Clinical studies of recombinant human granulocyte colony-stimulating factor in elderly patients with malignant lymphoma]

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was given in combination with chemotherapy in elderly patients (greater than or equal to 65 years old) with malignant lymphoma, and the therapeutic efficacy and the incidence of side effects were determined. The subjects consisted of 5 males and 8 females with a median age of 74 years. One patient had Hodgkin's disease and 12 had non-Hodgkin's lymphoma. Regarding lymphoma stage, 2 were in stage II, 3 were in stage III, and 8 were in stage IV. The chemotherapy used was COP-BLAM in 8 patients, COP-BLAM III in 2, IMV-triple P in 2, and ACVP-16 in 1. Treatment with rhG-CSF (1.5 micrograms/kg/day) was commenced during or after the 2nd course of chemotherapy when the neutrophil count dropped to greater than or equal to 1,000/microliters, and was continued until the recovery of either the neutrophil or leukocyte count to 10,000/microliters or 20,000/microliters, respectively. The neutrophil nadir in the non-G-CSF group was 367.3 +/- 231.6/microliters. In the G-CSF group it was 754.6 +/- 116.4/microliters for the second course, with the difference between the 2 groups being significant (p less than or equal to 0.05). Also, the following time periods were significantly shorter in the G-CSF group than the non-G-CSF group: 1) the duration of a neutrophil count less than 1,000/microliters, 2) the duration of fever (greater than or equal to 37.5 degrees C), and 3) the time to recovery from the neutrophil nadir.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of recombinant human granulocyte colony-stimulating factor on neutropenia in patients with AIDS.

The efficacy of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutropenia was evaluated in 14 patients with AIDS and AIDS-related complex (ARC). In all patients, including 11 neutropenic patients, 100 or 200 micrograms/m2 of rhG-CSF significantly increased the neutrophil counts. The response was greater in patients with higher neutrophil counts before the treatment, and was also dose-dependent. Although the effect seemed to be less potent, the agent also increased the neutrophil counts even when zidovudine (azidothymidine, AZT) and other myelosuppressive antiviral agents were administered simultaneously. These observations indicate that rhG-CSF may be beneficial in preventing and treating some secondary infections, and will make it easier to continue therapy with antiviral agents in patients with AIDS or ARC.     

A successful case of congenital agranulocytosis treated with recombinant human granulocyte colony-stimulating factor]

A 1-month-old girl was admitted because of staphylococcal cellulitis of the buttock and the shoulder, and peripheral agranulocytosis. CBC on admission showed 10,100/microliters of WBC with 1% mature neutrophils, 5% monocytes, 6% eosinophils, 2% basophils and 86% lymphocytes. Bone marrow aspiration revealed maturation arrest of neutrophil precursors at the level of myelocyte. We treated the patient with subcutaneous rhG-CSF (Kirin-Amgen, Tokyo) for sequential 7-day course at the starting dose of 3 micrograms/kg, and increased weekly. The dose was escalated at the level of 18 micrograms/kg for 2 weeks subcutaneously, 8 days after effective dose of 18 micrograms/kg, the absolute neutrophil counts more than 1,000/microliters was attained, and bone marrow aspiration showed an increase of neutrophil precursors beyond the myelocyte level with maturation. Our case proved that both WBC and absolute neutrophil counts were increased parallel with the dose escalation of rhG-CSF. Shortly after the cessation of rhG-CSF, WBC and absolute neutrophil counts were decreased. No side effect was detected except for mild splenomegaly which was resolved after cessation of rhG-CSF. In methylcellulose culture with PHA-LCM, marrow cell of patient produced normal number of CFU-GM, and myeloid precursors could proliferate and differentiate to normal polymorphonuclear neutrophils, but rhG-CSF produced only small number of CFU-GM. Our case confirms that rhG-CSF is a new approach to control the life-threatening infection of congenital agranulocytosis.     

In vivo activation of human neutrophil functions by administration of recombinant human granulocyte colony-stimulating factor in patients with malignant lymphoma

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered (50 to 800 micrograms/m2) once daily as a half-hour intravenous (IV) infusion for 14 days to seven patients with malignant lymphoma. In all patients, administration of rhG-CSF not only ameliorated the decrease in absolute neutrophil count after the cytotoxic chemotherapy but also enhanced superoxide (O2-) release in neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP). The priming effect of rhG-CSF on neutrophil O2- release was rapid (evident within 6.5 hours) and sustained at least for 24 hours after a single IV administration of rhG-CSF. The responsiveness to further in vitro challenge of rhG-CSF was lost or reduced in neutrophils isolated after rhG-CSF treatment, indicating that neutrophils already primed in vivo by rhG-CSF are desensitized to this factor. In contrast to the results obtained with FMLP, when phorbol myristate acetate (PMA) was used as stimulus, no consistent enhancement of O2- release was observed, suggesting that rhG-CSF modulates the signal transduction pathways linked to FMLP receptors rather than increases the components of the O2- producing enzyme complexes. Administration of rhG-CSF also rapidly (evident within 15 minutes) caused an increase in expression of neutrophil C3bi-receptors that was sustained for at least 24 hours after a single IV administration of rhG- CSF. Pharmacokinetic study of rhG-CSF showed a half-life (t1/2) of 114 min. These findings show that rhG-CSF is a potent activator for neutrophil functions both in vivo and in vitro.     

Kinetics of circulating hematopoietic stem cells following chemotherapy in patients with hematopoietic malignancies]

The number of circulating hematopoietic progenitor cells was determined during 47 courses of chemotherapy in 23 patients with hematopoietic malignancies. rhG-CSF was given subcutaneously to 14 patients to rescue chemotherapy-induced neutropenia following 22 courses of chemotherapy. The mean numbers of CFU-GM in patients with malignant lymphoma (ML), acute leukemia (AL) and myeloma (MM) were 56.0 +/- 58.8 (mean +/- SD), 46.7 +/- 66.0 and 11.0 +/- 11.1 CFU-GM/ml, respectively. The number of CFU-GM in MM was significantly less than in normal subjects (51.2 +/- 30.6 CFU-GM/ml). The number of CFU-GM in PB in all patients began to rise between 2 days before and 8 days after nadir of WBC count, and then reached the peak at the subsequent 5 days. The peak values of CFU-GM in ML, AL and MM were 711.3 +/- 974.7, 660.0 +/- 374.7 and 403.6 +/- 232.5 CFU-GM/ml, respectively, but there was no statistical difference among them. When ML patients were treated with rhG-CSF, the CFU-GM peak values increased as much as 5.5-folds compared with those following chemotherapy only. However, neither the period from nadir to start of increase in the CFU-GM count nor the time of the CFU-GM peak showed any significant change. These results indicate that the administration of rhG-CSF makes it possible to increase the number of circulating progenitor cells. It appears possible in most of the patients with hematopoietic malignancies to harvest the sufficient number of progenitor cells which are necessary for autologous blood stem cell transplantation.     

Leucocyte transfusions from rhG-CSF or prednisolone stimulated donors for treatment of severe infections in immunocompromised neutropenic patients

Sepsis in profound neutropenia after chemotherapy is associated with high mortality despite appropriate antibacterial or antifungal treatment. In a prospective phase I/II study we evaluated the feasability and efficacy of leucocyte transfusions (LT) in patients with malignancies or haematological disorders who were suffering from severe bacterial or fungal infection during therapy-related bone marrow aplasia. 30 patients with severe neutropenia and clinical signs of life-threatening sepsis not responding to adequate treatment, received LT from rhG-CSF-stimulated family donors or from prednisolone-primed volunteers. A total of 301 LT were administered. The median number of LT per patient was seven (range three to 65), the median duration of LT treatment was 8 d (range 2-35). The white cell count (WBC), absolute neutrophil count (ANC) and lymphocyte count of the concentrates from rhG-CSF-stimulated donors were significantly higher than those from prednisolone-primed volunteers (P = 0.0001). Despite the critical condition of the patients, LT were generally well tolerated. Only 39 (12.9%) LT were associated with adverse reactions. The transfusion of leucocytes collected by continuous flow leukapheresis from both rhG-CSF and prednisolone stimulated donors resulted in a measurable increment of the peripheral leucocyte and ANC counts in our patients. On day 100 after the first LT, 20/30 patients were alive with complete clearance of the infection.     

Clinical effects of recombinant human granulocyte colony-stimulating factor in leukemia patients: a phase I/II study

A phase I/II study of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in 24 leukemia patients was conducted at our institute. Recombinant human G-CSF (50-200 micrograms/m2/day) was administered i.v. In seven allogeneic bone marrow transplantation (BMT) recipients, treatment with rhG-CSF was started 5 days after BMT. Neutrophils began to increase within 3 days after the start of rhG-CSF administration in five of seven patients. The mean duration necessary for recovery of neutrophils to greater than 500/microliters was 11.3 days after BMT with rhG-CSF; 26.8 days is the figure for recovery without rhG-CSF from Japanese historical data. In seven out of eight patients who received rhG-CSF administration after the first remission-induction chemotherapy, the neutrophil counts increased from less than 300/microliters to greater than 4000/microliters within 10 days. Blasts did not increase in all patients including four acute nonlymphocytic leukemia (ANLL) patients. Severe infections such as septicemia and pneumonia, which were unable to be controlled by antibiotics only, were successfully treated with rhG-CSF and antibiotics. rhG-CSF either stimulated or inhibited myeloid leukemic cells in some refractory cases. Mild bone pain occurred in one patient while receiving rhG-CSF i.v. rhG-CSF seems to have the ability to shorten the period of neutropenia, prevent infections after allogeneic BMT and remission-induction chemotherapy for acute leukemia, and support therapy for infections.     

Treatment of idiopathic neutropenia in the elderly with recombinant human granulocyte colony-stimulating factor.

We administered recombinant human granulocyte colony-stimulating factor (rhG-CSF) intravenously for 2 weeks to 2 elderly patients with severe neutropenia. The absolute neutrophil count (ANC) recovered promptly after the initiation of rhG-CSF therapy and reached a peak (greater than 10 x 10(9)/l) on the 13th day. The ANC fell rapidly after rhG-CSF was discontinued, but it remained within the normal range after therapy. There were no side effects during the entire course of treatment. Therefore, rhG-CSF seems to be a most beneficial treatment in elderly patients with severe neutropenia.     

Neutrophil kinetics shortly after initial administration of recombinant human granulocyte colony-stimulating factor: neutrophil alkaline phosphatase activity as an endogenous marker.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered (1.5 micrograms/kg body weight) subcutaneously once daily for 5 to 9 days to 5 patients with malignant lymphoma. In all patients, initial administration of rhG-CSF induced a rapid fall in the neutrophil count within 30 minutes, followed by a recovery and an increase in the neutrophil count within 150 min. A rapid fall in the neutrophil count was accompanied by increased expression of neutrophil C3bi-receptors, and neutrophils left in the circulation had lower activity of neutrophil alkaline phosphatase (NAP) and phagocytosis. A decrease in the NAP scores observed at 30 min reflected a preferential decrease of neutrophils with high NAP activity. A recovery and an increase in the neutrophil count were accompanied by a further decrease of NAP scores, which was caused by a preferential increase of neutrophils with lower NAP activity. The NAP scores of mature neutrophils from peripheral blood were not affected by in vitro treatment of cells with rhG-CSF for up to 150 min at 37 degrees C. These findings and the previous observations that neutrophils in the circulating and marginal pools have high NAP activity and neutrophils in the bone marrow pool have low NAP activity taken together suggest that, following initial administration of rhG-CSF, functionally active neutrophils leave the bloodstream preferentially, which is primarily followed by an influx of neutrophils from the bone marrow, but not by demargination of sequestered neutrophils.     

Efficacy of recombinant human granulocyte colony-stimulating factor in a murine model of pneumococcal pneumonia: effects of lung inflammation and timing of treatment

The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in a murine model of pneumococcal pneumonia was examined. Intranasal inoculations were 10(7) cfu/mouse (high inoculum) and 5 x 10(4) cfu/mouse (low inoculum) of Streptococcus pneumoniae, which induced severe or mild lung inflammation, respectively. With the low inoculum, rhG-CSF significantly improved survival when initiated 24 h or 10 min before, but not when initiated 24 h after, infection. Pretreatment with rhG-CSF significantly increased myeloperoxidase (MPO) activity in lungs 8 h after the infection and increased circulating neutrophil count 24, 48, and 72 h after infection. In contrast, rhG-CSF did not improve survival of animals infected with the high inoculum and did not increase MPO activity or neutrophil count in blood over those of sham-treated controls. These data strongly suggest that the severe inflammatory response typically observed in pneumococcal pneumonia recruits a maximum number of neutrophils in the lungs and thus masks the beneficial effect of rhG-CSF.     

Treatment of aplastic anemia in children with recombinant human granulocyte colony-stimulating factor

Twenty children (aged 1 to 17 years) with severe or moderate aplastic anemia were treated with recombinant human granulocyte colony- stimulating factor (rhG-CSF) at a dose of 400 micrograms/m2 per day administered as a 30-minute intravenous (IV) infusion daily for 2 weeks. This treatment increased the neutrophil counts (2.7- to 28.0- fold) in 12 of the 20 patients. Increasing doses (800 or 1,200 micrograms/m2 per day) were administered to five patients who had not responded to the initial dose, and three showed an increase in neutrophil count. Differential counts of bone marrow (BM) aspirates showed an increase in the myeloid/erythroid ratio. The response was transient, however, and the neutrophil count returned to baseline within 2 to 10 days of discontinuing treatment. No severe toxicity attributable to rhG-CSF was observed. The results suggest that this agent is effective in stimulating granulopoiesis in children with aplastic anemia. Our study also indicates that rhG-CSF will be particularly useful in managing patients with aplastic anemia complicated by bacterial or fungal infection.     

Detecting of the minimal residual disease contaminated in peripheral blood stem cell transplantation in the B-cell malignant lymphoma patients.

For sufficient collection of hemopoietic stem cells from peripheral blood for autologous peripheral blood stem cell transplantation (PBSCT), four patients with B-cell-type non-Hodgkin lymphoma (B-NHL) were examined for the appearance of circulating hemopoietic progenitors in blood (PSC) during the hemopoietic recovery phase following marrow ablative therapy in combination with or without administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF). Each patient received only chemotherapy in the first course, and rhG-CSF (1 microgram/kg/day) was administered for 14 consecutive days from the last day of the second chemotherapy. In the second chemotherapy course with rhG-CSF administration, white blood cell (WBC) counts demonstrated two peaks, and the appearance of granulocyte-macrophage precursor cells (CFU-GM) in blood at the maximum level was coincident with the second peak of WBC elevation. Erythroid precursor cells (BFU-E) were also detectable in blood after chemotherapy but the peak level was not enhanced by the use of rhG-CSF. To determine whether the minimal residual disease (MRD) cells were contaminated in PSC corrected from blood, kappa-lambda imaging (KLI) analysis was performed to detect the malignant B-cell population (mBp) before and after chemotherapy. No mBp was found in two of four patients in blood, although three of them were involved with mBp in bone marrow. The presence of mBp was detected in two patients both before and after chemotherapy, even though these cells were hardly detected morphologically, suggesting the necessity of judging for the incidence of contamination of MRD cells when collecting PSCs.     

重组人粒细胞—集落刺激因子预防肺癌化部期感染的效果

目的 总结重组人粒细胞－集落刺激因子（ｒｈＧ－ＣＳＦ）预防肺癌化疗期感染的效果。方法 回顾分析１６３例（３０８例次）肺癌患化疗期辅用或不同ｒｈＧ－ＣＳＦ中性粒细胞恢复和感染情况。结果 化疗期用ｒｈＧ－ＣＳＦ患（Ｇ－ＣＳＦ组）感染率（５４／２１７，２５％）明显低于非Ｇ－ＣＳＦ期（５１／９１，５６％）（Ｐ〈０．００５）；Ｇ－ＣＳＦ组化疗期中性粒细胞减少的发生率明显低于非Ｇ－ＣＳＦ组（Ｐ〈０．００５     

Rapid engraftment by peripheral blood progenitor cells mobilized by recombinant human stem cell factor and recombinant human granulocyte colony-stimulating factor in nonhuman primates

We have previously shown that administration of low-dose recombinant human stem cell factor (rhSCF) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) to baboons mobilizes greater numbers of progenitor cells in the blood than does administration of rhG-CSF alone. The purpose of the present study was to determine whether marrow repopulating cells are present in the blood of nonhuman primates administered low-dose rhSCF plus rhG-CSF, and if present, whether these cells engraft lethally irradiated recipients as rapidly as blood cells mobilized by treatment with rhG-CSF alone. One group of baboons was administered low-dose rhSCF (25 micrograms/kg/d) plus rhG- CSF (100 micrograms/kg/d) while a second group received rhG-CSF alone (100 micrograms/kg/d). Each animal underwent a single 2-hour leukapheresis occurring the day when the number of progenitor cells per volume of blood was maximal. For baboons administered low-dose rhSCF plus rhG-CSF, the leukapheresis products contained 1.8-fold more mononuclear cells and 14.0-fold more progenitor cells compared to the leukapheresis products from animals treated with rhG-CSF alone. All animals successfully engrafted after transplantation of cryopreserved autologous blood cells. In animals transplanted with low-dose rhSCF plus rhG-CSF mobilized blood cells, we observed a time to a platelet count of > 20,000 was 8 days +/- 0, to a white blood cell count (WBC) of > 1,000 was 11 +/- 1 days, and to an absolute neutrophil count (ANC) of > 500 was 12 +/- 1 days. These results compared with 42 +/- 12, 16 +/- 1, and 24 +/- 4 days to achieve platelets > 20,000, WBC > 1,000, and ANC > 500, respectively, for baboons transplanted with rhG-CSF mobilized blood cells. Animals transplanted with low-dose rhSCF plus rhG-CSF mobilized blood cells had blood counts equivalent to pretransplant values within 3 weeks after transplant. The results suggest that the combination of low-dose rhSCF plus rhG-CSF mobilizes greater numbers of progenitor cells that can be collected by leukapheresis than does rhG-CSF alone, that blood cells mobilized by low-dose rhSCF plus rhG-CSF contain marrow repopulating cells, and finally that using a single 2-hour leukapheresis to collect cells, the blood cells mobilized by low-dose rhSCF plus rhG-CSF engraft lethally irradiated recipients more rapidly than do blood cells mobilized by rhG- CSF alone.     

Felty's syndrome treated with rhG-CSF associated with flare of arthritis and skin rash

Summary A patient with Felty's syndrome and rheumatoid arthritis was treated with recombinant granulocyte stimulating factor rhG-CSF (Neupogen) in view of severe neutropenia. He had a prompt rise in his neutrophil count and associated with this a severe flare of his arthritis and a skin rash. rhG-CSF was stopped, his neutrophil count fell rapidly and his symptoms resolved. rhG-CSF and the resulting rise in neutrophil count may be associated with flare of autoimmune disease in susceptible individuals.     

The association of total and differential white blood cell count with metabolic syndrome in type 2 diabetic patients

AIMS: We investigated the relation between total and differential white blood cell (WBC) count and metabolic syndrome (MS) in type 2 diabetic patients. METHODS: Eight-hundred and twenty-two patients (males 430, females 392, BMI 25.4+/-3.2 kg/m2, duration of diabetes 5.7+/-6.8 years) were enrolled in this study. We measured total WBC count and differential count, anthropometry, blood pressure, fasting glucose, insulin and lipid profiles. RESULTS: The number of components of MS and prevalence of MS were increased from 1st quartile to 4th quartile of WBC count. Total WBC, neutrophil, lymphocyte, monocyte and eosinophil counts were increased with the increase of number of components of MS except basophil count. Total WBC, neutrophil, lymphocyte, monocyte and eosinophil counts were higher in the patients with MS features than those without MS features. WBC count was positively correlated with waist circumference (gamma=0.134), systolic blood pressure (gamma=0.082), diastolic blood pressure (gamma=0.083), triglyceride (gamma=0.241), insulin (gamma=0.222), and HOMA-IR (gamma=0.225), and negatively with HDL cholesterol (gamma=-0.146) (p<0.05, respectively). CONCLUSIONS: Chronic inflammation, as indicated by a higher WBC count, may be related with the increased number of components of MS in type 2 diabetic patients.     

Changes in neutrophil counts and functions after the administration of recombinant human granulocyte colony-stimulating factor in a patient with chronic idiopathic neutropenia]

The cause of chronic idiopathic neutropenia (CIN) is unknown. Recently recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been purified. Many studies of effects of rhG-CSF on the patients with neutropenia have been undertaken. We examined changes in neutrophil counts and functions after the administration of rhG-CSF in a patient with CIN. Six hours after the intravenous administration of 40 micrograms of rhG-CSF, neutrophil counts were raised from 90 to 1570/microliters, and the increased neutrophils functioned normally; chemotaxis, phagocytosis and O2(-) generation. It is suggested that rhG-CSF is beneficial for the treatment of infection in patients with CIN.     

Treatment of severe neutropenia due to Felty's syndrome or systemic lupus erythematosus with granulocyte colony-stimulating factor.

OBJECTIVES: To examine the efficacy and safety of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for the treatment of severe neutropenia due to Felty's syndrome (FS) or systemic lupus erythematosus (SLE). METHODS: Eight patients with absolute neutrophil counts (ANC) below 1,000/microL attributable to FS (n = 4) or SLE (n = 4) were treated with rhG-CSF. The hematologic and clinical response as well as side effects were recorded. In addition, reports on the use of rhG-CSF/rhGM-CSF in FS and SLE retrieved from the English language literature were analyzed. RESULTS: RhG-CSF effectively corrected neutropenia due to FS and SLE in seven of the current eight patients. In 54 of 55 FS and SLE patients retrieved from the literature, G-CSF or GM-CSF, respectively, proved to be effective at elevating the neutrophil count, which was often associated with improvement of infectious complications. The neutrophil count often declined again when growth factor treatment was stopped but generally stabilized at a level that exceeded the pretreatment count. Side effects included rare cases of thrombocytopenia, arthralgias, and development of cutaneous leukocytoclastic vasculitis. Side effects were dose dependent and resolved when treatment was discontinued. One of our own patients and 17 previously reported patients continued to benefit from long-term administration of rhG-CSF over periods of more than 40 months. CONCLUSIONS: RhG-CSF is an effective and generally well-tolerated treatment for neutropenia due to FS or SLE. Exacerbation of the underlying rheumatic condition due to G-CSF appears to be rare if G-CSF is administered at the lowest dose effective at elevating the ANC above 1,000/microL.     

Clinical significance of recombinant human granulocyte colony-stimulating factor (rG-CSF) in the chemotherapy of patients with malignant lymphoma]

We examined the effects of recombinant human granulocyte colony-stimulating factor (rG-CSF) on neutropenia induced by chemotherapy in 10 patients with non-Hodgkin's lymphoma (NHL). The numbers of peripheral blood hematopoietic progenitors were also evaluated before and after administration of rG-CSF. Six patients received an administration of 2 micrograms/kg/body weight of rG-CSF subcutaneously for 14 days after 2nd chemotherapy. Four patients received intravenous infusion of rG-CSF (300 micrograms/body/day) for 4 days from nadir state after chemotherapy. Administration of rG-CSF from the termination of chemotherapy, markedly shortend the period of bone marrow hypoplasia induced by chemotherapy. On the other hand, administration of rhG-CSF from nadir state after chemotherapy have accelerated the recovery of neutrophil counts. In addition, this type of therapy induced 26 to 60 folds increase of peripheral blood hematopoietic progenitors. These results demonstrate the validity of administration of rhG-CSF not only in the chemotherapy of NHL, but also in peripheral blood stem cell transplantation (PBSCT).     

Mobilization of peripheral blood progenitor cells in patients with breast cancer: a prospective randomized trial comparing rhG-CSF with the combination of rhG-CSF plus rhEpo after VIP-E chemotherapy.

Peripheral blood progenitor cells (PBPC) can be mobilized by chemotherapy, cytokines, or the combination of both. Recently, data from two non-randomized studies were published, showing an advantage for a combination of rhG-CSF plus rhEpo compared to rhG-CSF alone in mobilization of PBPC. To address this question we initiated a prospective, randomized trial in patients with breast cancer. Thirty (28 female, two male) of 32 randomized patients were evaluable. After primary surgery, therapy consisted of two cycles of VIP-E chemotherapy followed by high-dose (HD) chemotherapy with VIC. Mobilization and harvest of PBPC followed cycle 2. Group A received 5 microg rhG-CSF/kg body weight (bw) plus 150 IU rhEpo/kg bw. Group B was treated with 5 microg rhG-CSF/kg bw from dl until end of harvest. In the peripheral blood CD34+ cells as well as colony-forming units (CFU) started to rise on d8 with a peak on d10, followed by a decrease. No significant differences were observed between the groups. Furthermore, there was no significant difference with regard to MNC, CD34+ cells BFU-E and CFU-GM in apheresis products. Transplantation of > 1 x 10(6) CD34+ cells/kg bw after HD chemotherapy resulted in normal hematological recovery of all patients. No differences were observed in time to neutrophil or platelet recovery and need for blood product support. In this study addition of rhEpo to our standard mobilization chemotherapy did not result in improved mobilization of PBPC or in clinical benefits after HD chemotherapy.