RESUMEN
Neutrophils are an integral component of the innate immune system and key regulators of cell-mediated defense against bacterial and fungal pathogens. The potential of granulocyte transfusions has been investigated to temporarily replenish innate immune function to prevent and/or treat infections in patients with severe neutropenia or neutrophil dysfunction. However, evidence has been largely theoretical, experimental, and/or inconclusive. Clinical efficacy has yet to be confirmed by large-scale randomized controlled clinical trials. Performing such trials has been hampered by low granulocyte collection yield and poor patient accrual. We provide a practical summary of the current literature surrounding the practice of granulocyte transfusion.
Asunto(s)
Transfusión de Leucocitos , Neutropenia , Granulocitos , HumanosRESUMEN
BACKGROUND/AIM: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy where antioxidant enzyme peroxiredoxin 6 (Prx6) has previously been associated with adverse outcomes. Its systemic effects in DLBCL are unknown. MATERIALS AND METHODS: This study included 53 patients with DLBCL, five patients with primary central nervous system lymphoma (PCNSL) and 20 healthy controls. The expression of Prx6 was evaluated immunohistochemically in DLBCL tissue samples and compared to its expression in blood serum. RESULTS: Prx6 expression was the highest in healthy controls, followed by DLBCL patients and PCNSL patients. Febrile neutropenic infection after the first treatment course was associated with low pre-treatment Prx6 serum levels (<14 ng/ml) (p=0.025, OR=8.615, 95% confidence interval=1.032-71.933). Serum levels of Prx6 recovered after treatment (p=0.006). CONCLUSION: Patients with low Prx6 levels might be more prone to treatment-related adverse effects through elevated levels of oxidative stress.
Asunto(s)
Infecciones/etiología , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/complicaciones , Neutropenia/complicaciones , Neutropenia/etiología , Peroxiredoxina VI/sangre , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores , Femenino , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Medición de Riesgo , Factores de RiesgoRESUMEN
Animal models facilitate evaluation of vaccine efficacy at relatively low cost. This study was a comparative evaluation of the immunogenicity and protective efficacy of a new 13-valent pneumococcal conjugate vaccine (PCV13) with a control vaccine in a mouse model. After vaccination, anti-capsular antibody levels were evaluated by pneumococcal polysaccharide (PnP) enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic killing assay (OPA). Also, mice were challenged intraperitoneally with 100-fold of the 50% lethal dose of Streptococcus pneumoniae. The anti-capsular IgG levels against serotypes 1, 4, 7F, 14, 18C, 19A, and 19F were high (quartile 2 >1,600), while those against the other serotypes were low (Q2 ≤ 800). Also, the OPA titres were similar to those determined by PnP ELISA. Comparative analysis between new PCV13 and control vaccination group in a mouse model exhibited significant differences in serological immunity of a few serotypes and the range of anti-capsular IgG in the population. Challenge of wild-type or neutropenic mice with serotypes 3, 5, 6A, 6B, and 9V showed protective immunity despite of induced relatively low levels of anti-capsular antibodies. With comparison analysis, a mouse model should be adequate for evaluating serological efficacy and difference in the population level as preclinical trial.
Asunto(s)
Inmunogenicidad Vacunal , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/inmunología , Animales , Anticuerpos Antibacterianos , Cápsulas Bacterianas/inmunología , Modelos Animales de Enfermedad , Inmunoglobulina G/sangre , Ratones , Neutropenia , Proteínas Opsoninas , Fagocitosis , Infecciones Neumocócicas/microbiología , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/efectos adversos , Polisacáridos Bacterianos/inmunología , Serogrupo , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/efectos adversos , Vacunas Conjugadas/inmunologíaRESUMEN
BACKGROUND: Few studies have been performed to identify factors that are associated with an increased risk of infections during the neutropenic period in patients undergoing allogeneic stem cell transplantation (allo-SCT). The aim of this study was to identify the host immune cells responsible for infections before engraftment. METHODS: A total of 282 patients who underwent allo-SCT were enrolled. Peripheral blood samples were collected before conditioning therapy. Expression of CD161-expressing T cells, natural killer cells, and immature myeloid cells was analyzed by flow cytometry. Microbially and clinically defined infections and fevers of unknown origin as proposed by the Immunocompromised Host Society were included in this study. RESULTS: The median age was 45 years (range, 16-68 years). Patients had various hematologic disorders and were transplanted from human leukocyte antigen (HLA)-matched siblings, unrelated donors, and familial HLA-mismatched donors. In univariate analysis, younger age and a familial HLA-mismatched donor were risk factors for the occurrence of infections. After adjusting for potential variables in univariate analysis, multivariate analyses revealed that a lower frequency of CD3+ CD4+ CD161+ cells was significantly associated with the occurrence of neutropenic infections. An age of 35 years or younger and allografting from familial HLA-mismatched donors showed a trend toward higher infection rates. CONCLUSION: Our data indicated that a lower frequency of CD3+ CD4+ CD161+ T cells in peripheral blood before conditioning therapy was associated with a higher incidence of infection during the neutropenic period. These results suggest that recipient innate T cells with expression of C-type lectin CD161 can guard against infections before engraftment.
Asunto(s)
Fiebre de Origen Desconocido/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Inmunidad Celular , Huésped Inmunocomprometido/inmunología , Neutropenia/inmunología , Linfocitos T/inmunología , Acondicionamiento Pretrasplante/efectos adversos , Adolescente , Adulto , Anciano , Complejo CD3/metabolismo , Linfocitos T CD4-Positivos/inmunología , Femenino , Fiebre de Origen Desconocido/sangre , Fiebre de Origen Desconocido/epidemiología , Citometría de Flujo , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Células Asesinas Naturales/metabolismo , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/efectos adversos , Agonistas Mieloablativos/uso terapéutico , Células Mieloides/metabolismo , Subfamilia B de Receptores Similares a Lectina de Células NK/metabolismo , Neutropenia/sangre , Neutropenia/epidemiología , Linfocitos T/metabolismo , Trasplante Homólogo/efectos adversos , Adulto JovenRESUMEN
The patient granulocyte-colony stimulating factor (G-CSF) response is represented by the leukocyte peak in the blood induced by a single dose of G-CSF after chemotherapy, and is correlated with subsequent neutropenic infection risk. General patterns for a meaningful risk group stratification, have not yet been determined. Two independent data sets including a total of 306 cases with myeloma or lymphoma and autologous blood stem cell transplant were available. An infection susceptibility curve plotted according to ranked G-CSF responses from a multicenter study reproduced and validated a curve from the previous single center. Two trend changes were seen within these curves at around 11,000 and 22,000 leukocytes/µL, which separated three groups with a high, medium and low risk of infection. While G-CSF response is related to the consecutive duration of neutropenia, it retains additional independent predictive information for infection risk (p<0.0001) and, more important, is a tool available before the onset of the critical period.