BACKGROUND: Peripheral blood progenitor cells collected from normal donors after granulocyte- colony stimulating factor (G-CSF) treatment are increasingly used for allogeneic transplantation. Previously, we investigated the mobilization kinetics of CD34+/Thy-1dim progenitor cells during subcutaneous administration of G-CSF in normal donors (Transfusion 1997;37:406-10). Although it is considered to be a relatively safe procedure, there are still uncertainties about the most efficient method of progenitor cell mobilization. Due to the short elimination half-life of G-CSF of about 3-4 hours we considered the subcutaneous administration of G-CSF once or twice daily might be suboptimal. The aim of the present study is to evaluate the mobilization kinetics of CD34+ cells during continuous intravenous (IV) administration of G-CSF in normal donors. METHODS: Fifteen healthy donors were enrolled in this study. The median age was 38 years (range, 20-56). G-CSF (Filgrastim, 10 microgram/kg/day) was administered for 4 consecutive days through continuous IV infusion. Then, we collected PBPC on the day following the 4th dose of G-CSF using a blood cell separator. For measurement of complete blood counts and CD34+ cell levels, peripheral blood sampling was performed immediately before the administration of G-CSF (steady-state) and after 4, 8, 24, 48, 72, 96, 120 hours of continuous IV administration of G-CSF. RESLUTS: After continuous IV administration of G-CSF, the WBC counts increased up to day 5 and reached approximately 8.4-fold above the steady-state level. Changes in the granulocyte count were similar to those in WBC counts. The number of lymphocytes increased up to day 4 (2.7-fold above the steady-state level), but no further increase occurred on day 5. Although there were considerable variations among the healthy donors, the statistical peaks of CD34+ cell levels were consistently observed on day 3 or day 4. Up to the fourth day of G-CSF treatment, the circulating CD34+ cells expanded by 25-fold. The percentage and absolute number of CD34+ cells significantly increased on day 3 (0.55 +/- 0.09%, 51.12 +/- 24.83x103/mL) and day 4 (0.47 +/- 0.09%, 46.66 +/- 24.93x103/mL), compared with steady-state values (0.06 +/- 0.09%, 2.03 +/- 5.69x103/mL). CONCLUSION: Our results showed that continuous IV administration of G-CSF apparently results in more rapid mobilization of CD34+ cells at least 24-48 hours compared with daily subcutaneous administration of G-CSF in normal donors.
Administration, Intravenous* ; Blood Cell Count ; Blood Cells ; Colony-Stimulating Factors ; Granulocyte Colony-Stimulating Factor* ; Granulocytes ; Half-Life ; Humans ; Kinetics* ; Lymphocytes ; Stem Cells ; Tissue Donors* ; Transplantation, Homologous

BACKGROUND: Transplantation of allogeneic peripheral blood stem cells (PBSCs) may have advantage over bone marrow transplantation with regards to the speed of hematopoietic and immunologic recovery. Recently to overcome the need for multiple leukaphereses to collect enough PBSCs for autologous transplantation, large volume leukaphereses (LVL) are used to process multiple blood volumes per session. Experience with this technique in healthy individuals after mobilization with colony stimulating factor (CSF) is limited. We have investigated the efficacy and safety of LVL for the collection of G-CSF and GM-CSF mobilized PBSCs from healthy donors. METHODS: This study was done on 40 healthy donors who were mobilized with G-CSF and GM-CSF for allogeneic peripheral blood stem cells transplantation (allo-PBSCT). After 5 days of mobilization treatment, PBSCs were collected by LVL with Fenwal CS-3000 Plus (Baxter Co, USA). In LVL, heparin was administered in addition to ACD-A. Patients underwent of LVL procedures daily to obtain a target cell dose of >or= 4x10(8)/kg MNCs and >or= 6x10(6)/kg CD34+ cells. RESULTS: 66 LVL procedures were done on 40 donors. Of these donors, 31 (77.5%) reached the collection target with one leukapheresis. The product per LVL contained a mean 5.79+/-2.47 10(8)MNCs/kg and 11.6+/-10.62x10(6) CD34+ cells/kg respectively. Mean percentages of MNC were 79.88+/-22.15% and collection efficiencies of MNCs were inversely related to the starting MNC count (r=-0.536, P<0.001). After LVL, although none of the donors exhibited bleeding complications, platelets decreased from 187.4+/-52.68x10(3)/microL to 74.88+/-13.7x10(3)/microL and activated partial thromboplastin time (APTT) prolonged from 29.13+/-3.77 seconds to 67.51+/-54.26 seconds. CONCLUSION: We conclude that LVL after mobilization treatment with G-CSF and GM-CSF in normal healthy donors was tolerable and efficient methods for PBSCs collection, but long-term risk of adverse effects in normal donors needs to be carefully addressed by individual institutions as well as national and international registries.
Autografts ; Blood Volume ; Bone Marrow Transplantation ; Colony-Stimulating Factors ; Granulocyte Colony-Stimulating Factor ; Granulocyte-Macrophage Colony-Stimulating Factor ; Hemorrhage ; Heparin ; Humans ; Leukapheresis* ; Partial Thromboplastin Time ; Registries ; Stem Cells* ; Tissue Donors ; Transplantation, Autologous

BACKGROUND: The use of colony stimulating factor (CSF) has increased to mobilize hematopoietic progenitor cells for allo-PBSCT. The most effective mobilization regimen has not yet defined. The authors analyzed the results of the mobilized PBSC collection through large volume leukapheresis from 38 normal healthy donors using three different regimens, namely, a single regimen with GM-CSF (Leucogen ), a concurrent use of GM-CSF and G-CSF (Leucostim ), and a sequential regimen with GM-CSF followed by G-CSF. METHODS: This study was done on 38 healthy donors from Sep. 1998 to Jan. 2001. One donor was mobilized with G-CSF alone, 9 with GM-CSF alone, 20 with concurrent regimen and 8 with sequential regimen. After 5 days of mobilization treatment, PBSCs were collected by large volume leukapheresis through femoral vein catheter. We compared the results of each collected progenitor cells and observed the side effects. RESULTS: The average WBC count before apheresis was 22.6+-11.0x103/uL and circulating CD34+cell percent was 1.31+-2.24%. Total 66 times with an average of 1.46+-0.61 of largevolume leukapheresis were performed for the 37 donors. The mean collected MNC count was 4.61+-2.77x108/kg, CD3+cell count was 2.95+-1.82x108/kg and CD34+cell count was 9.76+-12.42x106/kg. A significant side effect observed after large volume leukapheresis was thrombocytopenia showing decrease from 199.1+-52.2 to 80.7+-25.2x103/uL without any bleeding tendency. The mean collected MNC counts provoed to be significantly higher in combination groups with GM-and G-CSF than GM-CSF alone (P<0.05). The CD34+cell counts showed to be statistically higher in a sequential group compared to the concurrent and single regimen groups (P<0.05). CONCLUSION: A mobilization protocol with combination regimens of GM-CSF and G-CSF seemed to be superior to a single regimen with GM-CSF. Large volume leukapheresis through femoral vein catheter after mobilization with combination regimens of GM-and G-CSF in normal healthy donors was safe and proved to be an excellent. method to harvest stem cells.
Blood Component Removal ; Catheters ; Colony-Stimulating Factors ; Femoral Vein ; Granulocyte Colony-Stimulating Factor* ; Granulocyte-Macrophage Colony-Stimulating Factor* ; Hematopoietic Stem Cells ; Hemorrhage ; Humans ; Leukapheresis* ; Stem Cells* ; Thrombocytopenia ; Tissue Donors*

Administration of G-CSF may not always respond in rise of neutrophil counts in different patient population. In order to understand a possible inter-relationship between the G-CSF and GM-CSF induced leukocyte responses and expression levels of receptors for G-CSF (G-CSFr) and GM-CSF (GM-CSFr), the levels of each receptor and CSF were measured in patients with basophilia (8), eosinophilia (14) and bacterial infection showing neutrophilia (12) in comparison with normal healthy adults (12) and children (14). G-CSFr was expressed in neutrophils in the largest amount followed by monocytes, but GM-CSFr was expressed more in monocytes than neutrophils. Lymphocytes and basophils did not express G-CSFr or GM-CSFr. The amount of GM-CSFr in neutrophils was present less in patients with infection than normal control (P = 0.031). The neutrophils expressed more G-CSFr than GM-CSFr. The quantity of G-CSFr in eosinophil showed marked interval change, higher in acute stage. The plasma concentrations of G-CSF in patients with infection were much higher than normal adults or children (117.95 +/- 181.16 pg/ml, P < 0.05). Binding assay with excess amount of CSFs could discriminate the patient who did not show any response to G-CSF or GM-CSF administration. After incubation with excess CSFs, more receptors were blocked in children than in adults (G-CSF P = 0.024, GM-CSF P = 0.006). These results indicate that the amount of CSFr in leukocyte varies in different types of leukocyte, and changes according to the patients' condition even in the same type of leukocyte, and the CSFrs of children bind to CSFs more than those of adults.
Adult ; *Bacterial Infections ; Basophils/chemistry ; Breast Neoplasms ; Child ; Colony-Stimulating Factors/*blood ; Eosinophilia ; Human ; Leukemia, Myeloid, Chronic ; *Leukocyte Disorders ; Monocytes/chemistry ; *Neoplasms ; Neutrophils/chemistry ; Receptors, Colony-Stimulating Factor/*analysis ; Receptors, Granulocyte Colony-Stimulating Factor/analysis ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/analysis

PURPOSE: Current intensive anticancer therapy may cause myelosuppression with an increased risk of severe infections. As a result, the administration of chemotherapy in cancer patients might be delayed often. Hemopoietic growth factors, which are responsible for the differentiation and functional regulation of granulocytes and monocytes, have been cloned and are available as rhG-CSF and rhGM-CSF. The aim of this study was to compare the efficacy and side effects of rhG-CSF and rhGM-CSF in children with cancer who received chemotherapy. METHODS: The study included 55 children ranging in age from 2 to 18 years who received chemotherapy for cancer and had absolute neutrophil count (ANC) under 500/muL. The growth-factors were administered subcutaneously starting in doses of 5~10 mug/ kg/day. The ANC was determined by complete blood counts starting on the first day of administration and every other day thereafter until the ANC rose above 1,000/muL. RESULTS: There was no significant difference in the mean days for increase of the mean ANC value >500/muL (5.0+/-2.9 vs 5.7+/-4.2 days) and >1,000/muL (5.9+/-3.2 vs 6.4+/-4.8 days) after rhG-CSF and rhGM-CSF respectively. Side effects of rhG-CSF and rhGM-CSF were fever, myalgia, bone pain, elevation of ALT and rGT and abdominal pain in order and there was no difference between two growth factors. Also the numbers of transfusion of packed RBCs (0.7+/-0.8 vs 0.7+/-0.8) and platelets (0.8+/-1.0 vs 0.6+/-0.9) were not different after the two growth factors. CONCLUSION: It seems to be that rhG-CSF and rhGM-CSF are comparable in clinical effects and side effects when used for granulocytopenia in children with cancer.
Abdominal Pain ; Agranulocytosis ; Blood Cell Count ; Child* ; Clone Cells ; Colony-Stimulating Factors* ; Drug Therapy ; Fever ; Granulocyte-Macrophage Colony-Stimulating Factor* ; Granulocytes* ; Humans* ; Intercellular Signaling Peptides and Proteins ; Monocytes ; Myalgia ; Neutropenia ; Neutrophils

BACKGROUND: Granulocyte colony stimulating factor (G-CSF) is known as a cytokine central to the hematopoiesis of blood cells and to modulate their cellular functions. Besides granulocytes and their precursors, monocytes/macrophages and endothelial cells are direct target cells of G-CSF action. G-CSF influences immune cells in an anti-inflammatory way. METHODS: To evaluate whether G-CSF has a potential for preventing or ameliorating diseases characterized by mucosal inflammation, we used a mouse model with trinitrobenzene sulfonic acid (TNBS)-induced inflammatory colitis. To the mice model G-CSF was administrated daily by intraperitoneal injection. Macroscopic evaluation and immunohistochemical analysis of colonic tissues were performed. RESULTS: Recombinant human G-CSF significantly inhibited LPS-induced TNF-alpha mRNA expression in THP-1 cells. As for in vivo relevance, G-CSF dramatically reduced the weight loss of mice, colonic damage, and mucosal ulceration that characterize TNBS colitis. Moreover, G-CSF suppressed the expression of tumor necrosis factor-alpha, interleukin-1beta, and intercellular adhesion molecule-1 in TNBS colitis. CONCLUSION: Current results demonstrate that G-CSF may be an effective agent for the treatment of diseases characterized by mucosal inflammation.
Animals ; Blood Cells ; Colitis* ; Colon ; Colony-Stimulating Factors* ; Endothelial Cells ; Granulocyte Colony-Stimulating Factor ; Granulocytes* ; Hematopoiesis ; Humans ; Inflammation ; Inflammatory Bowel Diseases ; Injections, Intraperitoneal ; Intercellular Adhesion Molecule-1 ; Interleukin-1beta ; Mice* ; RNA, Messenger ; Tumor Necrosis Factor-alpha ; Ulcer ; Weight Loss

In our study, a two-phase culture system was developed to acquire large amount of CD41+ and polyploidy cells. Human mobilized peripheral blood CD34+ (PB CD34+) cells were first cultured in expansion medium (Cocktail or CC100 medium) for 3,4,5 or 6 days, and then cultured in megakaryocytic differentiation medium containing TPO and SCF for additional 7, 8 or 9 days. Cell expansion, morphology, CD41+ cell percentage and DNA content were investigated to evaluate the protocol. The result showed that more CD41+ and polyploidy cells could be obtained following the two-phase culture with Cocktail medium than with CC100. Moreover, with 3 days expansion in Cocktail medium plus 7 days in differentiation medium, the initial CD 34+ cells obtained 16-fold expansion of CD41+ cells and 3-fold expansion of polyploidy cells, such obtained level being significantly higher than that of culturing cells with only one step in TPO or TPO+SCF. We conclude that with the two-phase culture system, PB CD34+ cells can expand and differentiate to more CD41+ and polyploidy cells than those cultured only in accordance to the one-stage culture protocol, so a new and highly efficient megakaryocyte differentiation model for megakaryocyte and platelet related researches is provided already.
Antigens, CD34 ; blood ; Blood Cells ; cytology ; Cell Culture Techniques ; methods ; Cell Differentiation ; physiology ; Colony-Stimulating Factors ; physiology ; Hematopoietic Stem Cell Mobilization ; methods ; Humans ; Megakaryocytes ; cytology ; Stem Cells ; cytology

Colchicine poisoning is rare but can cause potentially life-threatening toxic complications such as hypovolemic shock, cardiovascular collapse and multiple organ failure. In this case report, we describe a case of a 20-year-old female who presented to the emergency department after suicidal ingestion of a toxic dose of colchicine. She developed thrombocytopenia, neutropenia and acute respiratory distress syndrome that required blood transfusion and administration of granulocyte colony stimulating factor for the prevention of infectious complications. With regard to the clinical manifestations of colchicine toxicity, we discussed suggested mechanisms.
Blood Transfusion ; Colchicine* ; Colony-Stimulating Factors* ; Eating ; Emergency Service, Hospital ; Female ; Granulocytes* ; Humans ; Multiple Organ Failure ; Neutropenia ; Poisoning* ; Respiratory Distress Syndrome, Adult ; Shock ; Thrombocytopenia ; Young Adult

Colchicine poisoning is rare but can cause potentially life-threatening toxic complications such as hypovolemic shock, cardiovascular collapse and multiple organ failure. In this case report, we describe a case of a 20-year-old female who presented to the emergency department after suicidal ingestion of a toxic dose of colchicine. She developed thrombocytopenia, neutropenia and acute respiratory distress syndrome that required blood transfusion and administration of granulocyte colony stimulating factor for the prevention of infectious complications. With regard to the clinical manifestations of colchicine toxicity, we discussed suggested mechanisms.
Blood Transfusion ; Colchicine ; Colony-Stimulating Factors ; Eating ; Emergency Service, Hospital ; Female ; Granulocytes ; Humans ; Multiple Organ Failure ; Neutropenia ; Poisoning ; Respiratory Distress Syndrome, Adult ; Shock ; Thrombocytopenia ; Young Adult

BACKGROUND: Major burn injury induces an inflammatory response that is accompanied by the release of various cytokines. We investigated the gradual changes in the levels of pro-inflammatory and anti-inflammatory cytokines following burn injury and determined the relationship between these levels and burn size in adult Korean patients with burn injury. METHODS: Blood samples from 9 healthy controls and 60 Korean burn patients were collected on days 1, 3, 7, 14, and 21 after burn injury, and concentrations of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, and granulocyte-colony stimulating factor (G-CSF) were measured. Burn patients were divided into 3 groups according to burn size (15-30%, 31-50%, >50% total body surface area), and the concentrations of the cytokines were compared between these groups and the control group over 3 weeks. RESULTS: Compared to their levels in controls, IL-6, IL-8, IL-10, TNF-alpha, and G-CSF levels in burn patients were significantly higher during the observation period. Median concentrations of IL-8, IL-10, and G-CSF at each time point increased with burn size, although peak levels and time to peak levels of these cytokines differed from patient to patient. CONCLUSIONS: These findings indicate that IL-6, IL-8, IL-10, TNF-alpha, and G-CSF are important mediators in inflammatory changes after burn injury; however, various factors, including burn size, may influence the concentrations of these cytokines.
Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; Burns/blood/*pathology ; Granulocyte Colony-Stimulating Factor/*blood ; Humans ; Interleukin-10/*blood ; Interleukin-6/*blood ; Interleukin-8/*blood ; Male ; Middle Aged ; Republic of Korea ; Time Factors ; Tumor Necrosis Factor-alpha/*blood ; Young Adult