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Biomedical subjects

C R Pinkerton

Publications and source records attributed to C R Pinkerton.

At least 55 records · Page 3Linked to original sources
PubMed1998

A limited role for VEEP (vincristine, etoposide, epirubicin, prednisolone) chemotherapy in childhood Hodgkin's disease.

The VEEP regimen (vincristine, etoposide, epirubicin, prednisolone), with or without involved field radiotherapy, has been shown to be an effective treatment in adult Hodgkin's disease. In an attempt to avoid the late sequelae of both alkylating agents and radiotherapy this regimen has been studied in a series of 54 children and young adults. Early analysis suggested that the relapse rate was higher with VEEP than with standard alkylating agent-based regimens. Sufficient follow-up has now been achieved to evaluate the likelihood of sustained remission following second-line treatment and therefore the overall long term survival with this treatment approach. The 5-year Overall Survival (OS) and 5-year Progression Free Survival (PFS) for patients with stage I-III disease was 93% and 82% respectively. However, the 5-year OS and PFS for stage IV patients was only 44% and 50%, respectively. Of 13 patients who were initial treatment failures on VEEP, 7 of whom had advanced disease, only 6 were salvaged with second-line therapy. 8 of 33 who attained a complete response (CR) relapsed and there were 2 relapses in those achieving a partial response (PR) (n = 8). All those relapsing from CR/PR were salvaged by second-line alkylating agent chemotherapy +/- radiotherapy, +/- high dose chemotherapy. In conclusion, patients with stage I-IIIA, non-bulky disease, the moderately high relapse rate did not adversely affect the overall high cure rate, although VEEP failures were subjected to a high total treatment burden. VEEP alone is inadequate in patients with stage IV disease, bulky mediastinal disease in/or those with B symptoms in whom there is a high primary failure rate and relatively poor results with second line therapy.

Adolescent↗
PubMed1998

Improved cure rate in children with B-cell acute lymphoblastic leukaemia (B-ALL) and stage IV B-cell non-Hodgkin's lymphoma (B-NHL)--results of the UKCCSG 9003 protocol.

From June 1990 to February 1996, 35 patients with B-cell acute lymphoblastic leukaemia (B-ALL) 13 of whom had CNS disease and 28 patients with stage IV B-cell non-Hodgkin's lymphoma (B-NHL) 22 of whom had CNS involvement were treated with a short, intensive multiagent chemotherapy regimen (UKCCSG 9003 protocol) based on the French LMB 86 regimen. Fifty-five were boys. The age range was 11 months to 16.5 years (median 8.4 years). Chemotherapy included cyclophosphamide, vincristine, daunorubicin, high-dose methotrexate (COPADM) and etoposide/high-dose cytarabine (CYVE) with frequent intrathecal (i.t.) triple therapy (methotrexate, cytarabine and hydrocortisone). Cranial irradiation (24 Gy in 15 fractions) was recommended in patients with overt CNS disease. One patient with Wiskott-Aldrich syndrome was withdrawn after entry and has been excluded from the analysis. Ten patients (16%) have relapsed (CNS, four; BM, two; combined CNS and BM, three; and jaw, one) 4-11 months after diagnosis and two patients never achieved complete remission (CR). All have died. In seven of the patients who relapsed, treatment had been modified or delayed because of poor clinical condition. Seven patients (11%) died of toxicity 11 days to 4 months after diagnosis. The cause of death was sepsis (n = 5) or sepsis with renal failure (n = 2). With a median follow-up of 3.1 years from diagnosis (range 9 months to 6.3 years), 43 patients (69%) survive in CR. This study confirms the effectiveness of this regimen with regard to the relapse rate (16%), although the rate of toxic death is of concern.

Adolescent↗
PubMed1998

High-dose cyclosporin with etoposide--toxicity and pharmacokinetic interaction in children with solid tumours.

The tolerability, anti-tumour activity and pharmacokinetic interaction of high-dose intravenous cyclosporin combined with intravenous etoposide was evaluated in children. Eighteen patients with recurrent or refractory tumours, all of whom had previously received etoposide, were treated with a combination of high-dose cyclosporin and etoposide. In 13, cyclosporin was given as a continuous infusion (15 mg kg(-1) per 24 h for 60 h) and in five a short 3-hour infusion of 30 mg kg(-1) day(-1) on three consecutive days. Pharmacokinetic profiles of etoposide were determined with and without cyclosporin. Cyclosporin levels ranged from 1359 to 4835 ng ml(-1) and cyclosporin increased the median area under the concentration time for etoposide curve from 7.2 to 12.5 mg ml(-1) min. The major toxicity was acute with varying forms of hypersensitivity reactions. In four cases this was severe. Hyperbilirubinaemia was present in 25 of 32 courses but was of short duration. In 14 courses, creatinine and/or urea was elevated, but was also transient. Significant hypertension was seen in six courses. Four of 17 patients evaluable for response obtained a partial response and one showed stable disease. It is concluded that in children given the combination of high-dose cyclosporin and etoposide, the etoposide dose should be halved in order to achieve an area under the drug concentration-time curve similar to that with etoposide alone. A continuous infusion schedule of cyclosporin is better tolerated during the period of administration but is associated with similar hepatic and renal dysfunction to a short schedule. The 24% response rate in children who had previously received etoposide suggests that this may be an effective method of enhancing drug sensitivity and further phase II evaluation is justified.

Adolescent↗
PubMed1998

Phase I study of temozolomide in paediatric patients with advanced cancer. United Kingdom Children's Cancer Study Group.

A phase I study of temozolomide administered orally once a day, on 5 consecutive days, between 500 and 1200 mg m(-2) per 28-day cycle was performed. Children were stratified according to prior craniospinal irradiation or nitrosourea therapy. Sixteen of 20 patients who had not received prior craniospinal irradiation or nitrosourea therapy were evaluable. Myelosuppression was dose limiting, with Common Toxicity Criteria (CTC) grade 4 thrombocytopenia occurring in one of six patients receiving 1000 mg m(-2) per cycle, and two of four patients treated at 1200 mg m(-2) per cycle. Therefore, the maximum-tolerated dose (MTD) was 1000 mg m(-2) per cycle. The MTD was not defined for children with prior craniospinal irradiation because of poor recruitment. Plasma pharmacokinetic analyses showed temozolomide to be rapidly absorbed and eliminated, with linear increases in peak plasma concentrations and systemic exposure with increasing dose. Responses (CR and PR) were seen in two out of five patients with high-grade astrocytomas, and one patient had stable disease. One of ten patients with diffuse intrinsic brain stem glioma achieved a long-term partial response, and a further two patients had stable disease. Therefore, the dose recommended for phase II studies in patients who have not received prior craniospinal irradiation or nitrosoureas is 1000 mg m(-2) per cycle. Further evaluation in diffuse intrinsic brain stem gliomas and other high-grade astrocytomas is warranted.

Adolescent↗
PubMed1998

Detection of minimal residual disease in B-lineage acute lymphoblastic leukaemia by quantitative flow cytometry.

The clinical significance of detecting minimal residual disease (MRD) in B-lineage acute lymphoblastic leukaemia (ALL) was evaluated by quantitative flow cytometry using a combination of TdT with CD10 and CD19. 53 patients with B-cell precursor ALL were followed during and after completion of treatment (median follow-up 23 months). Nine patients relapsed and MRD had been detected in six of them, 5-15 weeks before relapse despite morphological complete remission. 43 patients remain in clinical remission and in none of these was MRD detected. Disease-free survival based on the detection of MRD by flow cytometry showed a statistically significant difference between both groups (P<0.0001). The absence of MRD correlates with a low relapse rate, whereas the presence of MRD predicted early relapse. This study has shown that flow cytometry can improve the morphologic assessment of bone marrow (BM) remission status in B-lineage ALL. The finding of < 5% blasts in BM aspirates did not correlate with 'true' remission in a proportion of cases as residual leukaemic blasts were detected by flow cytometry in nine samples from six patients. On the other hand, the presence of > 5% blasts assessed by morphology was not necessarily a feature of relapse in five patients as these cells were shown to have a phenotype identical to normal TdT-negative B-cell precursors. Quantitative flow cytometry was more informative than conventional morphology to assess remission status and showed a strong correlation with clinical outcome. This methodology is useful to define MRD in the majority of patients with B-lineage ALL and should be tested in prospective clinical trials.

Adult↗
PubMed1998

Conservative management of follicular non-Hodgkin's lymphoma in childhood.

Among 447 children with non-Hodgkin's lymphoma (NHL) on the childhood U.K. registry, seven children with follicular (NHL) were identified. Four were male and their age ranged from 4.25 to 13.5 years (median 7.5); all had localized disease, Murphy's stage I (n = 4) and II (n = 3). Sites involved at presentation were cervical lymph nodes and tonsils (n = 5), ileum (n = 1) and parotid gland (n = 1). Three had complete surgical excision only and four had complete (n = 1) or incomplete excision (n= 3) followed by a short multi-agent chemotherapy regimen (UKCCSG 9001 protocol). With a median follow-up of 1.5 years (range 0.25-5 years) from diagnosis, six are alive in complete remission (CR) including three who had no chemotherapy. These results confirm previous reports that follicular lymphomas in children are rare (1.5%) and tend to be localized at presentation. Their rarity makes it difficult to produce guidelines about treatment, but in localized cases a period of non-intervention may be justified.

Antineoplastic Agents↗
PubMed1998

Multidrug resistance modulation in rhabdomyosarcoma and neuroblastoma cell lines.

Four rhabdomyosarcoma and three neuroblastoma cell lines were characterised for the presence of P-glycoprotein and MDR-1 expression using immunohistochemistry, northern analysis, RT-PCR and in situ mRNA hybridisation. None of the rhabdomyosarcoma lines were unequivocally positive in contrast to all three neuroblastoma lines. Chemosensitivity to cytotoxic agents was determined using the MTT assay and chemosensitisation by cyclosporin and verapamil was evaluated. In a single rhabdomyosarcoma line (HX 170) there was sensitisation to etoposide using verapamil but not to other drugs or using cyclosporin A. In contrast, in all three neuroblastoma lines both cyclosporin and verapamil sensitised to vincristine and doxorubicin. No evidence of sensitisation to etoposide was apparent. The sensitisation was most marked for vincristine, using either modulator and therefore the influence of modulator scheduling was evaluated with this drug in the neuroblastoma line SK N BE. Prolonged pre-exposure to modulator did not appear necessary and maximum sensitisation was apparent where either cyclosporin or verapamil was added 1-3 h prior to and post vincristine. Continuity of exposure was important and even a break of 30 min appeared to reduce sensitisation. These data confirm the potential for chemosensitisation in MDR-1 positive neuroblastoma cell lines and provide some basis for rational schedule design in clinical practice. Because of the probability that vincristine resistance is predominantly related to MDR-1 and less multifactorial than for other drugs such as doxorubicin or etoposide, this agent should be considered for inclusion in any clinical evaluation of MDR reversal strategies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Lung involvement in neuroblastoma: incidence and characteristics.

The presence of lung metastases in neuroblastoma often leads to doubt about the diagnosis due to rarity of disease at this site. To determine more precisely the incidence and nature of pulmonary disease in neuroblastoma the data base of the European Neuroblastoma Study Group (ENSG) was examined. Information was obtained about 35/746 stage IV patients (and 1 patient who was registered as having stage II disease) documented to have pulmonary disease at presentation. Of these 5 were registered with pleural effusions, 18 pleural infiltrations, and 13 intrapulmonary lesions. Review of these cases, however, suggested that only 9 patients (1.2%; 95% exact confidence interval 0.42-1.99%, binomial distribution) had disease consistent with secondary neuroblastoma in lung or pleura. There was no correlation with clinical features, age, sex, or other disease sites, and outcome was uniformly poor.

Adolescent↗
PubMed1997

Phase II study of 21 day schedule oral etoposide in children. New Agents Group of the United Kingdom Children's Cancer Study Group (UKCCSG).

We report a multicentre phase II study of orally administered prolonged schedule etoposide in children with refractory or relapsed malignancy. 83 children were entered into the study. The largest diagnostic groups were neuroblastoma (n = 20), rhabdomyosarcoma/soft tissue sarcoma (n = 16) and brain tumours (n = 16). Etoposide was administered twice daily at a dose of 50 mg/m2/day for 21 days using the intravenous preparation given orally. Disease reassessment was performed after the second course. Etoposide plasma concentrations were measured by HPLC, 2 and 6 h after administration of therapy on days 7 and 14 in 15 patients. 61 patients completed two courses and were evaluable for response. There was 1 complete response (CR), 5 partial responses (PR) 22 stable disease (SD) and 33 progressive disease (PD). Of the 6 with responses, 3 had a diagnosis of medulloblastoma/cerebral primitive neuroectodermal tumour. 24 of 26 patients with SD/PR/CR received further courses with excellent palliative effect. The main toxicity observed was myelosuppression, with 8% and 7% of evaluable courses complicated by grade III-IV neutropenia and thrombocytopenia, respectively. Severe infection (grade III-IV) was rare, complicating only 2/94 evaluable courses. Plasma etoposide median concentrations at 2 h after administration on day 7 of course 1 were 1.5 (range 0.6-2.4) micrograms/ml. Total course 1 area under the etoposide plasma concentration versus time curve (AUC) values were estimated using a limited sampling model. Grade > or = 2 leucopenia was only observed in patients with a day 72 h etoposide concentration of > 2 micrograms/ml or a course 1 AUC of > 35 mg/ml.min. It is concluded that given at a dose of 50 mg/m2/day in two doses for 21 day courses, oral etoposide is well tolerated in children. A correlation between drug concentrations and toxicity was observed. Overall, a low response rate was seen (approximately 10%), but disease stabilisation appears to occur, and useful palliative effect was frequently noted. The response in brain tumours was more encouraging (3/14 PR) and this group requires further evaluation.

Administration, Oral↗
PubMed1997

In vivo detection of ifosfamide by 31P-MRS in rat tumours: increased uptake and cytotoxicity induced by carbogen breathing in GH3 prolactinomas.

The direct detection and monitoring of anti-cancer drugs in vivo by magnetic resonance spectroscopy (MRS) may lead to improved anti-cancer strategies. 31P-MRS has been used to detect and quantify ifosfamide (IF) in vivo in GH3 prolactinomas and N-methyl-N-nitrosourea (MNU)-induced mammary tumours in rats. The average concentration of IF in the GH3 prolactinoma over the first 2 h following a dose of 250 mg kg-1 i.v. was calculated to be 0.42 micromol g-1 wet weight, with a half-life of elimination (t1/2) of 2-4 h. Carbogen (95% oxygen/5% carbon dioxide) breathing increased the amount of IF taken up by the GH3 prolactinoma by 50% (P<0.01) to 0.68 micromol g-1 wet weight, although t1/2 elimination rates were unchanged. IF was also detected in the liver in vivo, with a t1/2 of about 1 h. Carbogen breathing did not affect the maximum peak area (Cmax) or the t1/2 in the liver. Most importantly, the carbogen-induced increase in IF uptake by the tumour caused significant growth delay at all time points in the GH3 tumour growth between day 5 and day 12 (P< 0.01) compared with IF alone. These findings show that carbogen breathing has potential for increasing the efficacy of anti-cancer drugs. Isolated GH3 cells were sensitive to the parent drug (IF) in vitro (IC50 = 1.3 +/- 0.2 mM) suggesting that the GH3 cells may be either expressing P450 enzymes or are sensitive to the parent drug per se.

Animals↗
PubMed1997

Early identification of patients at risk of death due to infections, hemorrhage, or graft failure after allogeneic bone marrow transplantation on the basis of the leukocyte counts.

Allograft recipients are often unwell with significant organ dysfunction by the time delayed or failed engraftment is diagnosed. We attempted to identify factors associated with graft failure, or death due to infection, hemorrhage or graft failure in 712 patients undergoing allogeneic BMT. Low leukocyte counts between days 12 and 22 were strongly associated with subsequent graft failure or death. In multivariate analysis, a leukocyte count of < or = 0.2 x 10(9)/l on day 16 was the most powerful predictor of graft failure or death. Transplants from HLA-mismatched and unrelated donors were also associated with increased risk of both, and T cell depletion with increased risk of graft failure. On the basis of these findings, it may be possible to define graft failure in functional terms as early as 2 weeks after BMT rather than at 3 or 4 weeks. The use of growth factors can then be limited to patients most likely to benefit from them, and it may be possible to salvage patients at risk of complications of low counts early before their clinical condition deteriorates. We suggest that patients with leukocyte counts of 0.2 x 10(9)/l or less 14-16 days after BMT should be started on G-CSF or GM-CSF even if they are clinically well, and consideration should be given to a second infusion of cells.

Adolescent↗
PubMed1997

Outcome of acute leukemia relapsing after bone marrow transplantation: utility of second transplants and adoptive immunotherapy.

We studied 231 acute leukemia patients relapsing after allogeneic (n = 114) or autologous (n = 117) BMT to assess the outcome of further therapy. In general, all patients in good condition were eligible for second transplants except for post-allograft relapses from 1993-1994 onwards who received cytokine- or cell-mediated immunotherapy. The major reason for patients not progressing to second graft was death from progressive disease or toxicity of salvage chemotherapy. Seventeen of 231 patients (7%) were alive at the last follow-up. Six of 14 post-autograft relapses treated with second transplants were alive and well, compared with five of 103 not undergoing second grafts (P < 0.0001). One of 23 post-allograft recipients treated with second allografts was alive with an extramedullary relapse, compared with five of 13 receiving immunotherapy and none of 78 receiving standard-dose or palliative therapy (P < 0.0001). We conclude that only a small proportion of highly selected acute leukemia patients relapsing after a transplant reach the stage of a conventional second transplant. In our experience, second allografts after myeloablative therapy in patients relapsing after one allograft are associated with very poor results, and immunotherapy may be a better approach in such cases. Selected patients relapsing after an autograft may become long-term survivors following a second autograft or an allograft.

Acute Disease↗
PubMed1997

High-dose busulphan/melphalan with autologous stem cell rescue in Ewing's sarcoma.

Eighteen patients with poor risk Ewing's sarcoma (including 11 patients with metastatic disease at presentation) received consolidation therapy of busulphan and melphalan with autologous stem cell rescue. There were nine females. The median age at diagnosis was 14.2 years (range 2.75-30 years). There was one early death due to cytomegalovirus pneumonitis. One patient developed a single generalised convulsion during busulphan therapy. Severe renal toxicity was not encountered. One patient developed veno-occlusive disease of the liver (VOD) which eventually resolved. With a median follow up of 2 years, 13 patients survive including six with initial metastatic disease. We conclude that high-dose busulphan/melphalan is well-tolerated and should be evaluated for efficacy in a larger series of patients with high risk Ewing's sarcoma.

Adolescent↗
PubMed1997

Cytomegaloviremia after autografting for leukemia: clinical significance and lack of effect on engraftment.

One hundred and fourteen patients with leukemia (66 cytomegalovirus (CMV)-seropositive and 48 CMV-seronegative) were monitored for cytomegaloviremia by early antigen detection or conventional viral culture after autologous stem cell transplantation (ASCT). Twenty-two episodes of viremia were seen at 2-36 weeks (median 11) in 14 seropositive patients. Nineteen resolved without therapy in 11 patients. Three patients with clinical features suggestive of CMV disease were treated with ganciclovir: viremia resolved prior to ganciclovir in one, and with 3 weeks of ganciclovir in the other two. Transient thrombocytopenia (n = 4) and leukopenia (n = 1) were seen in association with five episodes of viremia. The counts recovered in all five patients; with ganciclovir (n = 2) or with spontaneous clearance of viremia (n = 3). One seronegative patient developed viremia which resolved spontaneously in 3 weeks. No symptoms suggestive of CMV disease were seen in any of the other patients. CMV serostatus or development of CMV infection did not affect hematologic recovery. In our experience, cytomegaloviremia is relatively uncommon after autografting for leukemia, and usually does not require treatment. We now do not routinely monitor leukemia patients for CMV infection after autografting, but look for viremia in CMV-seropositive patients with unexplained fever, drop in blood counts, lung infiltrates, or gastrointestinal symptoms.

Adolescent↗
PubMed1997

A randomized comparison of liposomal versus conventional amphotericin B for the treatment of pyrexia of unknown origin in neutropenic patients.

One hundred and thirty-four adults and 204 children were randomized in two prospective, parallel comparative multicentre trials to receive either conventional amphotericin B 1 mg/kg/d (c-AMB), liposomal amphotericin B 1 mg/kg/d(L-AMB1) or liposomal amphotericin B 3 mg/ kg/d (L-AMB3). Patients were entered if they had a pyrexia of unknown origin (PUO) defined as temperature of 38 degrees C or more, not responding to 96 h of systemic broad-spectrum antibiotic treatment, and neutropenia (< 0.5 x 10(9)/l). The safety and toxicity of liposomal amphotericin B was compared with that of conventional amphotericin B. Efficacy of treatment was assessed, with success defined as resolution of fever for 3 consecutive days (< 38 degrees C) without the development of any new fungal infection. Clinical and laboratory parameters were collected for safety analysis. In both the paediatric and adult populations, L-AMB treated patients had a 2-6-fold decrease in the incidence (P < or = 0.01) of test-drug-related side-effects, compared to c-AMB. Severe trial-drug-related side-effects were seen in 1% of L-AMB treated patients, in contrast to 12% of patients on c-AMB (P < 0.01). Nephrotoxicity, in the patient subset not receiving concomitant nephrotoxic agents, defined as a doubling from the patients baseline serum creatinine level, was not observed in the L-AMB1 arm whereas the incidence was 3% in patients on L-AMB3 and 23% in those on c-AMB (P < 0.01). Moreover, time to develop nephrotoxicity was longer in both L-AMB arms than c-AMB (P < 0.01). Severe hypokalaemia was observed less frequently in both L-AMB arms (P < 0.01). Analysis was by intention-to-treat and included all patients randomized. Success was defined by a minimum of 3 consecutive days with fever (< 38 degrees C) continuing to study end indicated by recovery of neutrophils to 0.5 x 10(9)/l. Addition of systemic antifungal therapy or development of systemic fungal infection were failures as was persistent fever to study end. Efficacy assessments indicated success in 49% of the total group treated with c-AMB, 58% of patients responded to L-AMB1 and 64% to L-AMB3. A statistically significant difference was found between c-AMB and L-AMB3 (P = 0.03) but a Kaplan-Meier analysis of time to differvescence of fever showed there was no significant difference between the arms. It was concluded that liposomal amphotericin at either 1 or 3 mg/kg/d was significantly safer than conventional amphotericin B in children and adults. The main aim of this open-label study was to compare safety between the three trial arms. However, we provide evidence for an equivalent or possibly superior efficacy of liposomal amphotericin with regard to resolution of fever of unknown origin. Subsequent trials should compare amphotericin preparations in defined fungal infections.

Adult↗
PubMed1997

Donor lymphocyte infusion for childhood acute lymphoblastic leukaemia relapsing after bone marrow transplantation.

Four children with acute lymphoblastic leukaemia (ALL) who relapsed after allogeneic bone marrow transplantation (BMT) were treated with donor lymphocyte infusion (DLI) without prior conditioning. Three patients had previously received a non-T-cell-depleted matched sibling BMT and the fourth had a T-cell-depleted matched unrelated BMT. Two patients developed grade III-IV acute graft-versus-host-disease (GVHD) of the skin, which required intervention. Both are alive in complete haematological remission 7 and 10 months from DLI with chronic GVHD of the skin requiring immunosuppressive therapy. A third patient went into haematological remission 6 weeks after DLI, but with no clinical evidence of GVHD. His bone marrow remained in remission 11 months post-DLI despite the disease (ALL) relapsing in extramedullary sites. The fourth patient showed no clinical or haematological response to three consecutive doses of DLI given at 4-weekly intervals and died from progressive disease 11 months after relapse. These preliminary observations indicate that in constrast to experience in adult ALL, DLI may be effective in inducing sustained remission in children with ALL relapsing after BMT, and a response may occur even in the absence of clinical evidence of GVHD.

Adolescent↗
PubMed1997

Granulocyte colony-stimulating factor in established febrile neutropenia: a randomized study of pediatric patients.

PURPOSE: Infection in neutropenic patients is potentially life-threatening and carries important implications for hospital resource use. Prophylactic administration of cytokines may reduce the severity of neutropenia, but involves the treatment of all patients for the possible benefit of a minority. This study evaluates whether treatment with cytokines in the setting of established febrile neutropenia will influence outcome and be potentially more cost-effective. PATIENTS AND METHODS: In a double-blind study, pediatric patients with fever and severe neutropenia were randomized to receive granulocyte colony-stimulating factor ([G-CSF] filgrastim; 5 microg/kg/d) or placebo, in addition to antibiotics. The study protocol required a resolution of fever and a neutrophil count > or = 0.2 x 10(9)/L for hospital discharge. Patients could be randomized for up to four independent febrile episodes. A total of 186 episodes of febrile neutropenia were investigated. RESULTS: Patients randomized to G-CSF had a shorter hospital stay (median, 5 v 7 days; P = .04) and fewer days of antibiotic use (median, 5 v 6 days; P = .02). G-CSF-treated patients also had more rapid neutrophil recovery and higher neutrophil levels at discharge. The 2-day reduction in hospital stay reduced the median bed cost by 29% per patient admission (P = .04). CONCLUSION: Under the clinical guidelines of our institution, the use of G-CSF in the treatment of established febrile neutropenia produced a small but significant reduction in the time that children required antibiotics and hospital admission, with possible cost savings.

Anti-Bacterial Agents↗