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1.
BMC Cancer ; 21(1): 454, 2021 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-33892670

RESUMEN

BACKGROUND: The objective of this study was to compare the efficacy and side effects of a single dose (Pegfilgrastim or PDL) or repeated six daily injections (Filgrastim or PDG) during chemotherapy courses in breast cancer patients in a non-inferiority clinical trial. METHODS: In this randomized clinical trial, 80 patients were recruited and allocated randomly to two equal arms. In one group, a single subcutaneous dose of PDL was injected the day after receiving the chemotherapy regimen in each cycle. The second arm received a subcutaneous injection of PDG for six consecutive days in each cycle of treatment. The side effects of GCF treatment and its effect on blood parameters were compared in each cycle and during eight cycles of chemotherapy. RESULTS: Hematologic parameters showed no significant differences in any of the treatment courses between the two study groups. The comparison of WBC (p = 0.527), Hgb (p = 0.075), Platelet (p = 0.819), Neutrophil (p = 0.575), Lymphocyte (p = 705) and ANC (p = 0.675) changes during the eight courses of treatment also revealed no statistically significant difference between the two study groups. Side effects including headache, injection site reaction and muscle pain had a lower frequency in patients receiving PDL drugs. CONCLUSION: It seems that PDL is non-inferior in efficacy and also less toxic than PDG. Since PDL can be administered in a single dose and is also less costly, it can be regarded as a cost-effective drug for the treatment of chemotherapy-induced neutropenia. TRIAL REGISTRATION: IRCT20190504043465N1 , May 2019.


Asunto(s)
Neoplasias de la Mama/sangre , Neutropenia Febril Inducida por Quimioterapia/tratamiento farmacológico , Filgrastim/administración & dosificación , Fármacos Hematológicos/administración & dosificación , Polietilenglicoles/administración & dosificación , Adulto , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Recuento de Células Sanguíneas , Neoplasias de la Mama/tratamiento farmacológico , Neutropenia Febril Inducida por Quimioterapia/sangre , Femenino , Filgrastim/efectos adversos , Filgrastim/economía , Fármacos Hematológicos/efectos adversos , Fármacos Hematológicos/economía , Humanos , Inyecciones Subcutáneas , Persona de Mediana Edad , Polietilenglicoles/efectos adversos , Polietilenglicoles/economía
2.
Cancer Rep (Hoboken) ; 3(5): e1266, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32761893

RESUMEN

BACKGROUND: Pegfilgrastim, a pegylated granulocyte colony-stimulating-factor (GCSF), reduces chemotherapy morbidity and mortality in early stage breast cancer. The optimal approach to individual patient selection for GCSF is unknown, in particular whether secondary GCSF should be given after asymptomatic neutropenia, or only after febrile neutropenia (FN). AIMS: To determine if preplanned nadir blood counts and subsequent nadir-neutropenia directed GCSF was effective to reduce rates of FN associated with (neo)adjuvant breast cancer chemotherapy. We also aimed to describe (neo)adjuvant chemotherapy and GCSF prescribing practices at our institution. METHODS: This was a retrospective electronic medical record review. The rate of FN with secondary GCSF after cycle 1 nadir-neutropenia <1.0 × 109 cells/L was compared with the rate of FN in patients who did not have cycle 1 nadir blood counts or secondary GCSF, and analyzed according to patient and treatment data. RESULTS: Between 11/4/2011 and 22/4/2018, 584 patients received (neo)adjuvant chemotherapy. Over all rates of FN were 17%, compared with 9% in patients who received primary GCSF. Rates of FN were highest in docetaxel/carboplatin/trastuzumab (TCH, 27%) and docetaxel/cyclophosphamide (TC, 27%). There were 268 patients (46%) who received primary GCSF and 238 patients (41%) who received secondary GCSF. Rates of FN did not differ between patients who received nadir-neutropenia directed secondary GCSF (6/125, 5%, 95% CI 1.1-8.6), and those who did not have nadir blood counts or secondary GCSF (0/49, 0%, 95% CI not calculable) (P = .1186). GCSF use was associated with lower rates of non-FN hospital admissions. Patients ≥65 years were more likely to have FN and non-FN admissions. Two of three treatment related deaths occurred due to FN. CONCLUSIONS: In this population, nadir-neutropenia directed secondary GCSF was not associated with reduced rates of FN. Observed rates of FN >20% in TC and TCH in routine clinical practice should guide primary GCSF use in accordance with international guidelines.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama Masculina/tratamiento farmacológico , Neoplasias de la Mama/tratamiento farmacológico , Neutropenia Febril Inducida por Quimioterapia/epidemiología , Filgrastim/administración & dosificación , Polietilenglicoles/administración & dosificación , Neoplasias de la Mama/sangre , Neoplasias de la Mama Masculina/sangre , Quimioterapia Adyuvante/efectos adversos , Neutropenia Febril Inducida por Quimioterapia/sangre , Neutropenia Febril Inducida por Quimioterapia/diagnóstico , Neutropenia Febril Inducida por Quimioterapia/prevención & control , Esquema de Medicación , Femenino , Humanos , Recuento de Leucocitos , Masculino , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/métodos , Neutrófilos , Valores de Referencia , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
4.
Future Oncol ; 16(14): 891-897, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32329365
5.
Support Care Cancer ; 28(3): 1289-1294, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31240465

RESUMEN

PURPOSE: To explore whether monocytes, lymphocytes, and platelets have a predictive value for short-term neutrophil changes in patients with severe neutropenia (SN) induced by chemotherapy. METHODS: Complete blood counts (CBC) were collected from a total of 62 patients with chemotherapy-induced SN from December 2013 to March 2018. CBCs at intervals of 1 day, 2 days, 3 days, 4 days, and 5 days were recorded, and logistic regression analyses were performed to determine whether the monocyte percentage (MP), absolute monocyte count (AMC), lymphocyte percentage (LP), absolute lymphocyte count (ALC), or platelet count (PC) were correlated with short-term neutrophil changes. The areas under the receiver operating characteristic (ROC) curves (AUCs) were calculated for parameters with a P value < 0.05. RESULTS: The MP was significantly correlated with changes in neutrophils for intervals of 1 to 5 days, while the LP was significantly correlated with changes in neutrophils for intervals of 2 to 5 days. A cutoff value of 6.5% for the MP yielded a sensitivity of 80%, a specificity of 88.6%, and an AUC of 0.908 for predicting an increase in neutrophils on the third day. A cutoff value of 14.75% for the LP yielded a sensitivity of 93.3%, a specificity of 70.3%, and an AUC of 0.812 for predicting an increase in neutrophils on the sixth day. CONCLUSIONS: In chemotherapy-induced neutropenia patients, the MP is the best predictor of short-term neutrophil changes. Close monitoring and proper interpretation of the MP and LP are informative in managing chemotherapy-induced neutropenia.


Asunto(s)
Antineoplásicos/uso terapéutico , Neutropenia Febril Inducida por Quimioterapia/diagnóstico , Linfocitos/patología , Monocitos/patología , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Neutrófilos/patología , Adulto , Anciano , Antineoplásicos/efectos adversos , Neutropenia Febril Inducida por Quimioterapia/sangre , Neutropenia Febril Inducida por Quimioterapia/patología , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
6.
Transpl Infect Dis ; 21(6): e13186, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31574202

RESUMEN

Bloodstream infection (BSI) remains a serious complication in patients with hematologic malignancies and neutropenia. The risk factors for mortality after BSI and the contributions of BSI pathogens to mortality remain incompletely understood. We evaluated first BSI among adult neutropenic patients undergoing high-dose chemotherapy for hematologic malignancies in the setting of (a) an early disease stage of autologous (auto-HSCT) or allogeneic (allo-HSCT) hematopoietic stem cell transplantation or (b) for acute leukemia. Risk factors for intensive care admission and all-cause mortality were analyzed by multivariable logistic regression 7 and 30 days after onset of the first BSI in the first neutropenic episode. Between 2002 and 2015, 9080 patients met the study inclusion criteria, and 1424 (16%) developed BSIs, most of them during the first week of neutropenia. Mortality during neutropenia within 7 days and 30 days after BSI onset was 2.5% and 5.1%, respectively, and differed considerably between BSI pathogens. Both 7-day and 30-day mortalities were highest for Pseudomonas aeruginosa BSI (16.7% and 26.7%, respectively) and lowest for BSI due to coagulase-negative Staphylococcus spp. (CoNS) and Streptococcus spp. BSI pathogens were independently associated with 7-day mortality included P aeruginosa, Klebsiella spp., Enterobacter spp., Serratia spp., and enterococci. Only gram-negative BSI and candidemia were associated with admission to intensive care within 7 days after BSI onset. BSI caused by P aeruginosa continues to carry a particularly poor prognosis in neutropenic patients. The unexpected association between enterococcal BSI and increased mortality needs further study.


Asunto(s)
Bacteriemia/mortalidad , Bacterias/patogenicidad , Neutropenia Febril Inducida por Quimioterapia/inmunología , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bacteriemia/inmunología , Bacteriemia/microbiología , Bacterias/inmunología , Bacterias/aislamiento & purificación , Neutropenia Febril Inducida por Quimioterapia/sangre , Neutropenia Febril Inducida por Quimioterapia/mortalidad , Estudios de Cohortes , Femenino , Neoplasias Hematológicas/inmunología , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Trasplante Autólogo/efectos adversos , Trasplante Homólogo/efectos adversos
7.
Anticancer Res ; 39(6): 3059-3065, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31177149

RESUMEN

BACKGROUND: Induction chemotherapy (IC) for head and neck cancer (HNC) often causes severe side-effects. However, it has still been challenging to predict the adverse events. The present study aimed to evaluate the role of hematological inflammatory markers in predicting severe side-effects caused by IC. MATERIALS AND METHODS: A total of 54 HNC patients who underwent IC were enrolled. The association between severe side-effects and pre-treatment hematological inflammatory markers [the C-reactive protein (CRP) to albumin ratio (CAR), the modified Glasgow Prognostic Score (mGPS), the neutrophil-to-lymphocyte ratio (NLR), and the platelet-to-lymphocyte ratio (PLR)] were evaluated. RESULTS: In the univariate analysis, the incidence of whole severe side-effects (grade 4), febrile neutropenia (above grade 3), and hyponatremia (above grade 3) were significantly higher in the high CAR and high GPS groups. Multivariate analysis revealed that high CAR and mGPS were independent predictors of these side-effects. CONCLUSION: CAR and mGPS were significant predictors of severe side-effects. These data can potentially offer patients an improved quality of life during cancer therapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neutropenia Febril Inducida por Quimioterapia/epidemiología , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Quimioterapia de Inducción/efectos adversos , Mediadores de Inflamación/sangre , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Neutropenia Febril Inducida por Quimioterapia/sangre , Neutropenia Febril Inducida por Quimioterapia/diagnóstico , Cisplatino/efectos adversos , Docetaxel/efectos adversos , Femenino , Fluorouracilo/efectos adversos , Neoplasias de Cabeza y Cuello/sangre , Neoplasias de Cabeza y Cuello/diagnóstico , Humanos , Hiponatremia/sangre , Hiponatremia/diagnóstico , Hiponatremia/epidemiología , Incidencia , Japón/epidemiología , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Estado Nutricional , Recuento de Plaquetas , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Albúmina Sérica Humana/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/sangre , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Factores de Tiempo , Resultado del Tratamiento
8.
Cancer Invest ; 37(3): 156-162, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30907154

RESUMEN

Mannose-binding lectin (MBL) - deficient patients who undergo chemotherapy for a solid tumor might have an increased risk developing febrile neutropenia (FN). We investigated in a prospective cohort study relations between MBL-serum levels and polymorphisms in MBL promotor genotypes (-550H/L and -221X/Y) on incidence and severity of FN. Risk of FN was 17.9% in MBL-deficient and 22.5% in MBL-sufficient patients (RR = 0.796, p = 0.45). Median MBL serum levels at baseline were respectively 1.39 µg/mL and 1.09 µg/mL (p = 0.92) in patients with and without FN. In conclusion, serum MBL and MBL genotypes (-550H/L and -221X/Y) do not determine the risk for developing FN.


Asunto(s)
Neutropenia Febril Inducida por Quimioterapia/genética , Lectina de Unión a Manosa/genética , Neoplasias/genética , Polimorfismo Genético , Regiones Promotoras Genéticas/genética , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neutropenia Febril Inducida por Quimioterapia/sangre , Femenino , Genotipo , Humanos , Masculino , Lectina de Unión a Manosa/sangre , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/tratamiento farmacológico , Pronóstico , Estudios Prospectivos , Factores de Riesgo
9.
Biochem Med (Zagreb) ; 29(1): 010702, 2019 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-30591812

RESUMEN

INTRODUCTION: Cancer patients with chemotherapy-induced febrile neutropenia are a heterogeneous group with a significant risk of serious medical complications. In these patients, the Multinational Association for Supportive Care in Cancer (MASCC) score is the most widely used tool for risk-stratification. The aim of this prospective study was to analyse the value of procalcitonin (PCT) and lipopolysaccharide binding protein (LBP) to predict serious complications and bacteraemia in cancer patients with febrile neutropenia, compared with MASCC score. MATERIALS AND METHODS: Data were collected from 111 episodes of febrile neutropenia admitted consecutively to the emergency department. In all of them, MASCC score was calculated and serum samples were collected for measurement of PCT and LBP by well-established methods. The main and secondary outcomes were the development of serious complications and bacteraemia, respectively. RESULTS: A serious complication occurred in 20 (18%) episodes and in 16 (14%) bacteraemia was detected. Areas under the receiver operating characteristic curve (ROC AUC) of MASCC score, PCT and LBP to select low-risk patients were 0.83 (95% confidence interval (CI): 0.74 - 0.89), 0.85 (95% CI: 0.77 - 0.91) and 0.70 (95% CI: 0.61 - 0.78), respectively. For bacteraemia, MASCC score, PCT and LBP showed ROC AUCs of 0.74 (95% CI: 0.64 - 0.82), 0.86 (95% CI: 0.78 - 0.92) and 0.76 (95% CI: 0.67 - 0.83), respectively. CONCLUSION: A single measurement of PCT performs similarly as MASCC score to predict serious medical complications in cancer patients with febrile neutropenia and can be a useful tool for risk stratification. Besides, low PCT concentrations can be used to rule-out the presence of bacteraemia.


Asunto(s)
Proteínas Portadoras/sangre , Neutropenia Febril Inducida por Quimioterapia/diagnóstico , Servicio de Urgencia en Hospital , Glicoproteínas de Membrana/sangre , Neoplasias/diagnóstico , Polipéptido alfa Relacionado con Calcitonina/sangre , Proteínas de Fase Aguda , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos , Neutropenia Febril Inducida por Quimioterapia/sangre , Neutropenia Febril Inducida por Quimioterapia/tratamiento farmacológico , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/tratamiento farmacológico , Pronóstico , Estudios Prospectivos , Adulto Joven
10.
Support Care Cancer ; 26(11): 3819-3826, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29777383

RESUMEN

PURPOSE: Only a third of children with cancer and febrile neutropenia (FN) have a proven bacterial infection; nevertheless, most children are hospitalized and treated with intravenous antibiotics. Several biomarkers have been proposed as predictive markers for bacterial infection in this population. We aimed to evaluate the role of interleukin-6 (IL-6) and procalcitonin (PCT) in diagnosing bacterial infection in children with cancer and FN. METHODS: The study population was derived from a prospective database (2006-2013, IL-8 study) comprising children with cancer who presented with FN. From stored plasma samples (taken at admission and/or at 12-24 h), we determined the PCT and IL-6 levels. Consequently, we explored their relation with the presence of bacterial infection (positive blood culture, radiologically documented infection or clinical bacterial focus). We predefined cutoff values at 60 ng/L for IL-6 and 0.25 ng/mL for PCT. RESULTS: Seventy-seven FN episodes in 55 children with cancer were included. In 18 episodes (23.4%), a bacterial infection was documented. Both at presentation and after 12-24 h, median values of IL-6 and PCT were significantly higher in patients with a bacterial infection compared to patients without a bacterial infection. With both biomarkers above cutoff values, sensitivity was 93% (with either one, this was even 100%). The identified group at low risk for bacterial infection comprised 41% of the population. CONCLUSION: PCT and IL-6 are promising markers in identifying bacterial infection in children with cancer and FN. In a subsequent project, we will incorporate these biomarkers in a risk assessment model that we will test prospectively in a clinical trial.


Asunto(s)
Calcitonina/sangre , Neutropenia Febril Inducida por Quimioterapia/sangre , Neutropenia Febril Inducida por Quimioterapia/diagnóstico , Interleucina-6/sangre , Neoplasias/sangre , Adolescente , Infecciones Bacterianas/sangre , Infecciones Bacterianas/complicaciones , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/epidemiología , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Calcitonina/análisis , Neutropenia Febril Inducida por Quimioterapia/epidemiología , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Interleucina-6/análisis , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/epidemiología , Países Bajos/epidemiología , Valor Predictivo de las Pruebas , Precursores de Proteínas/análisis , Precursores de Proteínas/sangre , Medición de Riesgo
11.
J Infect Chemother ; 24(7): 544-548, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29627326

RESUMEN

A central venous catheter (CVC) is a catheter placed into a large vein, and is used for chemotherapy administration. However, there is little confirmatory data on which antiseptic-such as chlorhexidine or povidone-iodine (PI) -is more protective against CVC-related infectious complications in patients receiving intensive chemotherapy. We aimed to compare the effectiveness of 1% chlorhexidine gluconate in 70% alcohol (CH) vs. PI for skin disinfection before CVC insertion in patients receiving intensive chemotherapy. Methods We used either CH or 10% PI as skin antiseptics before CVC insertion, and assessed which agent was more protective against CVC-related infection. The participants were 112 patients with haematologic malignancies who underwent chemotherapy; a total of 292 CVCs were inserted over this period. Blood cultures were obtained when febrile neutropenia occurred. The CVC was removed and the catheter-tip qualitatively cultured when catheter-related infection was suspected. The cumulative incidence of febrile neutropenia, microbial growth from blood or catheter-tip culture, and catheter-related blood stream infection (CRBSI) was evaluated retrospectively. A univariate Cox proportional hazards model showed that CH significantly alleviated infectious complications. Notably, no case of CRBSI occurred in the CH group. Multivariate analysis, adjusted for prolonged neutropenia (>15 days) and older age (>52 years), also showed significant reduction in the cumulative incidence of microbial growth from catheter-tips in the CH group (hazard ratio = 0.146, 95% confidence interval: 0.023-0.502, p = 0.0008). Disinfection using CH, compared with PI, can potentially decrease catheter-related infection without causing adverse skin reactions in patients with haematologic malignancies.


Asunto(s)
Antiinfecciosos Locales/uso terapéutico , Infecciones Relacionadas con Catéteres/tratamiento farmacológico , Infecciones Relacionadas con Catéteres/prevención & control , Catéteres Venosos Centrales/microbiología , Clorhexidina/análogos & derivados , Neoplasias Hematológicas/tratamiento farmacológico , Adolescente , Adulto , Anciano , Cateterismo Venoso Central , Catéteres Venosos Centrales/efectos adversos , Neutropenia Febril Inducida por Quimioterapia/sangre , Neutropenia Febril Inducida por Quimioterapia/microbiología , Clorhexidina/uso terapéutico , Desinfección/métodos , Contaminación de Equipos , Etanol , Femenino , Humanos , Masculino , Persona de Mediana Edad , Povidona Yodada/uso terapéutico , Estudios Retrospectivos , Piel/microbiología
12.
J Cancer Res Clin Oncol ; 144(6): 1087-1095, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29671069

RESUMEN

PURPOSE: Pegfilgrastim is a long-acting granulocyte colony-stimulating factor indicated for prevention of febrile neutropenia in patients receiving myelosuppressive chemotherapy by promoting neutrophil recovery. METHODS: This phase 1, randomized, double-blind, three-way crossover trial in healthy volunteers evaluated the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of the proposed biosimilar, comparing MYL-1401H, reference pegfilgrastim (Neulasta®, Amgen Inc, Thousand Oaks, CA, USA) sourced from the European Union, and reference pegfilgrastim sourced from the USA. Primary PK end points were peak plasma concentration of pegfilgrastim (Cmax) and area under the plasma concentration-time curve from the time of dosing to infinity (AUC0-inf). Primary PD end points were area under the curve above baseline for absolute neutrophil counts (ANC AUC0-t) and maximum change from baseline for ANC (ANC Cmax). Adverse events were also recorded. RESULTS: The primary PK and PD end points were similar across all groups. For the PK parameters, the 90% confidence intervals (CIs) of the ratios of geometric means ranged between 0.91 and 1.18, which were within the predefined bioequivalence interval of 0.8000 to 1.2500 for all comparisons. For the PD parameters, the 95% CIs of the ratios of geometric means ranged between 0.94 and 1.06 for all comparisons, which were within the predefined PD equivalence interval of 0.8500 to 1.1765. The safety profiles were similar, with the most common adverse events being back pain and headache. CONCLUSIONS: MYL-1401H demonstrated similar PK, PD, and safety to reference pegfilgrastim in healthy volunteers and may be an equivalent option for the prevention of febrile neutropenia.


Asunto(s)
Biosimilares Farmacéuticos/farmacología , Biosimilares Farmacéuticos/farmacocinética , Filgrastim/farmacología , Filgrastim/farmacocinética , Polietilenglicoles/farmacología , Polietilenglicoles/farmacocinética , Adulto , Biosimilares Farmacéuticos/efectos adversos , Neutropenia Febril Inducida por Quimioterapia/sangre , Neutropenia Febril Inducida por Quimioterapia/etiología , Estudios Cruzados , Método Doble Ciego , Femenino , Filgrastim/efectos adversos , Humanos , Masculino , Polietilenglicoles/efectos adversos , Equivalencia Terapéutica
13.
Pediatr Blood Cancer ; 65(3)2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29115709

RESUMEN

BACKGROUND: Febrile neutropenia (F&N) is common among pediatric oncology patients. However, there is a lack of clarity regarding parameters whereby such patients have demonstrated adequate bone marrow recovery for hospital discharge and empiric antibiotic discontinuation. PROCEDURE: A retrospective review was performed for 350 episodes of F&N occurring at a single institution between 2007 and 2012 in pediatric oncology patients who were afebrile for 24 hr and had no bacterial source identified. Seven-day postdischarge outcomes were assessed and compared based on absolute neutrophil count (ANC) at discharge in order to identify an optimal threshold. RESULTS: Overall, 7-day readmission rates were low (17/350, 4.6%), with patients discharged with post-nadir ANC of 100-199/µl (2/51, 3.9%), 200-499/µl (5/125, 4.0%), and ≥500/µl (8/160, 5.0%), all having similar rates. Patients with a discharge ANC < 100/µl (2/14, 14.3%) had a higher readmission rate. A new bloodstream infection was identified upon readmission in one patient in each discharge ANC range except for ANC of 100-199/µl, in which none occurred. In a subset of 217 episodes where the ANC fell below 200/µl during the admission and subsequently rose above 100/µl, 94 episodes resulted in 126 additional hospital days while subjects awaited further count recovery. One death occurred in a patient whose ANC at discharge was 290/µl. This patient had received additional chemotherapy after count recovery and prior to discharge, and was readmitted with Clostridium tertium bacteremia. CONCLUSION: These results suggest that a post-nadir ANC > 100/µl is a safe threshold value for empiric antibiotic discontinuation and discharge home.


Asunto(s)
Biomarcadores/sangre , Neutropenia Febril Inducida por Quimioterapia/sangre , Neutrófilos , Antibacterianos/uso terapéutico , Médula Ósea , Células de la Médula Ósea/citología , Neutropenia Febril Inducida por Quimioterapia/tratamiento farmacológico , Niño , Preescolar , Femenino , Humanos , Recuento de Leucocitos , Masculino , Neoplasias/tratamiento farmacológico , Alta del Paciente , Estudios Retrospectivos
14.
Hematology Am Soc Hematol Educ Program ; 2017(1): 187-193, 2017 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-29222255

RESUMEN

Non-chemotherapy idiosyncratic drug-induced neutropenia (IDIN) is a relatively rare but potentially fatal disorder that occurs in susceptible individuals, with an incidence of 2.4 to 15.4 cases per million population. Affected patients typically experience severe neutropenia within several weeks to several months after first exposure to a drug, and mortality is ∼5%. The drugs most frequently associated with IDIN include metamizole, clozapine, sulfasalazine, thiamazole, carbimazole, amoxicillin, cotrimoxazole, ticlopidine, and valganciclovir. The idiosyncratic nature of IDIN, the lack of mouse models and diagnostic testing, and its low overall incidence make rigorous studies to elucidate possible mechanisms exceptionally difficult. An immune mechanism for IDIN involving neutrophil destruction by hapten (drug)-specific antibodies and drug-induced autoantibodies is frequently suggested, but strong supporting evidence is lacking. Although laboratory testing for neutrophil drug-dependent antibodies is rarely performed because of the complexity and low sensitivity of tests currently in use, these assays could possibly be enhanced by using reactive drug metabolites in place of the parent drug. Patients typically experience acute, severe neutropenia, or agranulocytosis (<0.5 × 109 neutrophils/L) and symptoms of fever, chills, sore throat, and muscle and joint pain. Diagnosis can be difficult, but timely recognition is critical because if left untreated, there is an increase in mortality. Expanded studies of the production and mechanistic role of reactive drug metabolites, genetic associations, and improved animal models of IDIN are essential to further our understanding of this important disorder.


Asunto(s)
Neutropenia Febril Inducida por Quimioterapia/sangre , Neutropenia Febril Inducida por Quimioterapia/diagnóstico , Neutropenia Febril Inducida por Quimioterapia/epidemiología , Neutropenia Febril Inducida por Quimioterapia/terapia , Animales , Humanos , Incidencia , Ratones
15.
Transpl Infect Dis ; 19(6)2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28746781

RESUMEN

We report a case of human herpesvirus-6 (HHV-6) encephalitis in a neutropenic patient who had undergone chemotherapy induction for acute myelogenous leukemia while on broad-spectrum antimicrobial therapy. The patient displayed symptoms of confusion, amnesia, and lethargy. Diagnosis was made via polymerase chain reaction analysis of cerebrospinal fluid. Electroencephalogram and magnetic resonance imaging of the brain were unremarkable. Following diagnosis, the patient was successfully treated with ganciclovir. HHV-6 encephalitis should be considered in immunocompromised patients who become encephalopathic.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Encefalitis Viral/diagnóstico , Quimioterapia de Inducción/efectos adversos , Leucemia Mieloide Aguda/tratamiento farmacológico , Infecciones por Roseolovirus/diagnóstico , Anciano , Antiinfecciosos/uso terapéutico , Biopsia , Médula Ósea/patología , Encéfalo/diagnóstico por imagen , Neutropenia Febril Inducida por Quimioterapia/sangre , Neutropenia Febril Inducida por Quimioterapia/microbiología , Neutropenia Febril Inducida por Quimioterapia/terapia , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/terapia , Electroencefalografía , Encefalitis Viral/líquido cefalorraquídeo , Encefalitis Viral/tratamiento farmacológico , Encefalitis Viral/virología , Herpesvirus Humano 6/aislamiento & purificación , Humanos , Huésped Inmunocomprometido , Quimioterapia de Inducción/métodos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patología , Imagen por Resonancia Magnética , Masculino , Pancitopenia/sangre , Pancitopenia/diagnóstico , Infecciones por Roseolovirus/líquido cefalorraquídeo , Infecciones por Roseolovirus/tratamiento farmacológico , Infecciones por Roseolovirus/virología , Tomografía Computarizada por Rayos X
16.
J Infect Chemother ; 23(11): 788-790, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28743428

RESUMEN

Antibiotic-resistant infections remain to be a major issue for all over the world. Although appropriate diagnosis and rapid treatment initiation are crucially important particularly in immunocompromised patients, selection of antibiotics without identification of causative bacteria is often challenging. A 44-year-old woman with acute myeloid leukemia (AML) under myelosuppression suffered from teicoplanin-resistant gram-positive cocci bacteremia. Taking severe neutropenia due to chemotherapy and glycopeptide-resistance into account, teicoplanin was empirically substituted with daptomycin, which led to prompt defervescence. This microorganism later turned out to be Leuconostoc lactis (L. Lactis), and daptmycin was continued to use based on antimicrobial susceptibility tests. As a result, empiric use of daptomycin successfully controlled glycopeptide-resistant gram-positive cocci bacteremia under neutropenia. This is the first report of daptomycin treatment for L. lactis bacteremia in a patient with AML under neutropenia. Our findings suggest that daptomycin would be a suitable treatment option for glycopeptide-resistant gram-positive cocci bloodstream infections, especially in myelosuppressive patients.


Asunto(s)
Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Neutropenia Febril Inducida por Quimioterapia/tratamiento farmacológico , Enterococcus/efectos de los fármacos , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Inmunosupresores/efectos adversos , Leuconostoc/efectos de los fármacos , Leucemia Mieloide Aguda/tratamiento farmacológico , Adulto , Antibacterianos/farmacología , Bacteriemia/sangre , Bacteriemia/microbiología , Neutropenia Febril Inducida por Quimioterapia/sangre , Neutropenia Febril Inducida por Quimioterapia/microbiología , Daptomicina/farmacología , Daptomicina/uso terapéutico , Farmacorresistencia Bacteriana , Enterococcus/aislamiento & purificación , Enterococcus/patogenicidad , Enterococcus/fisiología , Femenino , Infecciones por Bacterias Grampositivas/sangre , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Huésped Inmunocomprometido , Leuconostoc/aislamiento & purificación , Leuconostoc/patogenicidad , Leuconostoc/fisiología , Pruebas de Sensibilidad Microbiana , Teicoplanina/farmacología , Teicoplanina/uso terapéutico , Vancomicina/uso terapéutico
17.
Br J Clin Pharmacol ; 83(11): 2416-2425, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28640540

RESUMEN

AIM: α1 -Acid glycoprotein (AAG), which is a major binding protein of docetaxel, is considered to be a determinant for docetaxel pharmacokinetics. However, there are no reports about the impact of serum AAG on pharmacokinetics and pharmacodynamics in elderly patients treated with docetaxel. The aim of this prospective study was to elucidate the effects of advanced age and serum AAG on docetaxel unbound exposure and neutropenia, dose-limiting toxicity, in cancer patients. METHODS: Docetaxel was administered at 60 mg m-2 to 51 patients with non-small cell lung cancer, 17 of whom were ≥75 years of age. Pharmacokinetics, unbound fraction (fu), neutropenia, serum protein levels of AAG and albumin, as well as baseline absolute neutrophil count (ANC) were assessed during the first course. Population pharmacokinetic and pharmacodynamic analyses were performed to evaluate the influence of clinically relevant factors on docetaxel pharmacokinetics and neutropenia. RESULTS: Clearance of docetaxel and degree of fu were significantly associated with serum AAG level, but not with age. Area under the concentration-time curve of unbound docetaxel (fu·AUC) was significantly higher in patients aged ≥75 years (0.389 µg·h ml-1 , 95% CI; 0.329-0.448 µg·h ml-1 ) compared with patients aged <75 years (0.310 µg·h ml-1 , 95% CI; 0.268-0.352 µg·h ml-1 ). Percent decrease in ANC at nadir related to fu·AUC, and was dependent on baseline ANC. CONCLUSION: Regardless of ageing, serum level of AAG determines docetaxel unbound exposure and related dose-limiting toxicity. Serum AAG level and ANC at baseline appear to be predictive of neutropenia for patients of all ages following the administration of docetaxel.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Orosomucoide/análisis , Taxoides/farmacología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antineoplásicos Fitogénicos/uso terapéutico , Área Bajo la Curva , Carcinoma de Pulmón de Células no Pequeñas/sangre , Neutropenia Febril Inducida por Quimioterapia/sangre , Neutropenia Febril Inducida por Quimioterapia/epidemiología , Neutropenia Febril Inducida por Quimioterapia/etiología , Docetaxel , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Neoplasias Pulmonares/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Taxoides/uso terapéutico
18.
J Obstet Gynaecol Res ; 43(4): 758-762, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28418211

RESUMEN

AIM: The aim of this study was to evaluate whether frequency of complete blood count (CBC) testing during chemotherapy for gynecologic cancer impacts hospital admissions or rates of neutropenic fever. METHODS: A retrospective cohort study was performed at a single academic institution. Patients undergoing platinum-based chemotherapy for endometrial or ovarian cancer from January 2010 to December 2014 were identified from a clinical database. Patients receiving dose-dense chemotherapy or on a clinical trial were excluded. Electronic chart review collected demographic and clinical characteristics. The primary outcome was the rate of febrile neutropenia or hospital admission. RESULTS: A total of 174 patients were identified, 63 (36%) with endometrial and 111 (64%) with ovarian cancer. Fifty-four percent of patients received multiple CBC per cycle compared with 46% who only had one CBC per cycle. The majority of patients were treated with a platinum-based doublet (85%). Dose reductions, addition of granulocyte colony stimulating factor, and rates of grade 3 or 4 anemia and neutropenia were significantly associated with more frequent testing. There was no difference in rates of neutropenic fever (5.3 vs 3.8%, P = 0.45) or hospital admission (22.3 vs 21.3%, P = 0.86) for multiple versus single CBC monitoring. CONCLUSION: More frequent laboratory testing detected more cases of grade 3 or 4 hematopoietic toxicities and was associated with more interventions. There were no differences in number of hospitalizations or cases of neutropenic fever by frequency of laboratory testing, suggesting that it may be appropriate to decrease routine laboratory tests for select patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Recuento de Células Sanguíneas/economía , Recuento de Células Sanguíneas/normas , Neutropenia Febril Inducida por Quimioterapia/sangre , Neoplasias Endometriales/tratamiento farmacológico , Hospitalización/economía , Neoplasias Ováricas/tratamiento farmacológico , Platino (Metal)/toxicidad , Anciano , Neutropenia Febril Inducida por Quimioterapia/economía , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos
19.
J Clin Lab Anal ; 31(6)2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28133789

RESUMEN

INTRODUCTION: Infections represent a major complication of hematological malignancies. C-reactive protein (CRP) and procalcitonin (PCT) have been used as diagnostic biomarkers of infections, but do not produce definitive findings. Recently, a new biomarker, presepsin, has been used as a diagnostic tool for detecting infections in the fields of emergency and neonatal medicine. However, the usefulness of presepsin for identifying infections in patients with hematological malignancies, including those who develop febrile neutropenia, remains unclear. METHODS: In this study, we retrospectively analyzed the utility of PCT, presepsin, and CRP as biomarkers of infections during 49 febrile episodes that occurred in 28 patients with hematological malignancies. RESULTS: The levels of PCT, but not those of CRP or presepsin, were significantly higher in the infection group than in the uninfected group (P<.03), indicating that PCT might be a more sensitive biomarker of infections. No differences in presepsin levels were detected between the patients with and without neutropenia, or between the infected and uninfected patients with neutropenia, indicating that presepsin might have less diagnostic value in patients with neutropenia. CONCLUSIONS: We conclude that PCT might provide additional information and could be used in combination with other biomarkers to detect infections in patients with hematological malignancies.


Asunto(s)
Proteína C-Reactiva/análisis , Calcitonina/sangre , Neutropenia Febril Inducida por Quimioterapia/diagnóstico , Neoplasias Hematológicas , Infecciones/diagnóstico , Receptores de Lipopolisacáridos/sangre , Fragmentos de Péptidos/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Neutropenia Febril Inducida por Quimioterapia/sangre , Neutropenia Febril Inducida por Quimioterapia/epidemiología , Femenino , Neoplasias Hematológicas/sangre , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/epidemiología , Humanos , Infecciones/sangre , Infecciones/epidemiología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Estudios Retrospectivos , Adulto Joven
20.
Pediatr Blood Cancer ; 64(6)2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-27860223

RESUMEN

PURPOSE: The study aims to validate a score predicting risk of complications in pediatric patients with chemotherapy-related febrile neutropenia (FN) and evaluate the performance of previously published models for risk stratification. PATIENTS AND METHODS: Children diagnosed with cancer and presenting with FN were evaluated in a prospective single-center study. A score predicting the risk of complications, previously derived in the unit, was validated on a prospective cohort. Performance of six predictive models published from geographically distinct settings was assessed on the same cohort. RESULTS: Complications were observed in 109 (26.3%) of 414 episodes of FN over 15 months. A risk score based on undernutrition (two points), time from last chemotherapy (<7 days = two points), presence of a nonupper respiratory focus of infection (two points), C-reactive protein (>60 mg/l = five points), and absolute neutrophil count (<100 per µl = two points) was used to stratify patients into "low risk" (score <7, n = 208) and assessed using the following parameters: overall performance (Nagelkerke R2 = 34.4%), calibration (calibration slope = 0.39; P = 0.25 in Hosmer-Lemeshow test), discrimination (c-statistic = 0.81), overall sensitivity (86%), negative predictive value (93%), and clinical net benefit (0.43). Six previously published rules demonstrated inferior performance in this cohort. CONCLUSION: An indigenous decision rule using five simple predefined variables was successful in identifying children at risk for complications. Prediction models derived in developed nations may not be appropriate for low-middle-income settings and need to be validated before use.


Asunto(s)
Neutropenia Febril Inducida por Quimioterapia/epidemiología , Modelos Biológicos , Neoplasias/tratamiento farmacológico , Neoplasias/epidemiología , Proteína C-Reactiva/metabolismo , Neutropenia Febril Inducida por Quimioterapia/sangre , Niño , Preescolar , Femenino , Humanos , Recuento de Leucocitos , Masculino , Neoplasias/sangre , Estudios Prospectivos , Infecciones del Sistema Respiratorio/sangre , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/etiología , Factores de Riesgo
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