Serum Granulocyte Colony-stimulating Factor Research Articles

Effect of continuous subcutaneous administration of a small dose of granulocyte colony stimulating factor (G-CSF) by the use of a portable infusion pump in patients with non-Hodgkin's lymphoma receiving chemotherapy.

The effects of continuous subcutaneous infusion (CSI) of human granulocyte-colony stimulating factor (G-CSF) on the absolute neutrophil count (ANC) and serum G-CSF level were examined in 11 patients with non-Hodgkin's lymphoma (NHL) during cytotoxic chemotherapy. Recombinant G-CSF (rG-CSF) was subcutaneously infused using a portable infusion pump at a constant flow rate of 1 microgram/20 microliters/h for 14 days starting 2 days after the end of the second course of chemotherapy. The ANC was lowered after the chemotherapy without rG-CSF infusion whereas the duration of neutropenia and the nadir level of the ANC after the chemotherapy were ameliorated by the combined administration of rG-CSF (mean +/- S.E., 0.6 +/- 0.5 days vs. 4.7 +/- 1.9 days, P < 0.05; 455 +/- 135/microliter vs. 1906 +/- 598/microliter, P < 0.05). Serum G-CSF levels increased after the start of rG-CSF infusion, reaching a mean peak value of 418.5 +/- 128.5 pg/ml at the 8th day, and then returned to the basal level (35.6 +/- 13.5 pg/ml) immediately after the end of continuous infusion of rG-CSF. Although a slight increase in serum G-CSF was obtained in the patients after the chemotherapy without rG-CSF administration, the mean serum level was much lower than that in the patients after the chemotherapy with rG-CSF administration (88.2 +/- 24.8 pg/ml vs. 199.6 +/- 20.6 pg/ml, P < 0.01). No notable side effects of the CSI of rG-CSF were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum levels of granulocyte-colony stimulating factor (G-CSF) in bacterial and viral infections, and in atypical pneumonia.

Serum granulocyte-colony stimulating factor (G-CSF) was measured with an ELISA method in patients with acute bacterial and viral infections, or with an atypical pneumonia. Before initiation of antibiotic treatment, G-CSF was found to be significantly increased (799 +/- 1501 ng/l) in sera from 34 patients with an acute bacterial infection compared with the 27 patients with a viral infection (58 +/- 34 ng/l; P < 0.001) and with the eight patients with an atypical pneumonia (60 +/- 33) ng/l; P < 0.001). No significant difference in G-CSF levels was seen between gram-positive and gram-negative bacterial infections. In septic shock, increased G-CSF levels were seen both in patients with leucocytosis and leucopenia. In uncomplicated bacterial infections, both G-CSF and IL-6 were increased on day 0, and decreased rapidly after initiation of antibacterial therapy and before the patients became afebrile. In bacterial infections on day 0, G-CSF levels correlated with mononuclear cells (rs = -0.62, P < 0.001), IL-6 (rs = 0.40, P < 0.05) and S-MPO (rs = -0.5, P < 0.01). In viral infections, G-CSF was correlated with mononuclear cells (rs = 0.41, P < 0.05), white blood cell counts (rs = 0.56, P < 0.01), neutrophils (rs = 0.41, P < 0.05) and CRP (rs = 0.47, P < 0.05). We conclude that G-CSF is rapidly raised in the blood in acute bacterial infections but not in acute viral infections or in infections with Mycoplasma pneumonia. Our results also support the theory that G-CSF is involved in the mechanisms of mobilization of neutrophils into the peripheral circulation.

Concentration of serum granulocyte colony-stimulating factor (SG-CSF) during chemotherapy-induced granulocytopenia in lung cancer patients assayed by chemiluminescence enzyme immunoassay (CLEIA) : S. Hashimoto, T. Takeuchi, A. Yoshii, Y. Fukuda, N. Ohsawa, First Department of Internal Medicine, Osaka Medical College, Osaka, Japan

Concentration of serum granulocyte colony-stimulating factor (SG-CSF) during chemotherapy-induced granulocytopenia in lung cancer patients assayed by chemiluminescence enzyme immunoassay (CLEIA) : S. Hashimoto, T. Takeuchi, A. Yoshii, Y. Fukuda, N. Ohsawa, First Department of Internal Medicine, Osaka Medical College, Osaka, Japan

Granulocyte and Granulocyte-Macrophage Colony-Stimulating Factors in Cord and Maternal Serum at Delivery

Impaired neutrophil responses contribute to the neonate's increased susceptibility to infection. Because granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) enhance granulocyte and macrophage number and function, their use in the management of neonatal sepsis may be beneficial. Little is known about the endogenous levels of G-CSF and GM-CSF. In adults, raised values for G-CSF, but not GM-CSF, have been demonstrated in patients with infection, and conflicting data has emerged regarding CSF levels in neonates. We have used an ELISA to measure maternal and cord serum G-CSF and GM-CSF at the time of delivery, with gestational age between 25 and 42 wk. In mothers, an inverse linear relationship between gestational age and GM-CSF levels (p = 0.049) was found, but no association with G-CSF levels was observed. In neonates, a quadratic association was found between GM-CSF levels and gestational age (p = 0.019), whereas G-CSF levels showed an inverse linear association (p = 0.015). In addition, an association was found between maternal and cord GM-CSF (p = 0.007) but not G-CSF levels in paired samples. The effect of gestational age on the cytokine levels could not be explained by the white cell count, the absolute neutrophil count, pregnancy-induced hypertension, or the presence of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Production of granulocyte colony-stimulating factor in vitro by monocytes from preterm and term neonates [see comments

We postulated that defective generation of granulocyte colony- stimulating factor (G-CSF) by cells of newborn infants might underlie their deficiencies in upregulating neutrophil production and function during bacterial infection. To test this, we isolated monocytes from the blood of preterm neonates, term neonates, and adults and, after stimulation with various concentrations of interleukin-1 alpha (IL-1 alpha) or lipopolysaccharide (LPS), quantified G-CSF concentrations in cell supernatants and G-CSF mRNA in cell lysates. When stimulated with plateau concentrations of IL-1 alpha for 24 hours, G-CSF concentrations were higher in supernatants of adult cells (8,699 +/- 5,529 pg/10(6) monocytes) than in those from term infants (2,557 +/- 442 pg, P &lt; .05) or from preterm infants (879 +/- 348 pg, P &lt; .05 v adults). When stimulated with plateau concentrations of LPS, supernatants of monocytes from preterm neonates had less G-CSF than did those from term neonates or adults. G-CSF mRNA content was low in cells from preterm infants, higher in those from term infants, and highest in those from adults. On the basis of the in vitro studies, we speculated that serum G-CSF concentrations might be less elevated in neutropenic neonates than in neutropenic adults. Indeed, serum concentrations were relatively low in all nonneutropenic subjects; 92 +/- 34 pg/mL (mean +/- SEM) in 10 preterm neonates, 114 +/- 21 pg/mL in 16 term neonates, and 45 +/- 13 pg/mL in 11 healthy adults. Serum concentrations were not elevated in 7 neutropenic neonates (39 +/- 17 pg/mL) but were in 8 neutropenic adults (2101 +/- 942 pg/mL, P &lt; .05 v healthy adults). Other studies suggested that the lower G-CSF production in neonates is not counterbalanced by a heightened sensitivity of G-CSF--responsive progenitors to G-CSF. Therefore, we speculate that newborn infants, particularly those delivered prematurely, generate comparatively low quantities of G-CSF after inflammatory stimulation, and that this might constitute part of the explanation for their defective upregulation of neutrophil production and function during infection.

Production of Granulocyte Colony-Stimulating Factor In Vitro by Monocytes From Preterm and Term Neonates

We postulated that defective generation of granulocyte colony-stimulating factor (G-CSF) by cells of newborn infants might underlie their deficiencies in upregulating neutrophil production and function during bacterial infection. To test this, we isolated monocytes from the blood of preterm neonates, term neonates, and adults and, after stimulation with various concentrations of interleukin-1 alpha (IL-1 alpha) or lipopolysaccharide (LPS), quantified G-CSF concentrations in cell supernatants and G-CSF mRNA in cell lysates. When stimulated with plateau concentrations of IL-1 alpha for 24 hours, G-CSF concentrations were higher in supernatants of adult cells (8,699 +/- 5,529 pg/10(6) monocytes) than in those from term infants (2,557 +/- 442 pg, P < .05) or from preterm infants (879 +/- 348 pg, P < .05 v adults). When stimulated with plateau concentrations of LPS, supernatants of monocytes from preterm neonates had less G-CSF than did those from term neonates or adults. G-CSF mRNA content was low in cells from preterm infants, higher in those from term infants, and highest in those from adults. On the basis of the in vitro studies, we speculated that serum G-CSF concentrations might be less elevated in neutropenic neonates than in neutropenic adults. Indeed, serum concentrations were relatively low in all nonneutropenic subjects; 92 +/- 34 pg/mL (mean +/- SEM) in 10 preterm neonates, 114 +/- 21 pg/mL in 16 term neonates, and 45 +/- 13 pg/mL in 11 healthy adults. Serum concentrations were not elevated in 7 neutropenic neonates (39 +/- 17 pg/mL) but were in 8 neutropenic adults (2101 +/- 942 pg/mL, P < .05 v healthy adults). Other studies suggested that the lower G-CSF production in neonates is not counterbalanced by a heightened sensitivity of G-CSF--responsive progenitors to G-CSF. Therefore, we speculate that newborn infants, particularly those delivered prematurely, generate comparatively low quantities of G-CSF after inflammatory stimulation, and that this might constitute part of the explanation for their defective upregulation of neutrophil production and function during infection.

Autonomous production of granulocyte-colony stimulating factor in tumour xenografts associated with leukocytosis.

Leukocytosis sometimes accompanies malignant neoplasms in the absence of infection. It is thought that the production of colony-stimulating factor by neoplasms is the most potent cause of tumour-induced leukocytosis; several mechanisms have been suggested to explain this. We examined 155 human tumour xenografts established in nude mice, and found that 17 of the xenografts induced remarkable leukocytosis (> 15,000 microliters-1) in nude rats. We examined granulocyte colony-stimulating factor (G-CSF) production by the xenografts to study the mechanisms underlying this tumour-induced leukocytosis. Ten of the 17 xenografted human tumours appeared to express the G-CSF gene. Serum G-CSF increased, to concentrations of 179-37,218 pg ml-1, in host animals transplanted with the ten xenografts expressing the G-CSF gene transcripts. The biological activity of serum G-CSF also increased, to concentrations of 206-9,074 pg ml-1, in the host animals transplanted with the ten xenografts. Immunohistochemical analysis demonstrated G-CSF production at the cellular level in three of the ten xenografts. These results suggested that the production of G-CSF is a common event in human tumour xenografts associated with leukocytosis, but that factors other than G-CSF are also likely to be involved. Leukocytosis induced by neoplasms seems to be a heterogeneous and complex disorder.

Disposition of recombinant human granulocyte colony-stimulating factor in children with severe chronic neutropenia

The disposition of recombinant human granulocyte colony-stimulating factor (G-CSF) was studied in 11 children with severe chronic neutropenia given 6 to 48 micrograms G-CSF per kilogram subcutaneously. Serum concentrations of G-CSF were measured by bioassay. Peak serum G-CSF concentrations were proportional to dosage and occurred 2 to 8 hours after subcutaneous administration. Nine of the eleven children had a significant increase in absolute neutrophil count (ANC). The median ANC in responding patients was 6.7 x 10(9)/L on day 14 versus 0.17 x 10(9)/L on day 1 of therapy (p < 0.01). The G-CSF clearance increased as ANC increased, and the relationship was well described by a sigmoid model. Maximal clearance approached 2 ml/min per kilogram at ANCs > 17.0 x 10(9)/L; minimal clearance was 0.29 ml/min per kilogram at ANCs of 0. The half-life of G-CSF was inversely related to ANC; mean half-life was 4.7 hours at ANCs of 0 but < 2 hours at ANCs greater than 17.0 x 10(9)/L. The two patients who failed to achieve a clinical response had no change in G-CSF clearance or half-life, nor did they have an increase in ANC when G-CSF dosages were escalated to 18 or 48 micrograms/kg twice a day. These results indicate that G-CSF pharmacokinetics are directly influenced by ANC; higher serum concentrations, slower clearances, and longer half-lives are associated with low ANCs.

Granulocyte Colony-Stimulating Factor Treatment of Antithyroid Drug-Induced Granulocytopenia

The primary objective of this study was to ascertain the effectiveness of granulocyte colony-stimulating factor in the treatment of antithyroid drug-induced granulocytopenia of varying degree. Sixteen patients with Graves' disease with antithyroid drug-induced granulocytopenia (granulocyte counts < 1.0 x 10(9)/L) each received a daily dose of 75 micrograms of granulocyte colony-stimulating factor administered subcutaneously. Within 24 hours of the first injection, the granulocyte count increased (0.6 to 12.3 x 10(9)/L) in all 10 patients with mild granulocytopenia (granulocyte counts between 0.5 and 1.0 x 10(9)/L) and all three with moderate granulocytopenia (granulocyte counts < 0.5 x 10(9)/L). The three remaining patients with severe granulocytopenia (agranulocytic), whose granulocyte counts were zero, did not recover from granulocytopenia until the 6th, 7th, and 14th days of treatment with granulocyte colony-stimulating factor. Examination of bone marrow taken at the onset of the disease in all three agranulocytic patients showed a prominent decrease in granulocytic series, while identical examination in six of eight patients with mild to moderate granulocytopenia showed close to normal granulocytic series. There was no elevation of serum granulocyte colony-stimulating factor concentration in four patients with mild granulocytopenia and one with moderate granulocytopenia at the onset of their disease, whereas those of the remaining three patients with severe granulocytopenia (agranulocytic) increased at onset of agranulocytosis. This information led us to conclude that: (1) granulocyte colony-stimulating factor is effective in the treatment of antithyroid drug-induced mild to moderate granulocytopenia and (2) in severe agranulocytic cases, granulocyte colony-stimulating factor is not effective. Accordingly, we were again reminded of the importance of early diagnosis and treatment of antithyroid drug-induced agranulocytosis.

Granulocyte colony-stimulating factor (CSF), macrophage-CSF, granulocyte-macrophage CSF, interleukin-3, and interleukin-6 levels in sera from children undergoing blood stem cell autografts

Endogenous production of granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin-3 (IL-3), and interleukin-6 (IL-6) was investigated in 10 children who underwent a total of 12 courses of autologous peripheral blood stem cell transplant (PBSCT) by measuring their serum levels using immunoassay kits. The serum G-CSF level increased immediately following infusion of PBSC graft, peaked between days 3 and 7 posttransplant and then declined by the time the granulocyte count rose. No definitive association was found between the continuous high levels of G-CSF and infective episodes, the number of infused nucleated cells, monocytes, CFU-GM, or the number of days required to achieve greater than 0.5 x 10(9)/L granulocyte, greater than 1.0 x 10(9)/L leukocyte, or greater than 50 x 10(9)/L platelet counts. After PBSCT, IL-6 levels tended to be elevated. No detectable serum level of GM-CSF or IL-3 (&lt; 50 pg/mL) was observed before PBSCT and 4 patients showed a transient increase in the GM-CSF level after PBSCT. No significant change was observed in the post-transplant serum levels of IL-3 or M- CSF. The role of endogenously secreted cytokines in early hematopoietic recovery after PBSCT needs further clarification, but, at present, routine use of exogenous G-CSF therapy is not recommended.

Granulocyte Colony-Stimulating Factor (CSF), Macrophage-CSF, Granulocyte-Macrophage CSF, Interleukin-3, and Interleukin-6 Levels in Sera From Children Undergoing Blood Stem Cell Autografts

Endogenous production of granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin-3 (IL-3), and interleukin-6 (IL-6) was investigated in 10 children who underwent a total of 12 courses of autologous peripheral blood stem cell transplant (PBSCT) by measuring their serum levels using immunoassay kits. The serum G-CSF level increased immediately following infusion of PBSC graft, peaked between days 3 and 7 posttransplant and then declined by the time the granulocyte count rose. No definitive association was found between the continuous high levels of G-CSF and infective episodes, the number of infused nucleated cells, monocytes, CFU-GM, or the number of days required to achieve greater than 0.5 x 10(9)/L granulocyte, greater than 1.0 x 10(9)/L leukocyte, or greater than 50 x 10(9)/L platelet counts. After PBSCT, IL-6 levels tended to be elevated. No detectable serum level of GM-CSF or IL-3 (< 50 pg/mL) was observed before PBSCT and 4 patients showed a transient increase in the GM-CSF level after PBSCT. No significant change was observed in the post-transplant serum levels of IL-3 or M-CSF. The role of endogenously secreted cytokines in early hematopoietic recovery after PBSCT needs further clarification, but, at present, routine use of exogenous G-CSF therapy is not recommended.

Levels of serum granulocyte colony-stimulating factor in patients with chronic myeloid leukemia.

To clarify the patho-physiologic role of granulocyte colony-stimulating factor (G-CSF) in chronic myeloid leukemia (CML), we determined the serum levels of G-CSF in various stages of CML using a very sensitive method: chemiluminescence enzyme immunoassay (CLEIA). This method makes it possible to estimate very low levels of serum G-CSF. In the present study, serum samples from 25 patients in chronic phase and 16 in blastic crisis, as well as samples from 33 healthy volunteers were investigated. The serum G-CSF levels in chronic phase of CML (2.95 +/- 3.91 pg/ml) were significantly lower than those in normal controls (15.92 +/- 6.53 pg/ml) and in blastic crisis of CML (15.52 +/- 17.65 pg/ml) within a range of very low levels (p < 0.001, p < 0.02). Moreover, a reverse correlation between blood neutrophil counts and serum G-CSF levels were clearly demonstrated for CML including blastic crisis (r = 0.405, p < 0.02). Interestingly, a sequential parallel relation was observed between serum G-CSF levels and neutrophil alkaline phosphatase (NAP) scores for a patient with CML in chronic phase. Our observations indicate that a negative feedback mechanism exists between peripheral neutrophils and serum G-CSF levels in the chronic phase of CML, and that very low levels of G-CSF in chronic phase of CML might be an important cause for the low NAP scores.

Levels of serum granulocyte colony-stimulating factor in patients with cerebrovascular diseases

The role of leukocytes in the pathogenesis of cerebrovascular disease, in particular, cerebral ischemic disease has recently become a focus of research, Several studies have reported that a positive correlation between increased functional activities of neutrophils and the risk of cerebral ischemic disease. Granulocyte colony-stimulating factor (G-CSF) is known to be not only a granulocyte proliferating but also a potent activator of mature neutrophils. In this study, we measured the serum G-CSF levels in 143 patients with cerebrovascular diseases and in 100 patients with other diseases, using our established enzyme-linked immunosorbent assay (ELISA) for G-CSF The minimal detection level was 20 pg/ml G-CSF. In patients with cerebral infarction, G-CSF could be detected in 18.3% and in patients with cerebral hemorrhage, it could be detected in 9.8% of analyzed samples. On the other hand, 6% of the patients with other diseases had measurable levels of G-CSF. The differences among these three groups were statistically significant according to the χ2 test (p <0.01). Our findings that there was a significantly high frequency of elevated levels of G-CSF among patients with cerebrovascular diseases, may indicate that the action of G-CSF as a potent activator of neutrophils plays some role in the occurrence of cerebrovascular disease, in particular, cerebral infarction.

食道癌術後のか粒球機能の変動と血中ｇｒａｎｕｌｏ ｃｙｔｅｃｏｌｏｎｙ‐ｓｔｉｍｕｌａｔｉｎｇ ｆａｃｔｏｒ値の意義

開胸, 開腹を伴う食道癌術後の末梢血顆粒球機能と, 顆粒球の主たる増殖刺激因子であるgranulocyte colony-stimulating factor (G-CSF) の血中濃度の関連を究明するために, 食道癌症例 (E群, n=12) と胃亜全摘術を施行した胃癌症例 (G群, n=12, 対照) に対して, 術前および術後, 経時的に末梢血の自血球数 (WBC), 類粒球数 (GC), 顆粒球化学発光量 (CL), G-CSF値 (G-CSF) を測定した. E群のWBC, GCはG群に比べ, 術後4, 8時間において有意の低値を示し (p<0.01), CLは術後4, 8, 24時間後に有意の低値を呈した (p<0.05). しかし, E群のG-CSFはG群に比べ, 4, 8時間後に有意の高値を呈し (p<0, 01), 術後4, 8時間におけるPMNとG-CSFの間には有意な負の相関が認められた (p<0.01), 以上より食道痛術後早期にはG-CSFをはじめとするサイトカインの過乗Jな刺激により, 頼粒球の組織への接着, 遊出の増加をきたし, 末梢血類粒球の数, CL値の低下状態が生じていることが類推された.

Serum granulocyte colony-stimulating factor in patients with repeated infections.

We have already reported significant elevation of serum granulocyte colony-stimulating factor (G-CSF) in the acute phase of infection. In this study, we compared the responses to infection between patients with frequently repeated infection (repeaters) and others (non-repeaters). We examined the clinical data and serum G-CSF levels in 48 patients with acute infections. Serum G-CSF levels were significantly lower in repeaters than in non-repeaters (197.7 +/- 370.0 vs. 1014.1 +/- 924.4 pg/ml. P less than 0.001). There were no significant differences in age, serum total protein, or cholinesterase between the groups, but serum albumin was significantly lower in repeaters than in non-repeaters (2.87 +/- 0.5 vs. 3.31 +/- 0.4 g/dl. P less than 0.005). It is suggested that administration of recombinant G-CSF may be useful for patients with repeated infections.

Levels of human serum granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor under pathological conditions

Levels of serum granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with various leukocyte disorders were estimated by enzyme-linked immunosorbent assay (ELISA). Some cases of acute myelogenous leukemia and aplastic anemia showed elevated serum levels of G-CSF and/or GM-CSF, whereas almost all of 23 healthy controls showed G-CSF and GM-CSF levels lower than 100 pg/ml. High levels of both types of CSF were noted in patients with granulocytosis due to infection. These levels became lower after resolution of the infection. Daily changes in serum CSF levels were also examined in a patient with autoimmune neutropenia, and it was found that the peripheral neutrophilic granulocyte count changed almost in parallel with the serum G-CSF level but not with GM-CSF, following the pattern with a delay of about 4-5 h, suggesting the possibility that G-CSF mainly regulates peripheral neutrophil circulation.

Effect of endotoxin on serum granulocyte and granulocyte-macrophage colony-stimulating factor levels in dogs.

The biologic effects of endotoxin are attributed to the release of several cytokines, including interleukin-1, interleukin-6, tumor necrosis factor, and the colony-stimulating factors. To investigate the mechanism of endotoxin-induced neutrophilia in dogs, several cell lines known to proliferate selectively in response to recombinant human colony-stimulating factors were examined to determine their responses to recombinant canine granulocyte colony-stimulating factor (rcG-CSF) or recombinant canine granulocyte-macrophage colony-stimulating factor (rcGM-CSF). The murine cell line NFS-60 was found to respond well to rcG-CSF and the human cell line TALL-101 to rcGM-CSF, and these responses were neutralized by antibodies to these recombinant proteins. These bioassays were then used to determine G-CSF and GM-CSF levels in dogs after intravenous endotoxin administration. G-CSF levels increased by 2 h, peaked at 4 h, and had not returned to normal by 24 h after endotoxin. In contrast, GM-CSF was not detectible before or after endotoxin administration.

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

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.

Circulating Granulocyte Colony-Stimulating Factor (G-CSF) Levels After Allogeneic and Autologous Bone Marrow Transplantation: Endogenous G-CSF Production Correlates With Myeloid Engraftment

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 level of serum granulocyte colony-stimulating factor in cancer patients with leukocytosis.

The level of serum granulocyte colony-stimulating factor (G-CSF) obtained from patients with leukocytosis (greater than 10,000/microliters) between May 1989 and April 1991 was measured by enzyme immunoassay. Studied were 18 patients with malignant neoplasms (median age, 64 years) and 14 patients with hematologic disease (median age, 59 years). Increased serum G-CSF values ranging from 70 to 374 pg/ml were noted in 7 of 15 lung cancer cases, a case of malignant thymoma and a blastic crisis of chronic myelogenous leukemia. The rest of the cases showed a normal value (less than 60 pg/ml). There was no correlation between the neutrophil count and G-CSF level. In lung cancer cases with high G-CSF values, neither a characteristic histologic type nor common elevation of tumor markers could be seen. The neutrophil alkaline phosphatase score was significantly increased and hypercalcemia was presented in high G-CSF cases. G-CSF may contribute at least in part to unknown leukocytosis observed in malignant neoplasms, especially in lung cancer.