Circulating granulocyte colony-stimulating factor (G-CSF) levels after allogeneic and autologous bone marrow transplantation: endogenous G-CSF production correlates with myeloid engraftment [see comments]

Abstract

Myeloid engraftment after bone marrow transplantation (BMT) is influenced by a number of variables, including cytoreductive chemoradiotherapy, genetic disparity, number of reinfused committed myeloid progenitor cells, healthy microenvironment, and the presence of hematopoietic growth factors. Granulocyte colony-stimulating factor (G- CSF) stimulates proliferation of myeloid progenitor cells and enhances myeloid engraftment after BMT. We investigated the temporal relationship between endogenous G-CSF production and myeloid engraftment in both children and adults after allogeneic (ALLO) and autologous (AUTO) BMT. Circulating endogenous G-CSF levels ranged between 0 and 2552 pg/mL. The correlation coefficient between circulating serum G-CSF levels and the peripheral absolute neutrophil count (ANC) was r = -.875 (P less than .001). The endogenous serum G- CSF level was highest during the first week after BMT, when the ANC was less than or equal to 200/microL (699 +/- 82.3 pg/mL) (P less than .001). Both children and adults demonstrated a similar inverse relationship between circulating G-CSF level and degree of neutropenia. One patient failed to engraft after AUTO BMT and also failed to generate any endogenous G-CSF production. Lastly, once the serum G-CSF level decreased to less than 200 pg/mL, a mean of 6.1 +/- 0.9 days elapsed before the ANC was greater than or equal to 500/microL for 2 consecutive days. This study demonstrates that endogenous G-CSF production is associated with myeloid engraftment in both children and adults after AUTO and ALLO BMT and that the rate of increase and decrease in endogenous G-CSF may be predictive of either failure to engraft or duration of neutropenia.

The endogenous granulocyte colony‐stimulating factor response following autologous peripheral blood stem cell transplantation is impaired in patients with myeloma

“…The significantly raised endogenous production of G‐CSF seen in our patients and noted by other authors in neutropenic situations (Cairo et al , 1992; Haas et al , 1994 ) did not reach the levels found in children (Saito et al , 1999 ) . Raised G‐CSF levels were inversely correlated with the number of days on which therapeutic G‐CSF, started on d 8, was required to reach a neutrophil count of 1·0 × 10 9 /l.…”

Concise Review: The Bone Marrow Niche as a Target of Graft Versus Host Disease

“…Drugs that have been approved for stimulating individual hematopoietic lineages except for B and T cells are commercially available and are routinely used beyond HSCT. Even in the context of allogeneic HSCT, the serum levels of erythropoietin (EPO), thrombopoietin (TPO), and granulocyte colony‐stimulating factor (G‐CSF) have been demonstrated to correlate inversely with the red blood cell, platelet, and neutrophil counts, respectively, thus reflecting normal physiological behavior . Only EPO levels have been described as inadequate for the anemia observed after MAC .…”

The Role of Cytokines and Adhesion Molecules for Mobilization of Peripheral Blood Stem Cells

“…In an intraindividual comparison, we observed a sevenfold greater yield of CD34 + cells per leukapheresis after G‐CSF‐supported chemotherapy compared with steady‐state administration of G‐CSF at a dose of 5 μg/kg/day [20]. This might be related to greater endogenous G‐CSF serum levels observed during chemotherapy‐induced neutropenia [21, 22]. It has been shown that myeloid precursor cells and mature neutrophils bind G‐CSF via high‐affinity receptors and therefore lead to a reduction of bioavailable G‐CSF [23].…”