Background: Circulating hematopoietic peripheral blood progenitor cells (PBPCs) may contribute to the regeneration of nonhematopoietic organs. An increase in circulating PBPC numbers may enhance this process. Therefore, an exploratory trial of repeated PBPC mobilization in patients with chronic heart failure was conducted. The safety and cardiovascular efficacy data have been described elsewhere. In the hematopoietic system, the trial offered an opportunity to study several new aspects of granulocyte-colony-stimulating factor (G-CSF) action.
Study design and methods: Fourteen male patients with chronic heart failure were treated successively with G-CSF (four 10-day treatment periods interrupted by treatment-free intervals of equal length; daily dose adjustment to maintain a white blood cell [WBC] count of 45 x 10(9)-50 x 10(9)/L).
Results: G-CSF induced a rapid increase in cells of all WBC lineages with return to levels equal to (neutrophilic, eosinophilic, and basophilic granulocytes) or lower than those before treatment (monocytes, lymphocytes) during the treatment-free intervals. Red cell counts remained unchanged, but platelet counts decreased followed by rebound thrombocytosis. The extent of CD34+ cell mobilization was highly variable. For each patient, the changes induced were identical through all cycles, but the G-CSF dose required in the first cycle was significantly higher than in subsequent cycles. In the cohort of patients, an inverse correlation was observed between the WBC level reached and the dose of G-CSF administered.
Conclusions: Rapid alternation between PBPC mobilization and recovery periods is feasible, with identical alterations in all treatment cycles. G-CSF responsiveness varies among patients and is increased by pretreatment with G-CSF.