similar rates of neutrophil recovery and comparable clinical outcomes. Conclusion . Based on the correlation between biological markers and ANC, we propose that the postchemotherapy ANC is a surrogate marker of renewed granulopoietic activity. The relevance of this finding in relationship to the clinical application of G-CSF remains to be further defined.