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Biomedical subjects

M Boyer

Publications and source records attributed to M Boyer.

At least 19 recordsLinked to original sources
PubMed2002

CTX-M-1, CTX-M-3, and CTX-M-14 beta-lactamases from Enterobacteriaceae isolated in France.

Six clinical CTX-M-producing isolates of the family Enterobacteriaceae were detected between 1999 and 2000 in different French hospitals. Two strains produced CTX-M-1 and CTX-M-3 and four strains produced CTX-M-14, a mutant Ala-231-->Val of CTX-M-9. A putative transposable element, ISEcp-1, was located 43 bp upstream of all the bla(CTX-M) genes. Two CTX-M-14-encoding plasmids exhibited similar restriction patterns. The CTX-M-1- and CTX-M-3-encoding plasmids were related to the CTX-M-1- and CTX-M-3-encoding plasmids previously reported in 1990 in France and in 1998 in Poland, respectively.

DNA Transposable Elements↗
PubMed2001

Highly sensitive analysis of the antifolate pemetrexed sodium, a new cancer agent, in human plasma and urine by high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatography method was developed and validated for the quantitation of pemetrexed (LY231514, ALIMTA) in human urine and plasma. Plasma samples were spiked with the internal standard lometrexol and extracted using Certify II columns. Pemetrexed was assayed in diluted urine by an external calibration method. A C8 column was used for the separation of analytes with a mobile phase composed of sodium formate buffer and acetonitrile. Between- and within-day precision and accuracy were acceptable down to the limit of quantitation of 5 ng/ml in plasma. This method was used successfully for an investigation of the disposition of pemetrexed in patients receiving 500 mg/m2 as a 10-min infusion.

Antineoplastic Agents↗
PubMed2001

Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study.

PURPOSE: To compare the efficacy and safety of orally administered capecitabine (Xeloda; Roche Laboratories, Inc, Nutley, NJ), a novel fluoropyrimidine carbamate designed to mimic continuous fluorouracil (5-FU) infusion but with preferential activation at the tumor site, with that of intravenous (IV) 5-FU plus leucovorin (5-FU/LV) as first-line treatment for metastatic colorectal cancer. PATIENTS AND METHODS: We prospectively randomized 602 patients to treatment with capecitabine 1,250 mg/m(2) administered twice daily days 1 to 14 every 3 weeks, or to the 4-weekly Mayo Clinic regimen (5-FU/LV) until disease progression or unacceptable toxicity. RESULTS: The primary objective, to demonstrate at least equivalent response rates in the two treatment groups, was met. The overall response rate was 18.9% for capecitabine and 15.0% for 5-FU/LV. In the capecitabine and 5-FU/LV groups, respectively, median time to disease progression was 5.2 and 4.7 months (log-rank P =.65); median time to treatment failure was 4.2 and 4.0 months (log-rank P =.89); and median overall survival was 13.2 and 12.1 months (log-rank P =.33). The toxicity profiles of both treatments were typical of fluoropyrimidines. However, capecitabine led to significantly lower incidences (P <.00001) of stomatitis and alopecia, but a higher incidence of cutaneous hand-foot syndrome (P <.00001). Capecitabine also resulted in lower incidences (P <.00001) of grade 3/4 stomatitis and neutropenia, leading to a lower incidence of grade 3/4 neutropenic fever and sepsis. Only grade 3 hand-foot syndrome (P <.00001) and uncomplicated grade 3/4 hyperbilirubinemia (P <.0001) were reported more frequently with capecitabine. CONCLUSION: Oral capecitabine achieved an at least equivalent efficacy compared with IV 5-FU/LV. Capecitabine demonstrated clinically meaningful safety advantages and the convenience of an oral agent.

Adenocarcinoma↗
PubMed2001

Characterization of the folding and unfolding reactions of a small beta-barrel protein of novel topology, the MTCP1 oncogene product P13.

The equilibrium and kinetic folding properties of a small oncogene product, P13(MTCP1), of novel topology have been investigated using perturbation by guanidine hydrochloride and observation by fluorescence, circular dichroism and two-dimensional heteronuclear NMR spectroscopy. The structure of P13(MTCP1) is comprised of a canonical filled beta-barrel, although the topology of the structure is absolutely unique, rendering the folding properties of this protein of great interest. Equilibrium measurements of the intrinsic fluorescence emission spectrum, the fluorescence decay, the circular dichroism spectrum and the (15)N-(1)H heteronuclear single quantum coherence (HSQC) correlation spectrum as a function of increasing concentrations of denaturant showed no evidence for the population of any equilibrium intermediates, although negative amplitudes on the blue edge of the tryptophan emission and loss of intensity of the native HSQC correlation peaks were indicative of increased conformational dynamics at low denaturant concentrations. The free energy and cooperativity of unfolding as observed by fluorescence and circular dichroism were in relatively good agreement, also consistent with a two-state transition. Kinetics measurements of the fluorescence emission as a function of denaturant concentration revealed that P13(MTCP1) is the slowest folding beta-structure protein reported to date. Comparison of the activation cooperativity values (m(f) and m(u)) indicates that the structure of the transition state is quite close to the folded state in terms of exposed surface area. The calculated contact order of P13(MTCP1) is relatively low and does not appear to explain its slow rate of folding. We suggest that the complex topology of this protein, which would require the ordering of the beta-barrel through a long loop joining the two L-shaped components of the barrel, could provide an explanation for this slow folding.

Circular Dichroism↗
PubMed2001

Carboplatin and vinorelbine in untreated locally advanced and metastatic non-small cell lung cancer.

The aim of this study was to assess the activity and toxicity of carboplatin/vinorelbine combination chemotherapy in unresectable locally advanced and metastatic non-small cell lung cancer. Between April 1997 and June 1999 30 patients (22 M, eight F, median age 62) received treatment with carboplatin AUC 6 on day 1, and vinorelbine 25mg/m(2) on days 1, 8 and 15. Treatment was given every 28 days for six cycles unless progressive disease occurred. Twenty-three patients (77%) had stage IV disease, and seven (23%) stage IIIB. Ninety-three percent were WHO performance status 0-1. Twenty-three patients were fully assessable. Nine patients achieved partial responses (9/23, 39%) for an overall objective response rate of 9/30 (30%; 95% CI 15-49%). The median duration of response was 2.75 months (range 1-13 months). The median progression-free survival was 2 months and the median survival 5.25 months. The actuarial 1-year survival was 20%. The median number of cycles completed was two (range 1-6). Day 15 vinorelbine was administered in only 18% of cycles. The main toxicity was myelosuppression. WHO grade III/IV neutropenia was experienced in 50% of patients, however, there were only three episodes of febrile neutropenia. Eight patients required blood transfusion and one developed grade III thrombocytopenia. Treatment was ceased in one patient because of grade IV autonomic neuropathy. No patient had significant nausea and vomiting. There were no treatment-related deaths. These results indicate that carboplatin/vinorelbine is well tolerated and has similar activity to cisplatin/vinorelbine in patients with unresectable non-small cell lung cancer, however, the median survival was considerably shorter.

Actuarial Analysis↗
PubMed2001

[Evaluation of the E-test and the ATB-PNEUMo battery for determining the beta-lactam MIC for Streptococcus pneumoniae in daily practice].

In 1999, during the survey of resistance of Streptococcus pneumoniae to antibiotics by 31 clinical laboratories of Rhône-Alpes area, MIC to penicillin (P), amoxicillin (AMX) and cefotaxime (CTX) of 877 PRP strains or with a diameter of inhibition to oxacillin inferior to 26 mm, were determined by each institution by E-test (n = 220 strains) or ATB-PNEUMO (n = 657 strains). MICs of these three antibiotics were determined by dilution in agar medium by the coordinating center. The essential agreement was respectively for ATB-PNEUMO and E-test 89% versus 84% for P (p > 0.05), of 86% vs 79% for AMX (p < 0.01), and of 91% vs 86% for CTX (p = 0.03). When the strains were classified in clinical category, the differences were significant (p < 0.001) for AMX (85% vs 71%) and for CTX (82% vs 75%) but not for P (73% vs 78%). ATB-PNEUMO method was more sensitive than E-test for the detection of strains susceptible to P (90 vs 73%), to AMX (83 vs 78%) and to CTX (80 vs 72%) and for the strains intermediate to AMX (90 vs 78%). On the contrary, E-test is more specific than ATB-PNEUMO for the detection of P-resistant strains (94 vs 86%). Finally, the specificity of both methods is the same for detection of P-S, AMX-R and CTX-I strains.

Amoxicillin↗
PubMed2001

Capecitabine (Xeloda) improves medical resource use compared with 5-fluorouracil plus leucovorin in a phase III trial conducted in patients with advanced colorectal carcinoma.

Standard therapy for advanced or metastatic colorectal cancer consists of 5-fluorouracil plus leucovorin (5-FU/LV) administered intravenously (i.v.). Capecitabine (Xeloda), an oral fluoropyrimidine carbamate which is preferentially activated by thymidine phosphorylase in tumour cells, mimics continuous 5-FU and is a recently developed alternative to i.v. 5-FU/LV. The choice of oral rather than intravenous treatment may affect medical resource use because the two regimens do not require the same intensity of medical intervention for drug administration, and have different toxicity profiles. Here we examine medical resource use in the first-line treatment of colorectal cancer patients with capecitabine compared with those receiving the Mayo Clinic regimen of 5-FU/LV. In a prospective, randomised phase III clinical trial, 602 patients with advanced or metastatic colorectal cancer recruited from 59 centres worldwide were randomised to treatment with either capecitabine or the Mayo regimen of 5-FU/LV. In addition to clinical efficacy and safety endpoints, data were collected on hospital visits required for drug administration, hospital admissions, and drugs and unscheduled consultations with physicians required for the treatment of adverse events. Capecitabine treatment in comparison to 5-FU/LV in advanced colorectal carcinoma resulted in superior response rates (26.6% versus 17.9%, P=0.013) and improved safety including less stomatitis and myelosuppression. Capecitabine patients required substantially fewer hospital visits for drug administration than 5-FU/LV patients. Medical resource use analysis showed that patients treated with capecitabine spent fewer days in hospital for the management of treatment related adverse events than did patients treated with 5-FU/LV. In addition, capecitabine reduced the requirement for expensive drugs, in particular antimicrobials fluconazole and 5-HT3-antagonists to manage adverse events. As anticipated with an oral home-based therapy patients receiving capecitabine needed more frequent unscheduled home, day care, office and telephone consultations with physicians. In the light of clinical results from the phase III trial demonstrating increased efficacy in terms of response rate, equivalent time to progression (TTP) and survival (OS), and a superior safety profile, the results from this medical resource assessment indicate that capecitabine treatment of colorectal cancer patients results in a substantial resource use saving relative to the Mayo Clinic regimen of 5-FU/LV. This benefit is derived principally from the avoidance of hospital visits for i.v. drug administration, less expensive drug therapy for the treatment of toxic side-effects, and fewer treatment-related hospitalisations required during the course of therapy for adverse drug reactions in comparison to patients treated with 5-FU/LV.

Adult↗
PubMed2000

Quantitative characterization of the interaction between purified human estrogen receptor alpha and DNA using fluorescence anisotropy.

In an effort to better define the molecular mechanisms of the functional specificity of human estrogen receptor alpha, we have carried out equilibrium binding assays to study the interaction of the receptor with a palindromic estrogen response element derived from the vitellogenin ERE. These assays are based on the observation of the fluorescence anisotropy of a fluorescein moiety covalently bound to the target oligonucleotide. The low anisotropy value due to the fast tumbling of the free oligonucleotide in solution increases substantially upon binding the receptor to the labeled ERE. The quality of our data are sufficient to ascertain that the binding is clearly cooperative in nature, ruling out a simple monomer interaction and implicating a dimerization energetically coupled to DNA binding in the nanomolar range. The salt concentration dependence of the affinity reveals formation of high stoichiometry, low specificity complexes at low salt concentration. Increasing the KCl concentration above 200 mM leads to specific binding of ER dimer. We interpret the lack of temperature dependence of the apparent affinity as indicative of an entropy driven interaction. Finally, binding assays using fluorescent target EREs bearing mutations of each of the base pairs in the palindromic ERE half-site indicate that the energy of interaction between ER and its target is relatively evenly distributed throughout the site.

Base Sequence↗
PubMed2000

Isolation of endothelial cells and their progenitor cells from human peripheral blood.

PURPOSE: We have developed techniques to isolate endothelial cell (EC) progenitors from human peripheral and umbilical cord blood. METHODS: Human adult peripheral and umbilical cord blood monocytes were isolated by centrifugation, and progenitor cells were separated with the use of magnetic polystyrene beads that were coated with a monoclonal antibody specific for the CD34 cell-membrane antigen. Cells were propagated in selective media, and developing cultures were immunostained for CD31, CD34, factor VIII, and vascular endothelial growth factor cell receptors. ECs that developed were transfected with a gene for prourokinase and used to line ePTFE grafts, which were evaluated in vitro in a pulsatile flow system. RESULTS: Umbilical cord monocyte cultures demonstrated colonies that resembled ECs at approximately 2 weeks, with growth being best supported by EC growth media plus 20% calf serum with iron. Immunostaining of colonies was positive for CD31 and factor VIII. After 18 days in culture, CD34(+) cells from adult peripheral blood were noted, which had the typical cobblestone appearance of ECs and immunostained positively for CD31 and factor VIII-related antigens. Cultures of umbilical cord-derived cells and adult peripheral blood-derived cells developed complex line formations within 1 week in culture that stained positively for vascular endothelial growth factor receptor-2. Urokinase-transfected ECs were shown to overexpress urokinase. Prosthetic grafts lined with transfected cells showed 87.33% +/- 4.97% cell adherence after 2 hours in a pulsatile flow system at clinically relevant shear stress. CONCLUSION: We conclude that endothelial progenitor cells can be isolated from human adult peripheral and umbilical cord blood and developed into EC cultures as a source of cells for vascular graft seeding and gene therapy.

Adult↗
PubMed2000

Hydroxychloroquine for the treatment of chronic graft-versus-host disease.

Chronic graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation. Both the disease and the medications used to treat it are associated with significant morbidity and mortality. The manifestations of chronic GVHD often resemble those of autoimmune disorders. Hydroxychloroquine (HCQ) is a 4-aminoquinoline antimalarial drug used for the treatment of autoimmune diseases. HCQ interferes with antigen processing and presentation, cytokine production, and cytotoxicity and is synergistic with cyclosporine and tacrolimus in vitro. Forty patients with steroid-resistant or steroid-dependent chronic GVHD were enrolled in a phase 2 trial of HCQ 800 mg (12 mg/kg) per day. Three complete responses and 14 partial responses were seen in 32 evaluable patients (53% response rate). All responders tolerated a >50% reduction in their steroid dose while receiving HCQ. Clinical response occurred at a median of 8 weeks (range, 4 to 24 weeks). No hematologic, hepatic, renal, or retinal toxicity was associated with HCQ. In light of its mechanisms of action, clinical activity for GVHD, and low toxicity profile, HCQ may be useful in a multiagent approach for the treatment of extensive chronic GVHD.

Adolescent↗
PubMed2000

A phase I trial of docetaxel and gemcitabine in patients with advanced cancer.

BACKGROUND: Docetaxel and gemcitabine are active in a broad range of malignancies. The objective of this phase I trial was to determine the maximally tolerated doses of the combination of docetaxel and gemcitabine. PATIENTS AND METHODS: Patients with advanced cancer, WHO performance status 0-2, who had received up to one prior chemotherapy regimen were treated with gemcitabine on days 1 and 8 and docetaxel on day 8 repeated every 21 days. Prophylactic ciprofloxacin was commenced on day 11 of each cycle and continued until the neutrophil count reached 1.0 x 10(9)/l. G-CSF was not administered. Dose levels studied were docetaxel/gemcitabine: 60/800, 60/1000, 75/1000, 75/1200, 85/1200 and 100/1200 mg/m2. RESULTS: Thirty-nine patients were entered and all were assessable for toxicity. The highest administered dose level was 100 mg/m2 docetaxel and 1200 mg/m2 gemcitabine with dose limiting toxicities of febrile neutropenia, grade 4 neutropenia > or = 7 days, grade 4 thrombocytopenia, grade 3 stomatitis and/or grade 3 fatigue in three out of six patients. Treatment was well tolerated (40 cycles) in the 10 patients treated at the recommended dose level (85/1200) with only a single episode of febrile neutropenia and grade 3 or 4 non-hematologic toxicity was infrequent. There was no significant pulmonary toxicity. Responses were seen in a range of malignancies including non-small-cell lung cancer. CONCLUSIONS: The recommended dose level of 85 mg/m2 docetaxel and 1200 mg/m2 gemcitabine has a favourable toxicity profile and is suitable for further investigation in phase II trials. This non-platinum containing regimen warrants further investigation as a potential alternative to platinum containing regimens in non-small-cell lung cancer and other malignancies.

Adult↗
PubMed2000

New strategies in allogeneic stem cell transplantation: immunotherapy using irradiated allogeneic T cells.

Recipients of T cell-depleted allogeneic bone marrow transplants have increased risks of relapse and graft rejection. The addition of donor T cells to the TCD allograft will decrease the risk of graft rejection but will increase the risk of graft-versus-host disease (GVHD). Relapse of leukemia or lymphoma following allogeneic bone marrow transplantation can be successfully treated with post-transplant infusions of donor lymphocytes. A relatively small number of donor T cells can have a profound anti-tumor effect and facilitate engraftment, but has an unpredictable potential for severe GVHD. An alternative to using viable immunocompetent donor immune cells to facilitate engraftment and to treat relapsed patients are donor lymphocytes that have been treated to limit their ability to proliferate and cause GVHD. T cells treated with irradiation retain cytotoxic activity against tumor cells and host immune cells. We have tested the hypothesis that allogeneic donor T cells treated with low-dose irradiation will facilitate engraftment and mediate an anti-leukemia effect in a mouse model of bone marrow transplantation. Multiple infusions of irradiated allogeneic donor lymphocytes in the peri-transplant period had graft-enhancing activity without resulting in GVHD. Murine recipients of irradiated allogeneic splenocytes and allogeneic bone marrow had stable donor-derived hematopoiesis without a significant contribution of irradiated donor cells to the T cell compartment. Removing T cells from the allogeneic splenocytes prior to irradiation largely eliminated their graft facilitating activity. Based upon the promising results of the pre-clinical murine studies, we initiated a phase I clinical trial of multiple infusions of irradiated allogeneic lymphocytes in patients who had relapsed after allogeneic BMT. Of 12 patients treated to date on this study, three have shown objective responses of their leukemia or lymphoma to multiple infusions of irradiated donor lymphocytes. We have initiated a new phase I clinical study to test the efficacy of multiple infusions of irradiated allogeneic cytotoxic T cells to facilitate engraftment in allogeneic transplantation. Successive cohorts of patients will be transplanted with allogeneic stem cells alone, or a combination of allogeneic stem cells and increasing numbers of irradiated allogeneic T cells. Irradiated allogeneic lymphocytes that retain short-term allo-specific cytotoxicity and lack the potential for clonal expansion in vivo can be considered as a novel form of immunotherapy with defined pharmacokinetics.

Animals↗
PubMed2000

Retrovirus-mediated transduction of primary ZAP-70-deficient human T cells results in the selective growth advantage of gene-corrected cells: implications for gene therapy.

Humans lacking the ZAP-70 protein tyrosine kinase present with an absence of CD8+ T cells and defective CD4+ T cells in the periphery. This severe combined immunodeficiency is fatal unless treated by allogeneic bone marrow transplantation. However, in the absence of suitable marrow donors, the development of alternative forms of therapy is desirable. Because lymphocytes are long-lived, it is possible that introduction of the wild-type ZAP-70 gene into CD4+ ZAP-70-deficient T cells will restore their immune function in vivo. Initial investigations evaluating the feasibility of gene therapy for ZAP-70 deficiency were performed using HTL V-I-transformed lymphocytes. Although transformation was useful in circumventing problems associated with the maintenance of ZAP-70-deficient T cells and low gene transfer levels, the presence of HTL V-I precluded any biological studies. Here, we investigated a retrovirus-mediated approach for the correction of primary T cells derived from two ZAP-70-deficient patients. Upon introduction of the wild-type ZAP-70 gene, TCR-induced MAPK activation, IL-2 secretion and proliferation were restored to approximately normal levels. Importantly, this gain-of-function was associated with a selective growth advantage of gene-corrected cells, thereby indicating the feasibility of a gene therapy-based strategy.

Cell Division↗
PubMed2000

A phase II trial of paclitaxel and epirubicin in advanced breast cancer.

Initial trials of paclitaxel and doxorubicin in advanced breast cancer yielded high response rates but significant cardiac toxicity was observed. In this phase II trial we investigated the efficacy and safety of paclitaxel combined with epirubicin. Patients with advanced breast cancer, performance status 0-2, measurable disease, and a normal left ventricular ejection fraction, who may have received adjuvant chemotherapy were treated with epirubicin 75 mg m(-2) followed by a 3-h infusion of paclitaxel 175 mg m(-2) repeated every 3 weeks. Forty-three eligible patients were treated at six centres. 67% patients received the maximum of six cycles. The response rate was 54% (95% CI 38-69%), 12% CR and 42% PR. Estimated median progression-free survival was 6.9 months (95% CI 5.4-10.0) and estimated median overall survival was 17.9 months (95% CI 14.2-25.7). Four patients had a decrease in the left ventricular ejection fraction (LVEF) of > or =20% of baseline value, and in two patients the LVEF decreased to below the lower limit of normal, but no patient developed clinical evidence of cardiac failure. Grade 4 neutropenia occurred in 56% cycles, but only 4% of cycles were complicated by febrile neutropenia. Grade 3 or 4 non-haematologic toxicity was uncommon. In conclusion, paclitaxel 175 mg m(-2) and epirubicin 75 mg m(-2) is a well tolerated, promising regimen for the treatment of advanced breast cancer.

Adult↗
PubMed2000

Nonviral in vivo gene therapy for tissue engineering of articular cartilage and tendon repair.

Heretofore, nonviral methods have been used primarily for in vitro transfection of cultured cell lines. These methods were substantially less efficient when compared with the use of viruses, particularly when used in vivo. Herein a three-step, highly efficient method of nonviral gene delivery is presented. Using this method, genes have been delivered successfully into tissues of orthopaedic importance with high-efficiency by nonviral means. Transforming growth factor-beta 1, parathyroid hormone related protein, and a marker gene were transfected into primary perichondrium and cartilage cells with efficiencies in excess of 70%. They overexpressed their cognate gene products showing efficacy of expression in a rabbit model of osteochondral defect repair. Using the same method, a marker gene was delivered into a canine model for intrasynovial flexor tendon injury and repair. This was achieved by direct gene delivery during surgery. An estimated 5 additional minutes were required during surgery to complete the transfection steps. High efficiency gene delivery was achieved in the flexor tendons, tendon sheaths, tendon pulleys, surrounding tissues, and skin. The efficiency of transfection approached 100% in the exposed superficial tissue layers and transfected cells were found several layers below the exposed tissue surfaces. The data show the potential of direct nonviral gene therapy in orthopaedics for ex vivo and in vivo applications.

Animals↗
PubMed2000

Identification of group B streptococcal Sip protein, which elicits cross-protective immunity.

A protein of group B streptococci (GBS), named Sip for surface immunogenic protein, which is distinct from previously described surface proteins, was identified after immunological screening of a genomic library. Immunoblots using a Sip-specific monoclonal antibody indicated that a protein band with an approximate molecular mass of 53 kDa which did not vary in size was present in every GBS strain tested. Representatives of all nine GBS serotypes were included in the panel of strains. Cloning and sequencing of the sip gene revealed an open reading frame of 1,305 nucleotides coding for a polypeptide of 434 amino acid residues, with a calculated pI of 6. 84 and molecular mass of 45.5 kDa. Comparison of the nucleotide sequences from six different strains confirmed with 98% identity that the sip gene is highly conserved among GBS isolates. N-terminal amino acid sequencing also indicated the presence of a 25-amino-acid signal peptide which is cleaved in the mature protein. More importantly, immunization with the recombinant Sip protein efficiently protected CD-1 mice against deadly challenges with six GBS strains of serotypes Ia/c, Ib, II/R, III, V, and VI. The data presented in this study suggest that this highly conserved protein induces cross-protective immunity against GBS infections and emphasize its potential as a universal vaccine candidate.

Amino Acid Sequence↗
PubMed2000

The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients.

PURPOSE: Febrile neutropenia remains a potentially life-threatening complication of anticancer chemotherapy, but some patients are at low risk for serious medical complications. The purpose of this study was to develop an internationally validated scoring system to identify these patients. MATERIALS AND METHODS: Febrile neutropenic cancer patients were observed in a prospective multinational study. Independent factors assessable at fever onset, predicting low risk of complications, on a randomly selected derivation set, were assigned integer weights to develop a risk-index score, which was subsequently tested on a validation set. RESULTS: On the derivation set (756 patients), predictive factors were a burden of illness indicating absence of symptoms or mild symptoms (weight, 5; odds ratio [OR], 8.21; 95% confidence interval [CI], 4.15 to 16.38) or moderate symptoms (weight, 3; OR, 3.70; 95% CI, 2.18 to 6.29); absence of hypotension (weight, 5; OR, 7.62; 95% CI, 2.91 to 19.89); absence of chronic obstructive pulmonary disease (weight, 4; OR, 5. 35; 95% CI, 1.86 to 15.46); presence of solid tumor or absence of previous fungal infection in patients with hematologic malignancies (weight, 4; OR, 5.07; 95% CI, 1.97 to 12.95); outpatient status (weight, 3; OR, 3.51; 95% CI, 2.02 to 6.04); absence of dehydration (weight, 3; OR, 3.81; 95% CI, 1.89 to 7.73); and age less than 60 years (weight, 2; OR, 2.45; 95% CI, 1.51 to 4.01). On the validation set, a Multinational Association for Supportive Care in Cancer risk-index score >/= 21 identified low-risk patients with a positive predictive value of 91%, specificity of 68%, and sensitivity of 71%. CONCLUSION: The risk index accurately identifies patients at low risk for complications and may be used to select patients for testing therapeutic strategies that may be more convenient or cost-effective.

Anti-Bacterial Agents↗