Usefulness of G-CSF in pediatric high risk cancer patients with fever and neutropenia

Chemotherapy associated febrile neutropenia is an important cause of morbidity and mortality in pediatric patients with cancer. The use of granulocyte-colony stimulating factor (G-CSF) post chemotherapy decreases the risk of infectious complications but its efficacy during the febrile neutropenic episode remains controversial. Thirty five episodes of high-risk febrile neutropenia were randomized into two treatment arms, 18 received antibiotics and G-CSF (group A) and 17 received antibiotics only upon admission (group B). Both groups were comparable in terms of demographic and clinical characteristics. No significant differences between groups were found in duration of hospitalization (mean group A 7 vs group B 8 days), antibiotic treatment (mean 7 vs 8 days), fever (3 vs 2 days), nor of neutropenia (4 vs 3 days). One patient in group A died after RSV infection. Considering these results and a literature review, we propose that G-CSF should not be recommended in children during the course of their febrile neutropenic episode.     

Rapid leukaemic evolution in a cutaneous blastic NK-celllymphoma initially diagnosed as pseudolymphoma

This study was aimed to evaluate the efficacy of G-CSF (Granulocyte colony stimulating factor) administration to 37 patients with neutropenia following intensive combination chemotherapy. The patients were divided into two subgroups including solid tumors given ifosfamide and etoposide combination chemotherapy (IMET subgroup) and acute myeloid leukemia (AML) patients treated with mitoxantrone and cytarabine. Control group consisted of 31 acute myeloid leukemia patients. G-CSF was started on the first day of absolute neutropenia until the absolute neutrophil count was above 1000/mm³ for two consecutive days. G-CSF was found to be effective for early recovery of neutrophil count. Expected response was achieved within 14 days in 91.5% of the courses with a median of fifth day of G-CSF treatment. In conclusion, this study showed the efficacy of G-CSF in early recovery of neutrophil count without any reduction in the incidence of febrile episodes and documented rates of bacterial and fungal infections in patients with acute myeloid leukemia.     

Assessment of the value of treatment with granulocyte colony-stimulating factor in children with acute lymphoblastic leukemia: a randomized clinical trial

Abstract: The present trial was designed to test the effects of G-CSF on the duration of the second phase of induction chemotherapy in children with newly diagnosed acute lymphoblastic leukemia (ALL). A total of 32 patients were assigned randomly to a group that received (14 patients; group A) or a group that did not receive (18 patients; group B) G-CSF (10 g/kg/day subcutaneously and daily) throughout of the second phase of induction therapy. One of 14 (7.1%) patients in group A and 2 of 18 (11.1%) patients in group B completed the course of chemotherapy within the planned time. The median length of this phase was 37 days (range, 29 to 65; mean, 40; SD, 8.6) for patients in group A and 36 days (range, from 29 to 55; mean, 38; SD, 7.4) for those in group B, and the difference was not statistically significant. The number of days during which patients had granulocyte counts of less than 2 × 10⁹/l, the number of febrile episodes of unknown origin, the number of bacterial and fungal infections and the number of days of hospitalization did not differ in a statistically significant manner between the two groups. Our data suggest that G-CSF supportive therapy may be unnecessary in children with neutropenia of short duration, for whom the risk of infection is low.     

Concomitant granulocyte colony-stimulating factor and induction chemoradiotherapy in adult acute lymphoblastic leukemia: a randomized phase III trial

This prospective multicenter study examined whether simultaneous administration of granulocyte colony-stimulating factor (G-CSF; Filgrastim) and induction chemotherapy for adult acute lymphoblastic leukemia (ALL) could prevent treatment-related neutropenia, infections, and resulting treatment delays. Seventy-six patients were randomly assigned to receive either G-CSF (n = 37) or no growth factor (n = 39) in conjunction with a uniform chemotherapy consisting of cyclophosphamide, cytarabine, mercaptopurine, intrathecal methotrexate, and cranial irradiation. The median duration of neutropenia (absolute neutrophil count < 1 x 10(9)/L) during chemotherapy was 8 days in patients receiving C-CSF, compared with 12.5 days in the control group (P < .002). A similar reduction from 11.5 to 7 days was observed in patients with T-ALL receiving additional mediastinal irradiation (P = .13). Infections occurred in 43% and 56% of patients in the G-CSF and control arm, respectively (P = .25); the incidence of nonviral infections was reduced by 50%, from 32 episodes in the control arm to 16 episodes in the G-CSF arm. Prolonged interruptions of chemotherapy administration were less frequent, with delays of 2 weeks or more occurring in only 24% of patients receiving G-CSF as opposed to 46% in the control arm (P = .01). Accordingly, chemotherapy was completed significantly earlier with the use of G-CSF (39 v 44 days, P = .008). With a median follow-up of 20 months, the probability of disease-free survival was 0.45 in the G-CSF group and 0.43 in the control group (P = .34). In conclusion, adult ALL patients appear to benefit by the simultaneous administration of G-CSF with induction chemotherapy because of a significant reduction in the duration of neutropenia, a trend to fewer infections, and a more rapid completion of chemotherapy.     

A double-blind controlled study of granulocyte colony-stimulating factor started two days before induction chemotherapy in refractory acute myeloid leukemia. Kohseisho Leukemia Study Group [see comments]

We conducted a prospective, double-blind controlled study to determine the efficacy of a recombinant granulocyte colony-stimulating factor (G- CSF, 200 microgram/m2) starting daily from 2 days before an induction therapy until neutrophils recovered to above 1,500/microL or until 35 days after the therapy in 58 patients with relapsed or refractory acute myeloid leukemia (AML). Twenty-eight patients in the G-CSF group showed significantly faster recovery of neutrophils (P < .001) than 30 patients in the placebo group. The incidence of febrile episodes and of documented infections was almost the same in both groups. However, among 39 patients who did not show any infectious episodes during the 2- week period after the start of chemotherapy, the incidence of documented infections after the third week tended to be lower in the G- CSF group, but not statistically significantly. There was no evidence that G-CSF stimulated the growth of AML cells in the bone marrow during the 2-day period before the chemotherapy, nor that G-CSF accelerated the regrowth of AML cells during the 5-week period after the therapy. Fifty percent of patients in the G-CSF group and 37% in the placebo group had complete remission (CR). Although the rate was higher in the G-CSF group, the difference was not statistically significant (P = .306). There was no difference between the two groups in event-free survival of all patients and in disease-free survival of patients who had achieved CR.     

High-dose cytarabine-containing chemotherapy with or without granulocyte colony-stimulating factor for children with acute leukemia

We sought to determine the role of granulocyte colony-stimulating factor (G-CSF) as an adjunct therapy in high-dose cytarabine-containing chemotherapy (HD C/T) for children with acute leukemia. Seventeen patients, aged 9 months to 18 years old, 8 ALL and 9 AML, were treated with cytarabine (Ara-C) 1 g/m² q12h for 8 doses with mitoxantrone, idarubicin, VP-16, or asparaginase. A total of 71 courses of HD C/T was given. G-CSF was not used in 14 courses (Group A). Prophylactic G-CSF was given in 57 courses (Group B) as 200 μg/m²/d SC started one day after the completion of HD C/T and continued until the neutrophil recovery was maintained. The incidences of sepsis per course in Group A and Group B were 35.7% (5/14) and 40.4% (23/57), respectively. While 2 patients in Group A died of sepsis or pneumonia, none in Group B died. The mortality and delay in chemotherapy were fewer in Group B (P = 0.037 and 0.0006, respectively, Fisher exact test). There was a shorter average number of days of neutrophil <500/cumm, antibiotic usage, fever, and hospital stay in Group B (11, 8, 5, 17 days in Group B vs. 21, 17, 10, 37 days in Group A; P = 0.0001, log-rank test; 0.0006, 0.0023, 0.0001, Wilcoxon rank sum test, respectively). The incidence of neutropenic fever was lower in Group B, but the difference did not reach statistical significance (P = 0.06, Fisher exact test). We conclude that G-CSF as an adjunct therapy in HD C/T is effective in reducing mortality, days of neutropenia, antibiotic usage, fever, hospital stay, and frequency of delay in chemotherapy. The efficacy of this treatment approach requires further testing in a randomized, controlled trial. Am. J. Hematol. 58:20–23, 1998. © 1998 Wiley-Liss, Inc.     

Prophylactic human granulocyte colony-stimulating factor after induction therapy in pediatric acute myeloid leukemia

Children with acute myelogenous leukemia (AML) have a high risk of infectious complications that might be reduced by prophylactic granulocyte colony-stimulating factor (G-CSF). However, G-CSF could induce AML blast proliferation. The prospective randomized trial AML-BFM 98 investigated the impact of G-CSF on hematopoetic recovery and infectious complications (primary endpoints) and on outcome (secondary endpoint) in children (aged 0-18 years) with de novo AML. Patients with more than 5% blasts in day-15 bone marrow or with FAB M3 were not included. Between 1998 and 2003, 161 children with AML were randomized to receive G-CSF after inductions 1 and 2, whereas 156 patients were assigned to the control group. Time of neutropenia after inductions 1 and 2 was significantly shorter in the G-CSF group (23 vs 18 days and 16 vs 11 days; P=.02 and=.001, respectively). G-CSF did not decrease the incidence of febrile neutropenia (72 and 36 patients vs 78 and 37 patients, respectively), microbiologically documented infections (27 and 25 patients vs 36 and 19 patients, respectively) and infection-associated mortality (5 vs 2 patients). Both groups had similar 5-year event-free survival (EFS; 59%+/-4% vs 58%+/-4%). Since G-CSF does not influence the risk of infectious complications or outcome in children undergoing therapy for AML, one cannot advocate the routine use of G-CSF in this patient group.     

Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study

The role of glycosylated recombinant human granulocyte colony-stimulating factor (G-CSF) in the induction treatment of older adults with acute myeloid leukemia (AML) is still uncertain. In this trial, a total of 722 patients with newly diagnosed AML, median age 68 years, were randomized into 4 treatment arms: (A) no G-CSF; (B) G-CSF during chemotherapy; (C) G-CSF after chemotherapy until day 28 or recovery of polymorphonuclear leukocytes; and (D) G-CSF during and after chemotherapy. The complete remission (CR) rate was 48.9% in group A, 52.2% in group B, 48.3% in group C, and 64.4% in group D. Analysis according to the 2 x 2 factorial design indicated that the CR rate was significantly higher in patients who received G-CSF during chemotherapy (58.3% for groups B + D vs 48.6% for groups A + C; P = .009), whereas no significant difference was observed between groups A + B and C + D (50.6% vs 56.4%, P = .12). In terms of overall survival, no significant differences were observed between the various groups. Patients who received G-CSF after chemotherapy had a shorter time to neutrophil recovery (median, 20 vs 25 days; P < .001) and a shorter hospitalization (mean, 27.2 vs 29.7 days; P < .001). We conclude that although priming with G-CSF can improve the CR rate, the use of G-CSF during and/or after chemotherapy has no effect on the long-term outcome of AML in older patients.     

A prospective study on the epidemiology of febrile episodes during chemotherapy-induced neutropenia in children with cancer or after hemopoietic stem cell transplantation.

BACKGROUND: The purpose of our study was to evaluate the incidence and clinical characteristics of febrile episodes during neutropenia following chemotherapy in children with cancer. PATIENTS AND METHODS: A prospective, 3-year single-center observational study of periods of neutropenia was performed. Epidemiology and clinical diagnoses of febrile episodes occurring during the neutropenic periods were evaluated, taking into consideration different categories of anticancer treatment based on the type of tumor and phase of therapy. RESULTS: A total of 703 febrile episodes were observed during 614 (34%) of 1792 neutropenic periods (34%), for a total of 28,001 days at risk, accounting for a rate of 0.76 episodes per 30 days at risk. The highest proportions of neutropenic periods with primary febrile episodes were observed after autologous hemopoietic stem cell transplantation (58%), aggressive treatment for acute leukemia or non-Hodgkin lymphoma (48%), and allogeneic hemopoietic stem cell transplantation (44%); the lowest proportion (9%) was observed during maintenance chemotherapy for acute leukemia (P<.001). The most frequent clinical diagnosis was fever of unknown origin (in 79% of cases), followed by bacteremia (10%); invasive mycosis was diagnosed in only 2% of cases. CONCLUSIONS: The overall incidence of febrile neutropenia and severe infectious complications in children with cancer is low, with differences according to the aggressiveness of chemotherapy. This fact must be considered when designing clinical trials on the management of infectious complications in children with cancer.     

Successful treatment of neutropenia in T-LGL leukemia (Tγ-lymphocytosis) with granulocyte colony-stimulating factor

Summary Severe neutropenia is a common feature in patients with T-large granular lymphocytic (LGL) leukemia. Neutropenia often causes severe infections and septicemia, thus representing a major cause of morbidity and mortality in this disease. We have treated two outpatients with T-LGL leukemia who had severe neutropenia (neutrophils <0.2×10⁹/l) successfully with G-CSF (5g/kg daily, s.c). After 10 days of treatment the neutrophil count was within the normal range and a severe oral infection healed rapidly. We conclude that G-CSF therapy is able to normalize the neutrophil count in T-LGL leukemia within a few days and that it can be used to treat severe infections in these patients even on an outpatient basis.     

Effect of granulocyte/colony-stimulating factor on the onset of the adult respiratory distress syndrome.

To evaluate the effect of granulocyte/colony-stimulating factor (G-CSF) on the onset of the adult respiratory distress syndrome (ARDS), we investigated whether the incidence of ARDS due to pulmonary infection differed between the G-CSF group which received chemotherapy with G-CSF and historical controls without G-CSF. We evaluated 132 patients with hematological malignancy in complete remission without any main organ dysfunction who had been treated between April 1983 and December 1997. We compared the incidence of ARDS due to pulmonary infection between those who received G-CSF and those who did not. There was no remarkable difference in the number of patients, gender, age, or distribution of primary diseases between the two groups. The intensity of chemotherapy was not considered to significantly differ between the two groups, though the chemotherapy regimens administered differed slightly. In the G-CSF group, the duration of neutropenia was significantly shorter and the frequency of documented infection was significantly decreased. We could not find any relationship between ARDS due to pulmonary infection and any anticancer agent or antibiotics. There was no relationship between the kind of G-CSF and the incidence of ARDS due to pulmonary infection (per chemotherapy session; p > 0.10, per case; p > 0.30, chi2 test). The incidence of ARDS due to pulmonary infection per chemotherapy session was 4.21%, and showed a higher tendency in the G-CSF group (p < 0.100, chi2 test). The incidence of ARDS due to pulmonary infection per case was 25.4% and was significantly higher in the G-CSF group (p < 0.025, chi2 test). The incidence of ARDS due to pulmonary infection was higher in the G-CSF group than in the controls, suggesting that G-CSF promotes the development of ARDS due to pulmonary infection.     

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     

Antibiotic prophylaxis with teicoplanin on alternate days reduces rate of viridans sepsis and febrile neutropenia in pediatric patients with acute myeloid leukemia

Intensive chemotherapy directed against acute myeloid leukemia of childhood is followed by profound neutropenia and high risk for bacterial and fungal infections, including viridans group streptococci as a common cause for gram-positive septicemia. Few retrospective studies have shown the efficacy of various antibiotic prophylactic regimens in children. We retrospectively studied 50 pediatric patients treated on the AML-BFM 2004 protocol between 2005 and 2015 at St. Anna Children’s Hospital and assessed the effect of antibiotic prophylaxis on the frequency of febrile neutropenia and bacterial sepsis. Fifty pediatric patients underwent 199 evaluable chemotherapy cycles. Viridans sepsis occurred after none of 98 cycles with prophylactic administration of teicoplanin/vancomycin in comparison to 12 cases of viridans sepsis among 79 cycles without systemic antibacterial prophylaxis (0 vs. 15 %, p?<?0.0001). In addition, there were significantly fewer episodes of febrile neutropenia in the teicoplanin/vancomycin group (44 % vs. no prophylaxis 82 %, p?<?0.0001). Severity of infection seemed to be worse when no antibiotic prophylaxis had been administered with a higher rate of intensive care unit treatment (0/98, 0 %, vs. 4/79, 5 %, p?=?0.038). So far, no increase of vancomycin-resistant enterococcus isolates in surveillance cultures was noticed. Antibiotic prophylaxis with teicoplanin (or vancomycin) appears safe and feasible and resulted in eradication of viridans sepsis and decreased incidence of febrile neutropenia in pediatric AML patients. The possibility to administer teicoplanin on alternate days on an outpatient basis or at home could contribute to patient’s quality of life and decrease health care costs.     

Comparison of ciprofloxacin with polymyxin B for infection prophylaxis in neutropenic patients with acute non-lymphocytic leukemia

Twenty-four neutropenic patients receiving intensive chemotherapy for acute non-lymphocytic leukemia were studied in a randomized trial comparing ciprofloxacin with polymyxin B for prevention of infections. Both groups (12 patients each group) received amphotericin B for antifungal prophylaxis. 20 febrile episodes occurred in 22 courses of oral prophylactic ciprofloxacin and 22 occurred in 24 courses of oral prophylactic polymyxin B. Patients receiving ciprofloxacin had a mean time to the first infection-related febrile episode of 7.2 days, compared with 4.3 days for the polymyxin B group (p less than 0.01). Patients receiving ciprofloxacin also had fewer days of fever (average 6.5 days versus 9.8 days for the polymyxin B group, p less than 0.02). Duration of administration of parental antibiotics were also shorter in the ciprofloxacin group (p less than 0.001). Although modifications of the empiric antibiotic regimen were required more frequent in patients receiving polymyxin B, this did not reach statistical significance. These results suggest that ciprofloxacin is a more efficacious oral antimicrobial agent than polymyxin B for the prevention of infections in neutropenic patients with acute non-lymphocytic leukemia.     

Granulocytopenia in hospitalized patients: I. Prognostic factors and etiology of fever

The clinical course of 126 hospitalized patients during 192 episodes of granulocytopenia and fever was studied. Fever was a regular accompaniment of granulocytopenia, occurring in 94 per cent of granulocytopenic episodes. The mean duration of granulocytopenia (less than 1,000/mm3) was 18 days, with fever (temperature greater than 38 degrees C) being present during 44 per cent of those days. Fever was present during 69 per cent of days with a granulocyte count less than 10/mm3. A presumed infection was present in 86 of 128 febrile granulocytopenic episodes in adults and in 19 of 64 febrile granulocytopenic episodes in children. A fungal infection was found in 11 patients; a viral infection in 23 patients. Bacteremia occurred during 44 granulocytopenic episodes with 16.8 bacteremias/1,000 days of granulocytopenia in adults and 12.7 bacteremias/1,000 days in children. The mortality was 33 per cent per granulocytopenic episode in adults and only 8 per cent per episode in children.     

Combined administration of alpha-erythropoietin and filgrastim can improve the outcome and cost balance of autologous stem cell transplantation in patients with lymphoproliferative disorders

We compared the use of G-CSF plus EPO in a group of 32 multiple myeloma and lymphoma patients with historical controls receiving G-CSF alone. Haemopoietic reconstitution was significantly faster in patients receiving G-CSF+EPO (group B), with a median time of 10 days to achieve an ANC count >0.5 x 10(9)/l, compared to 11 days in the historical group (A). The median duration of severe neutropenia (ANC count <100/ml) was significantly shorter in group B compared to group A; platelet counts >20 x 10(9) and >50 x 10(9)/l were achieved at days + 13 and + 17, respectively in group B, compared to days + 14 and + 24, respectively, in group A (P = 0.015, 0.002) patients. The transfusion requirement was reduced in group B, with 0 (0-6) RBC units and 1 (0-5) platelet unit transfused in group B vs 2 RBC (0-9) and 2 platelet units (0-8) in group A. Median days of fever, antibiotic therapy and hospital stay were reduced in group B (9.5 days vs 22). The mean cost of autotransplantation per group A patient was 23,988 Euro, compared with 18,394 Euro for a group B patient. Our study suggests that the EPO + G-CSF combination not only accelerates engraftment kinetics, but can also improve the clinical course of ASCT.     

Successful treatment of invasive pulmonary aspergillosis with G-CSF and M-CSF during long-term bone marrow suppression in hypoplastic leukemia

A 52-year-old man was admitted for treatment of hypoplastic leukemia (M 1). After induction chemotherapy with IDR and AraC, the patient developed prolonged febrile neutropenia, and a diagnosis of invasive pulmonary aspergillosis was made. We started administration of AMPH-B and G-CSF, but the patient showed no clinical improvement. M-CSF was added to the regimen, and this led to an increase in the white blood cell count with resolution of pneumonia. It is suggested that administration of M-CSF with antibiotics and G-CSF may be beneficial for treating acute leukemia patients with prolonged febrile neutropenia after intensive chemotherapy.     

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.     

Sustained G-CSF plasma levels following administration of pegfilgrastim fasten neutrophil reconstitution after high-dose chemotherapy and autologous blood stem cell transplantation in patients with multiple myeloma

OBJECTIVE: Pegfilgrastim has shown to decrease the duration of severe neutropenia after conventional chemotherapy, but its use after high-dose chemotherapy and autologous blood stem cell transplantation has not been established yet. Therefore we studied the efficacy and the pharmacokinetic profile of pegfilgrastim in patients with multiple myeloma undergoing high-dose chemotherapy. METHOD: In total, 21 patients received a single subcutaneous injection of 6 mg pegfilgrastim on day +1 after transplantation and pegfilgrastim plasma levels were measured daily by enzyme-linked immunosorbent assay. Clinical outcome was compared with pegfilgrastim levels of 282 plasma samples and data of a historical control group of patients without granulocyte colony-stimulating factor (G-CSF) support. RESULTS: Pegfilgrastim levels showed an inverse correlation (r = -0.68, p < 0.01) with neutrophil counts. Peak levels were reached at day +4 (94 ng/mL; range: 37-205) and were maintained until day +7 (85 ng/mL; range: 35-186). Comparison with the control group without G-CSF support showed that time to neutrophil reconstitution was significantly shorter in the pegfilgrastim group with 10 vs 15 days, respectively (p < 0.001). There was no correlation of pegfilgrastim levels and the duration of neutropenia, although patients with a fivefold increase in neutrophil counts the day after pegfilgrastim administration had a significantly shorter median duration of neutropenia in comparison to patients who were less susceptible to G-CSF stimulation (5 vs 7 days, p < 0.01). CONCLUSION: Neutrophil reconstitution after high-dose chemotherapy could be accelerated by the use of pegfilgrastim in patients with myeloma. Responsiveness of neutrophils to pegfilgrastim before neutropenia was correlated with faster neutrophil reconstitution, whereas G-CSF levels had no impact on neutrophil recovery.     

Individually determined dosing of filgrastim after autologous peripheral stem cell transplantation in patients with malignant lymphoma--results of a prospective multicentre controlled trial

OBJECTIVES: To explore the safety and effectiveness of the individually determined application granulocyte-colony stimulating factor (G-CSF) after autologous peripheral blood stem cell transplantation (ASCT). METHODS: The administration of G-CSF from day +5 (arm A) was compared in a randomised, controlled trial with delayed, individually determined administration (G-CSF started when WBC >or= 0.5 x 10(9)/L and ANC >or= 0.1 x 10(9)/L or at day +10; arm B), and with placebo (arm C). RESULTS: One hundred and six patients, median age 45 (range 21-64), all with malignant lymphoma treated with BEAM chemotherapy were analysed. A significant difference in the time to neutrophil engraftment and in the duration of neutropenia <0.5 x 10(9)/L and <1.0 x 10(9)/L was observed between the arms (P = 0.04-<0.0001) with a 1-d prolongation of the median durations in arm B in comparison with arm A but a 2-4-d prolongation in the placebo arm C in comparison with arm B. The median number and range of days to neutrophil engraftment >0.5 x 10(9)/L after graft re-infusion was 10 (9-14) in arm A; 11 (9-19) in arm B; and 14 (10-30) in arm C (P < 0.0001). Engraftment of platelets to >20 x 10(9)/L and >50 x 10(9)/L was significantly delayed in the arms using G-CSF in comparison with placebo (P = 0.04-0.002) without any increase in bleeding or in transfusion requirement. There was no difference in the incidence and duration of transplant-related complications and their treatment between the arms. CONCLUSIONS: Our study has confirmed the safety of individually determined administration of G-CSF. The optimal timing of G-CSF application after ASCT in patients with good-quality grafts is shortly before expected spontaneous engraftment.