Plasma levels of granulocyte colony-stimulating factor in patients after allogeneic bone marrow transplantation for chronic myeloid leukemia correlate with engraftment of transplanted marrow

Abstract

Granulocyte colony-stimulating factor (G-CSF) is considered to play a pivotal role in hemopoietic regulation. Its pharmacological application is reported to shorten chemotherapy-induced neutropenia as well as time to engraftment in patients after bone marrow transplantation (BMT). In order possibly to establish further rationale for G-CSF treatment strategies in patients undergoing BMT, we evaluated G-CSF plasma levels of 89 patients after allogeneic BMT for chronic myeloid leukemia (CML). EDTA anti-coagulated plasma samples were collected starting on day -1 (before grafting) and thereafter twice weekly for four consecutive weeks. G-CSF levels were estimated by enzyme immunoassay. Patients with late (> 30 days) bone marrow engraftment had consistently higher G-CSF levels at day +1 (after grafting) compared to patients with early (< or = 30 days) engraftment, while all patients had low plasma levels on day -1/0. Mean G-CSF plasma levels and time to engraftment were correlated (r = 0.79). In univariate analyses, high G-CSF levels at days +1, +4, +7, +10 and several clinical variables (such as TBI, unrelated donor transplant, state of disease) were predictive of late engraftment. Further analysis by multivariate Cox regression resulted in the following predictive model: high G-CSF plasma levels at day +7 and +10 (after grafting), in combination with a blastic phase of the disease were highly predictive of late engraftment. The significantly higher G-CSF levels in patients with impaired engraftment may reflect early compensating mechanisms of the hemopoietic system, which should be investigated further.