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1.
Future Oncol ; 15(9): 1021-1034, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30757910

RESUMEN

AIM: To evaluate treatment patterns of diffuse large B-cell lymphoma (DLBCL). PATIENTS & METHODS: First-line and relapsed/refractory treatment patterns and survival outcomes following first-line therapy in adult patients newly diagnosed with DLBCL were evaluated. RESULTS: A total of 1436 DLBCL patients initiated treatment and mainly received a combination regimen versus monotherapy (92.1 vs 7.9%). Patients who received monotherapy were older with more comorbidities and had shorter progression-free survival than patients receiving combination therapy (median: 31.3 vs 55.8 months). In the second-line setting (n = 164), rituximab-based combination regimens were most common; 25% underwent stem cell transplantation, and were younger with fewer comorbidities. CONCLUSION: These results illustrate the need for new treatment options for patients unable to tolerate initial combination therapy and transplant-ineligible patients who require salvage therapy.


Asunto(s)
Linfoma de Células B Grandes Difuso/terapia , Recurrencia Local de Neoplasia/terapia , Pautas de la Práctica en Medicina/estadística & datos numéricos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bases de Datos Factuales/estadística & datos numéricos , Resistencia a Antineoplásicos , Registros Electrónicos de Salud/estadística & datos numéricos , Femenino , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Supervivencia sin Progresión , Inducción de Remisión/métodos , Estudios Retrospectivos , Rituximab/uso terapéutico , Terapia Recuperativa/métodos , Terapia Recuperativa/estadística & datos numéricos , Trasplante de Células Madre/estadística & datos numéricos , Análisis de Supervivencia , Estados Unidos/epidemiología , Adulto Joven
2.
Future Oncol ; 14(25): 2627-2642, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29911900

RESUMEN

AIM: Evaluate healthcare costs and utilization of treated diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) patients. MATERIALS & METHODS: Adults with newly diagnosed DLBCL and FL between 1 January 2008 and 31 October 2015 were identified in the Optum™ claims database. Healthcare costs and utilization were assessed from diagnosis date until end of follow-up. RESULTS: A total of 1267 DLBCL- and 1595 FL-treated patients were identified. Mean per-patient, per-month cost during follow-up was US$11,890 for DLBCL and US$10,460 for FL. Healthcare costs and utilization decreased from year 1 to 2 following diagnosis, due to a decrease in chemotherapy services, inpatient admissions and other outpatient services. CONCLUSION: The economic burden of treated DLBCL and FL is considerable, especially in the first year following diagnosis.


Asunto(s)
Costo de Enfermedad , Linfoma Folicular/economía , Linfoma de Células B Grandes Difuso/economía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Costos de la Atención en Salud , Humanos , Pacientes Internos , Linfoma Folicular/terapia , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estados Unidos , Adulto Joven
3.
Lancet ; 387(10020): 760-9, 2016 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-26684607

RESUMEN

BACKGROUND: Isavuconazole is a novel triazole with broad-spectrum antifungal activity. The SECURE trial assessed efficacy and safety of isavuconazole versus voriconazole in patients with invasive mould disease. METHODS: This was a phase 3, double-blind, global multicentre, comparative-group study. Patients with suspected invasive mould disease were randomised in a 1:1 ratio using an interactive voice-web response system, stratified by geographical region, allogeneic haemopoietic stem cell transplantation, and active malignant disease at baseline, to receive isavuconazonium sulfate 372 mg (prodrug; equivalent to 200 mg isavuconazole; intravenously three times a day on days 1 and 2, then either intravenously or orally once daily) or voriconazole (6 mg/kg intravenously twice daily on day 1, 4 mg/kg intravenously twice daily on day 2, then intravenously 4 mg/kg twice daily or orally 200 mg twice daily from day 3 onwards). We tested non-inferiority of the primary efficacy endpoint of all-cause mortality from first dose of study drug to day 42 in patients who received at least one dose of the study drug (intention-to-treat [ITT] population) using a 10% non-inferiority margin. Safety was assessed in patients who received the first dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00412893. FINDINGS: 527 adult patients were randomly assigned (258 received study medication per group) between March 7, 2007, and March 28, 2013. All-cause mortality from first dose of study drug to day 42 for the ITT population was 19% with isavuconazole (48 patients) and 20% with voriconazole (52 patients), with an adjusted treatment difference of -1·0% (95% CI -7·8 to 5·7). Because the upper bound of the 95% CI (5·7%) did not exceed 10%, non-inferiority was shown. Most patients (247 [96%] receiving isavuconazole and 255 [98%] receiving voriconazole) had treatment-emergent adverse events (p=0·122); the most common were gastrointestinal disorders (174 [68%] vs 180 [69%]) and infections and infestations (152 [59%] vs 158 [61%]). Proportions of patients with treatment-emergent adverse events by system organ class were similar overall. However, isavuconazole-treated patients had a lower frequency of hepatobiliary disorders (23 [9%] vs 42 [16%]; p=0·016), eye disorders (39 [15%] vs 69 [27%]; p=0·002), and skin or subcutaneous tissue disorders (86 [33%] vs 110 [42%]; p=0·037). Drug-related adverse events were reported in 109 (42%) patients receiving isavuconazole and 155 (60%) receiving voriconazole (p<0·001). INTERPRETATION: Isavuconazole was non-inferior to voriconazole for the primary treatment of suspected invasive mould disease. Isavuconazole was well tolerated compared with voriconazole, with fewer study-drug-related adverse events. Our results support the use of isavuconazole for the primary treatment of patients with invasive mould disease. FUNDING: Astellas Pharma Global Development, Basilea Pharmaceutica International.


Asunto(s)
Antifúngicos/uso terapéutico , Micosis/tratamiento farmacológico , Nitrilos/uso terapéutico , Piridinas/uso terapéutico , Triazoles/uso terapéutico , Voriconazol/uso terapéutico , Administración Oral , Adulto , Anciano , Antifúngicos/administración & dosificación , Antifúngicos/efectos adversos , Aspergilosis/tratamiento farmacológico , Aspergilosis/mortalidad , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Micosis/mortalidad , Nitrilos/administración & dosificación , Nitrilos/efectos adversos , Piridinas/administración & dosificación , Piridinas/efectos adversos , Resultado del Tratamiento , Triazoles/administración & dosificación , Triazoles/efectos adversos , Voriconazol/administración & dosificación , Voriconazol/efectos adversos
4.
Clin Infect Dis ; 63(4): e1-e60, 2016 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-27365388

RESUMEN

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.


Asunto(s)
Antifúngicos/uso terapéutico , Aspergilosis/diagnóstico , Anfotericina B/uso terapéutico , Aspergilosis/tratamiento farmacológico , Aspergilosis/epidemiología , Azoles/uso terapéutico , Equinocandinas/uso terapéutico , Humanos , Infectología/organización & administración , Sociedades Médicas , Estados Unidos
5.
Clin Infect Dis ; 63(4): 433-42, 2016 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-27481947

RESUMEN

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.


Asunto(s)
Antifúngicos/uso terapéutico , Aspergilosis/diagnóstico , Guías de Práctica Clínica como Asunto/normas , Anfotericina B/uso terapéutico , Aspergilosis/tratamiento farmacológico , Aspergilosis/epidemiología , Azoles/uso terapéutico , Equinocandinas/uso terapéutico , Humanos , Infectología/organización & administración , Sociedades Médicas , Estados Unidos
6.
Am J Hematol ; 91(2): 179-84, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26492520

RESUMEN

We recently defined event-free survival at 24 months (EFS24) as a clinically relevant outcome for patients with DLBCL. Patients who fail EFS24 have very poor overall survival, while those who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. Here, we develop and validate a clinical risk calculator (IPI24) for EFS24. Model building was performed on a discovery dataset of 1,348 patients with DLBCL and treated with anthracycline-based immunochemotherapy. A multivariable model containing age, Ann Arbor stage, normalized serum LDH, ALC, ECOG performance status, bulky disease, and sex was identified. The model was then applied to an independent validation dataset of 1,177 DLBCL patients. The IPI24 score estimates the probability of failing to achieve the EFS24 endpoint for an individual patient. The IPI24 model showed superior discriminatory ability (c-statistic = 0.671) in the validation dataset compared to the IPI (c-statistic = 0.649) or the NCCN-IPI (c-statistic = 0.657). After recalibration of the model on the combined dataset, the median predicted probability of failing to achieve EFS24 was 36% (range, 12-88%), and the IPI24 showed an EFS24 gradient in all IPI groups. The IPI24 also identified a significant percentage of patients with high risk disease, with over 20% of patients having a 50% or higher risk of failing to achieve EFS24. The IPI24 provides an individual patient level probability of achieving the clinically relevant EFS24 endpoint. It can be used via electronic apps.


Asunto(s)
Linfoma de Células B Grandes Difuso/mortalidad , Modelos Estadísticos , Medicina de Precisión , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunoterapia/métodos , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Factores de Riesgo , Adulto Joven
7.
Clin Infect Dis ; 60(6): 900-9, 2015 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-25416754

RESUMEN

BACKGROUND: The Shingles Prevention Study (SPS) demonstrated zoster vaccine efficacy through 4 years postvaccination. A Short-Term Persistence Substudy (STPS) demonstrated persistence of vaccine efficacy for at least 5 years. A Long-Term Persistence Substudy (LTPS) was undertaken to further assess vaccine efficacy in SPS vaccine recipients followed for up to 11 years postvaccination. Study outcomes were assessed for the entire LTPS period and for each year from 7 to 11 years postvaccination. METHODS: Surveillance, case determination, and follow-up were comparable to those in SPS and STPS. Because SPS placebo recipients were offered zoster vaccine before the LTPS began, there were no unvaccinated controls. Instead, SPS and STPS placebo results were used to model reference placebo groups. RESULTS: The LTPS enrolled 6867 SPS vaccine recipients. Compared to SPS, estimated vaccine efficacy in LTPS decreased from 61.1% to 37.3% for the herpes zoster (HZ) burden of illness (BOI), from 66.5% to 35.4% for incidence of postherpetic neuralgia, and from 51.3% to 21.1% for incidence of HZ, and declined for all 3 outcome measures from 7 through 11 years postvaccination. Vaccine efficacy for the HZ BOI was significantly greater than zero through year 10 postvaccination, whereas vaccine efficacy for incidence of HZ was significantly greater than zero only through year 8. CONCLUSIONS: Estimates of vaccine efficacy decreased over time in the LTPS population compared with modeled control estimates. Statistically significant vaccine efficacy for HZ BOI persisted into year 10 postvaccination, whereas statistically significant vaccine efficacy for incidence of HZ persisted only through year 8.


Asunto(s)
Vacuna contra el Herpes Zóster , Herpes Zóster/prevención & control , Anciano , Anciano de 80 o más Años , Costo de Enfermedad , Monitoreo Epidemiológico , Femenino , Estudios de Seguimiento , Herpes Zóster/complicaciones , Herpes Zóster/epidemiología , Vacuna contra el Herpes Zóster/efectos adversos , Vacuna contra el Herpes Zóster/inmunología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neuralgia Posherpética/epidemiología , Neuralgia Posherpética/prevención & control , Vacunación , Potencia de la Vacuna
8.
Clin Infect Dis ; 59 Suppl 5: S360-4, 2014 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-25352632

RESUMEN

The introduction of novel agents to the therapeutic armamentarium for oncologic, rheumatologic, and neurologic disorders has resulted in major clinical advances. These agents impact immune function, resulting in a discrete spectrum of infectious complications. Purine analogues and alemtuzumab alter cell-mediated immunity, resulting in opportunistic viral/fungal infections. Herpes zoster incidence increases with bortezomib. Hepatitis B reactivation may occur with rituximab. Cases of progressive multifocal leukoencephalopathy have occurred following monoclonal antibody therapy. Tumor necrosis factor-α inhibitor therapy is complicated by tuberculosis reactivation and fungal infections. We summarize the impact of these therapies on pathogenesis and spectrum of infection complicating their usage.


Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/efectos adversos , Neoplasias/complicaciones , Infecciones Oportunistas/inmunología , Anciano , Infecciones Bacterianas/inmunología , Infecciones Bacterianas/microbiología , Ácidos Borónicos/efectos adversos , Bortezomib , Femenino , Humanos , Tolerancia Inmunológica , Masculino , Persona de Mediana Edad , Micosis/inmunología , Micosis/microbiología , Pirazinas/efectos adversos , Factor de Necrosis Tumoral alfa/efectos adversos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Virosis/inmunología , Virosis/virología
9.
Blood ; 120(4): 843-6, 2012 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-22700719

RESUMEN

We performed a meta-analysis of 3 genome-wide association studies to identify additional common variants influencing chronic lymphocytic leukemia (CLL) risk. The discovery phase was composed of genome-wide association study data from 1121 cases and 3745 controls. Replication analysis was performed in 861 cases and 2033 controls. We identified a novel CLL risk locus at 6p21.33 (rs210142; intronic to the BAK1 gene, BCL2 antagonist killer 1; P = 9.47 × 10(-16)). A strong relationship between risk genotype and reduced BAK1 expression was shown in lymphoblastoid cell lines. This finding provides additional support for polygenic inheritance to CLL and provides further insight into the biologic basis of disease development.


Asunto(s)
Antineoplásicos/efectos adversos , Aberraciones Cromosómicas/inducido químicamente , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Leucemia Mieloide de Fase Crónica/genética , Cromosoma Filadelfia , Piperazinas/efectos adversos , Pirimidinas/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Benzamidas , Análisis Citogenético , Femenino , Humanos , Mesilato de Imatinib , Hibridación Fluorescente in Situ , Leucemia Mieloide de Fase Crónica/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Adulto Joven
10.
Cancer Treat Res ; 161: 319-49, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24706230

RESUMEN

Infectious complications remain a significant issue in the care of patients with hematologic malignancies. Inherent immune defects related to the primary disease process are present in patients with disorders such as chronic lymphocytic leukemia, multiple myeloma, hairy cell leukemia, and Hodgkin lymphoma. Therapy-related immunosuppression is also commonplace in these patients. This includes not only treatment-related neutropenia, but also defects in cell-mediated immunity, such as those that occur with purine analog therapy. In this chapter, we will review the pathogenesis of infection in these disorders, as well as the spectrum of infectious complications seen and suggested strategies for the prevention of infection.


Asunto(s)
Antiinfecciosos/uso terapéutico , Infecciones/etiología , Leucemia/complicaciones , Linfoma/complicaciones , Humanos , Infecciones/diagnóstico , Infecciones/tratamiento farmacológico , Leucemia/microbiología , Leucemia/terapia , Linfoma/microbiología , Linfoma/terapia , Factores de Riesgo
11.
J Infect Dis ; 208(4): 559-63, 2013 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-23633406

RESUMEN

BACKGROUND: After completion of the Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Studies Program Number 403), SPS participants who had initially received placebo were offered investigational zoster vaccine without charge. This provided an opportunity to determine the relative safety of zoster vaccine in older adults following documented herpes zoster (HZ). METHODS: A total of 13 681 SPS placebo recipients who elected to receive zoster vaccine were followed for serious adverse events (SAE) for 28 days after vaccination. In contrast to the SPS, a prior episode of HZ was not a contraindication to receiving zoster vaccine. The SPS placebo recipients who received zoster vaccine included 420 who had developed documented HZ during the SPS. RESULTS: The mean interval between the onset of HZ and the receipt of zoster vaccine in the 420 recipients with prior HZ was 3.61 years (median interval, 3.77 years [range, 3-85 months]); the interval was <5 years for approximately 80% of recipients. The proportion of vaccinated SPS placebo recipients with prior HZ who developed ≥ 1 SAE (0.95%) was not significantly different from that of vaccinated SPS placebo recipients with no prior history of HZ (0.66%), and the distribution of SAEs in the 2 groups was comparable. CONCLUSIONS: These results demonstrate that the general safety of zoster vaccine in older persons is not altered by a recent history of documented HZ, supporting the safety aspect of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommendation to administer zoster vaccine to all persons ≥ 60 years of age with no contraindications, regardless of a prior history of HZ.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Vacuna contra el Herpes Zóster/administración & dosificación , Vacuna contra el Herpes Zóster/efectos adversos , Herpes Zóster/inmunología , Anciano , Anciano de 80 o más Años , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad
12.
Blood ; 117(6): 1911-6, 2011 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-21131588

RESUMEN

Prior genome-wide association (GWA) studies have identified 10 susceptibility loci for risk of chronic lymphocytic leukemia (CLL). To identify additional loci, we performed a GWA study in 407 CLL cases (of which 102 had a family history of CLL) and 296 controls. Moreover, given the strong familial risk of CLL, we further subset our GWA analysis to the CLL cases with a family history of CLL to identify loci specific to these familial CLL cases. Our top hits from these analyses were evaluated in an additional sample of 252 familial CLL cases and 965 controls. Using all available data, we identified and confirmed an independent association of 4 single-nucleotide polymorphisms (SNPs) that met genome-wide statistical significance within the IRF8 (interferon regulatory factor 8) gene (combined P values ≤ 3.37 × 10(-8)), located in the previously identified 16q24.1 locus. Subsetting to familial CLL cases, we identified and confirmed a new locus on chromosome 6p21.3 (combined P value = 6.92 × 10(-9)). This novel region harbors the HLA-DQA1 and HLA-DRB5 genes. Finally, we evaluated the 10 previously reported SNPs in the overall sample and replicated 8 of them. Our findings support the hypothesis that familial CLL cases have additional genetic variants not seen in sporadic CLL. Additional loci among familial CLL cases may be identified through larger studies.


Asunto(s)
Cromosomas Humanos Par 6/genética , Factores Reguladores del Interferón/genética , Leucemia Linfocítica Crónica de Células B/genética , Polimorfismo de Nucleótido Simple , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Antígenos HLA-DQ/genética , Cadenas alfa de HLA-DQ , Antígenos HLA-DR/genética , Cadenas HLA-DRB5 , Humanos , Leucemia Linfocítica Crónica de Células B/inmunología , Masculino , Oportunidad Relativa , Factores de Riesgo
13.
J Geriatr Oncol ; 13(5): 572-581, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35216939

RESUMEN

Non-Hodgkin lymphoma (NHL) is a disease of older adults, with a median age at diagnosis of 67 years. Treatment in older adults with NHL is challenging. The aging process is associated with a decline in functional reserve that varies among individuals, and results in an increasing risk of treatment-related toxicity and mortality. Chronological age and performance status fail to capture the multidimensional and heterogeneous nature of the aging process. A geriatric assessment (GA) screens multiple geriatric domains and provides a more accurate assessment of functional reserve. Several abbreviated GA tools have been developed for use in oncology clinics and help identify patients at high risk for chemotherapy-related toxicity and mortality. In this review, we explore GA tools validated for use in patients with NHL. We discuss the evidence behind GA-guided treatment in NHL and present a suggested approach to assessing frailty in this patient population.


Asunto(s)
Fragilidad , Linfoma no Hodgkin , Neoplasias , Anciano , Fragilidad/diagnóstico , Evaluación Geriátrica/métodos , Humanos , Linfoma no Hodgkin/tratamiento farmacológico , Neoplasias/terapia
14.
JCO Oncol Pract ; 18(11): e1807-e1817, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36126244

RESUMEN

PURPOSE: Treatment goals for patients with metastatic cancer include prolongation and maintenance of quality of life. Patients and oncologists have questioned the current paradigm of initial dose selection for systemic therapy; however, data on oncologists' dose selection strategies and beliefs are lacking. METHODS: We conducted an electronic international survey of medical oncologists who treat patients with breast and/or gastrointestinal cancers. Survey questions addressed experiences with, and attitudes toward, dose reduction at initiation (DRI) of a new systemic therapy for patients with metastatic cancer. RESULTS: Among 3,099 eligible oncologists, 367 responded (response rate 12%). Most (52%) reported using DRI at least 10% of the time to minimize toxicities. Gastrointestinal specialists were more likely to report DRI ≥ 10% of the time (72% v 50% of generalists and 51% of breast specialists, P < .005). Of those who dose reduced ≥ 10% of the time, 89% reported discussing potential tradeoffs between efficacy and toxicity with patients. Overall, 65% agreed it is acceptable to lower starting doses to reduce side effects even if it compromises efficacy; younger clinicians were more likely to agree (P < .005). There was strong support (89%) for future trials to determine optimal effective, rather than maximum tolerated, dose. CONCLUSION: Oncology practice varies with regard to discussion and individualized selection of starting doses in the metastatic setting. This study demonstrates a need for consideration of shared decision making regarding initial dose selection and strong support among oncologists for clinical studies to define optimal dosing and best practices for individualizing care.


Asunto(s)
Neoplasias , Oncólogos , Humanos , Calidad de Vida , Oncología Médica , Neoplasias/tratamiento farmacológico , Encuestas y Cuestionarios
15.
Emerg Infect Dis ; 17(10): 1855-64, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22000355

RESUMEN

Recent reports describe increasing incidence of non-Aspergillus mold infections in hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients. To investigate the epidemiology of infections with Mucorales, Fusarium spp., and Scedosporium spp. molds, we analyzed data from the Transplant-Associated Infection Surveillance Network, 23 transplant centers that conducted prospective surveillance for invasive fungal infections during 2001-2006. We identified 169 infections (105 Mucorales, 37 Fusarium spp., and 27 Scedosporium spp.) in 169 patients; 124 (73.4%) were in HCT recipients, and 45 (26.6%) were in SOT recipients. The crude 90-day mortality rate was 56.6%. The 12-month mucormycosis cumulative incidence was 0.29% for HCT and 0.07% for SOT. Mucormycosis incidence among HCT recipients varied widely, from 0.08% to 0.69%, with higher incidence in cohorts receiving transplants during 2003 and 2004. Non-Aspergillus mold infections continue to be associated with high mortality rates. The incidence of mucormycosis in HCT recipients increased substantially during the surveillance period.


Asunto(s)
Micosis/epidemiología , Infecciones Oportunistas/epidemiología , Trasplante , Adulto , Antifúngicos/uso terapéutico , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Micosis/tratamiento farmacológico , Micosis/microbiología , Infecciones Oportunistas/tratamiento farmacológico , Infecciones Oportunistas/microbiología , Trasplante/efectos adversos , Estados Unidos/epidemiología
16.
Ann Intern Med ; 152(9): 545-54, 2010 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-20439572

RESUMEN

BACKGROUND: The herpes zoster vaccine is effective in preventing herpes zoster and postherpetic neuralgia in immunocompetent older adults. However, its safety has not been described in depth. OBJECTIVE: To describe local adverse effects and short- and long-term safety profiles of herpes zoster vaccine in immunocompetent older adults. DESIGN: Randomized, placebo-controlled trial with enrollment from November 1998 to September 2001 and follow-up through April 2004 (mean, 3.4 years). A Veterans Affairs Coordinating Center generated the permutated block randomization scheme, which was stratified by site and age. Participants and follow-up study personnel were blinded to treatment assignments. (ClinicalTrials.gov registration number: NCT00007501) SETTING: 22 U.S. academic centers. PARTICIPANTS: 38 546 immunocompetent adults 60 years or older, including 6616 who participated in an adverse events substudy. INTERVENTION: Single dose of herpes zoster vaccine or placebo. MEASUREMENTS: Serious adverse events and rashes in all participants and inoculation-site events in substudy participants during the first 42 days after inoculation. Thereafter, vaccination-related serious adverse events and deaths were monitored in all participants, and hospitalizations were monitored in substudy participants. RESULTS: After inoculation, 255 (1.4%) vaccine recipients and 254 (1.4%) placebo recipients reported serious adverse events. Local inoculation-site side effects were reported by 1604 (48%) vaccine recipients and 539 (16%) placebo recipients in the substudy. A total of 977 (56.6%) of the vaccine recipients reporting local side effects were aged 60 to 69 years, and 627 (39.2%) were older than 70 years. After inoculation, herpes zoster occurred in 7 vaccine recipients versus 24 placebo recipients. Long-term follow-up (mean, 3.39 years) showed that rates of hospitalization or death did not differ between vaccine and placebo recipients. LIMITATIONS: Participants in the substudy were not randomly selected. Confirmation of reported serious adverse events with medical record data was not always obtained. CONCLUSION: Herpes zoster vaccine is well tolerated in older, immunocompetent adults. PRIMARY FUNDING SOURCE: Cooperative Studies Program, Department of Veterans Affairs, Office of Research and Development; grants from Merck to the Veterans Affairs Cooperative Studies Program; and the James R. and Jesse V. Scott Fund for Shingles Research.


Asunto(s)
Vacuna contra el Herpes Zóster/efectos adversos , Herpes Zóster/prevención & control , Neuralgia Posherpética/prevención & control , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Humanos , Inmunocompetencia , Persona de Mediana Edad , Factores de Riesgo
17.
J Geriatr Oncol ; 12(2): 320-325, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32972884

RESUMEN

A major evolution in the treatment of patients with diffuse large B-cell lymphoma (DLBCL) occurred almost two decades ago, with clinical trials demonstrating that the addition of rituximab (R) to cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), which had been the "gold standard" of therapy since 1976, significantly improved outcome, including response rate and disease-free survival, of these patients. Since the adoption of R-CHOP, subsequent clinical trials have attempted to improve upon outcomes achieved with R-CHOP, with a variety of approaches examined. These have included dose intensification, which may be applicable in younger patients, but not in the many older or frailer patients with a disease with median age at diagnosis in the 60's. Newer anti-CD20 monoclonal antibodies have been substituted for rituximab in frontline regimens. A series of new agents, with unique mechanisms of action, have been added to the R-CHOP backbone. Rituximab-based, non-anthracycline regimens have been studied for older, more frail patients. The utility of maintenance therapy in responding patients has been re-examined, despite the lack of benefit found in the US Intergroup trial. Advances in molecular and genetic aspects of DLBCL have emerged since the seminal R-CHOP trials, demonstrating the DLBCL is not a single entity, but instead a spectrum of multiple disease subtypes. Attempts have been made to identify those patients at baseline who have poorer outcomes with standard approaches, utilizing laboratory and imaging findings. Moving forward, different risk-adapted treatment approaches will be studied to in an effort to improve overall outcome beyond R-CHOP.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células B Grandes Difuso , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Prednisona/uso terapéutico , Rituximab/uso terapéutico , Resultado del Tratamiento , Vincristina/uso terapéutico
18.
Cancer Treat Res Commun ; 29: 100466, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34655862

RESUMEN

Evidence-based US guidelines provide recommendations for the use of granulocyte colony-stimulating factor (G-CSF) as supportive therapy in patients with cancer receiving chemotherapy. Pegfilgrastim is recommended for FN prophylaxis in patients with non-myeloid malignancies receiving a high-risk chemotherapy regimen, or an intermediate-risk regimen if one or more risk factors are present. The guidelines highlight the patient characteristics and chemotherapy regimens for solid tumors and hematologic malignancies that may influence a patient's overall risk of FN and may benefit from pegfilgrastim support. This review aimed to evaluate how pegfilgrastim use in patients with cancer receiving myelosuppressive chemotherapy in routine clinical practice aligns with evidence-based US guidelines. Examination of the literature revealed widespread deviation in relation to under- and over-prescribing, and timing of administration in US clinical practice. Pegfilgrastim is often over-prescribed in patients receiving palliative chemotherapy and those at low risk of FN. Potential under-prescribing of pegfilgrastim was also observed. In this literature search, data that appear to support same-day administration of pegfilgrastim were from uncontrolled studies that were limited in size. Analyses of healthcare claims data clearly favored next-day use, with statistically significant increases in FN incidence among patients receiving same-day pegfilgrastim versus those treated 1-4 days post-chemotherapy. Earlier-than-recommended administration typically occurs at the physician's discretion where next-day administration might present barriers to the patient receiving supportive therapy.There is a need to ensure appropriate prescribing to optimize patient outcomes, as deviation from the guideline recommendations was associated with increased incidence of FN and hospitalization.


Asunto(s)
Filgrastim/uso terapéutico , Adhesión a Directriz/normas , Neutropenia/inducido químicamente , Neutropenia/tratamiento farmacológico , Polietilenglicoles/uso terapéutico , Filgrastim/farmacología , Humanos , Cumplimiento de la Medicación , Polietilenglicoles/farmacología , Estados Unidos
19.
J Geriatr Oncol ; 12(6): 894-901, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33423932

RESUMEN

INTRODUCTION: Although treatment approaches to younger fit patients with mantle cell lymphoma (MCL) are well-described, the optimal treatment of older or less fit patients with varying comorbidities is less clear. The objectives of this study were to examine first-line treatment patterns, and the impact of comorbidities and age on treatment choices and overall survival (OS) in a large, predominantly older, Medicare population. PATIENTS AND METHODS: In Medicare data from 1/1/2007-8/31/2015, 3,008 patients with MCL were identified. Data on age, gender, race, Charlson comorbidities, Charlson comorbidity index (CCI), timing of injectable MCL therapies, and OS were collected and analyzed. RESULTS: Median age of the study population was 75.5 (range, 33-107; 25th, 75th: 69.9, 81.5) years. Over half of the individuals had ≥two comorbidities. The CCI was 1-2 in 45%, and 3-4 in 26.6% of patients. Rituximab was the most commonly used agent, regardless of age or comorbidity, in the first 60 days following diagnosis, being administered to 40.2% of patients. In contrast, administration of cyclophosphamide, doxorubicin, vincristine, or bendamustine in the first 60 days after diagnosis was less common (17.9%, 13.1%, 17.2%, and 12%, respectively). Overall survival was 3.23 (range, 0.003-7.668) years, and decreased with increasing number of comorbidities. DISCUSSION: Our analysis of a real-world patient population with MCL found that older patients have a high rate of comorbidities which impact administered treatment and subsequent OS. Our findings can be used to prospectively guide treatment decisions in these older, frailer, non-transplant-eligible patients, considering the impact of age and comorbidities on such choices.


Asunto(s)
Linfoma de Células del Manto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Humanos , Linfoma de Células del Manto/tratamiento farmacológico , Medicare , Prednisona/uso terapéutico , Rituximab/uso terapéutico , Estados Unidos/epidemiología , Vincristina/uso terapéutico
20.
J Clin Oncol ; 39(18): 2037-2048, 2021 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-33939491

RESUMEN

PURPOSE: To provide recommendations for appropriate dosing of systemic antineoplastic agents in obese adults with cancer. METHODS: A systematic review of the literature collected evidence regarding dosing of chemotherapy, immunotherapy, and targeted therapies in obese adults with cancer. PubMed and the Cochrane Library were searched for randomized controlled trials, meta-analyses, or cohort studies published from November 1, 2010, through March 27, 2020. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS: Sixty studies, primarily retrospective, were included in the review. Overall, the evidence supported previous findings that obese adult patients tolerate full, body-size-based dosing of chemotherapy as well as nonobese patients. Fewer studies have addressed the dosing of targeted therapies and immunotherapies in relation to safety and efficacy in obese patients. RECOMMENDATIONS: The Panel continues to recommend that full, weight-based cytotoxic chemotherapy doses be used to treat obese adults with cancer. New to this version of the guideline, the Panel also recommends that full, approved doses of immunotherapy and targeted therapies be offered to obese adults with cancer. In the event of toxicity, the consensus of the Panel is that dose modifications of systemic antineoplastic therapies should be handled similarly for obese and nonobese patients. Important areas for future research include the impact of sarcopenia and other measures of body composition on optimal antineoplastic dosing, and more customized dosing based on pharmacokinetic or pharmacogenetic factors.Additional information is available at www.asco.org/supportive-care-guidelines.


Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Obesidad/complicaciones , Antineoplásicos/efectos adversos , Humanos , Revisiones Sistemáticas como Asunto
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