Eficacia y seguridad de posaconazol como profilaxis antifúngica en pacientes neutropénicos severos por quimioterapia de inducción o trasplante alogénico de médula ósea con neoplasia hematológica con alto riesgo de infección fúngica invasiva / Efficacy and safety of posaconazole as antifungal prophylaxis in severe neutropenic patients by induction chemotherapy or allogeneic bone marrow transplantation with haematological malignancy with high risk of invasive fungal infection

INTRODUCCIÓN: Antecedentes: El presente dictamen expone la evaluación de tecnología de la eficacia y seguridad de posaconazil como profilaxis antifúngica en pacientes neutropénicos severos por quimioterapia de inducción o trasplante alogénico de médula ósea, con neoplasia hematológica con alto riesgo de infección fúngica invasiva. Aspectos Generales: Las infecciones fúngicas invasiva (IFI) son infecciones de tipo oportunista, las cuales son una causa principal de morbilidad y mortalidad en pacientes en condiciones críticas o inmunocomprometidos como por ejemplo aquellos en estado neutropénico recibiendo tratamiento con quimioterapia por inducción debido a malignidades hematológicas. La frencuencia y diversidad de las IFIs depende de la enfermedad de fondo, la terapia de manejo y la incidencia de la enfermedad de fondo. La aspergillosis y candidiasis son las IFIs más comunes y causantes de aproximadamente el 40 y 50% de IFIs en pacientes con neutropenia. METODOLOGÍA: Estrategia de Búsqueda: Se llevó a cabo una búsqueda sistemática de la literatura con respecto a la eficacia y seguridad de posaconazol en pacientes neutropécnicos severos por quimioterapia de inducción o trasplante alogénico de médula ósea, con neoplasia hematológica con alto riesgo de infección fúngica invasiva. para la búsqueda primaria se revisó en primer lugar la información disponible por entidades reguladoras y normativas de autorización comercial como la Administración de Drogas y Alimentos (FDA) de Estaods Unidos, la Agencia de Medicamentos Europea (EMA) y la Dirección General de Medicamentos y Drogas (DIGEMID) en el Perú. RESULTADOS: Se realizó una búsqueda para así procurar recabar toda de evidencia disponible que pueda responder a la pregunta PICO de interés: eficacia y seguridad del uso de posaconazol como profilaxis antifúngica en pacientes neutropénicos severos por quimioterapia de inducción o trasplante alogénico de médula ósea, con neoplasia hematológica con alto riesgo de infección fúngica invasiva. Se encontró que la información fue abundante, por lo que se seleccionaron sólo los estudios de mejor calidad metodológica para la descripción y evaluación de la evidencia. CONCLUSIONES: El presente dictamen expone la evaluación de la eficacia y seguridad de posaconazol como profilaxis antifúngica en pacientes hematológicos neutropénicos y alto riesgo de infecciones fúngicas invasivas. Se ha encontrado evidencia que sustenta la eficacia y seguridad del posaconazol como profilaxis antifúngica en pacientes hematológicos neutropénicos y alto riesgo de infecciones fúngicas invasivas. El Instituto de Evaluación de Tecnologías en Salud e Investigación-IETSI aprueba el uso de posaconazol como profilaxis antifúngica en pacientes hematológicos neutropénicos con alto riesgo de infecciones fúngicas invasivas. El Dictamen Preliminar tendrá una vigencia de dos años a partir de la fecha de su publicación.

Estudo da variação neutropênica pelo sulfato de vincristina em cães com tvt tratados em um hospital veterinário do Noroeste Paulista / Neutropenic variation by vincristine sulfate in tvt dogs treated in a veterinary hospital in northwestern São Paulo / Estudio de la variación neutropénica por sulfato de vincristina en perros con tvt tratados en el hospital veterinario del Noroeste Paulista

O presente estudo avaliou dados epidemiológicos de neutropenia induzida por sulfato vincristina em cães com Tumor Venéreo Transmissível (TVT), num Hospital Veterinário do Noroeste paulista. Para tanto, trata-se de um estudo do tipo retrospectivo de protocolos eletrônicos e formulários manuais de dados digitalizados de 51 casos de TVT. O atendimento ambulatorial e de internação desses animais foi realizado no período de setembro de 2006 a dezembro de 2009. Dentre os resultados, destaca-se que 51 animais foram diagnosticados com TVT, sendo 37 fêmeas (73%) e 14 (27%) machos; 46 animais (90,2%) foram tratados exclusivamente com sulfato de vincristina. Os cães Sem Raça Definida-SRD (n=28) foram os maiores acometidos com 54,9%; seguidos pelos Poodles com quatro cães (7,84%). Os animais com idade entre 37 e 84 meses obtiveram a maior porcentagem de acometimento pelo TVT com 20 casos (39,22%). Em doze animais (23,52%) foi observada neutropenia (valores entre 390 a 1927 cél/µL). Conclusão: a possível toxicidade medular induzida pela vincristina foi verificada pela descrição da neutropenia. Dessa forma, a identificação de quadros neutropênicos, por meio da realização de hemogramas semanais, é considerada obrigatória e de extrema relevância devido à prevalência de mielotoxicidade secundária à utilização deste quimioterápico...

The present study aims to assess epidemiological data on neutropenia induced by vincristine sulfate among dogs with Canine Transmissible Venereal Tumor (CTVT) at a veterinary hospital in the Northwestern region in the São Paulo State. Methodology: This is a retrospective study of electronic protocols and digitalized data from manually filled form from 51 CTVT cases. These animals were treated in an outpatient care clinic and hospitalization took place from September 2006 to December 2009. Results: 51 animals were diagnosed with CTVT; among these, 37 were female (73%) and 14 were male (27%). From these, 46 animals (90.2%) were treated exclusively with vincristine sulfate. Among them, mongrels (n=28) were the most common, with 54.9%, followed by Poodles, with 4 dogs (7.84%). Animals aged from 37 and 84 months were the largest age group, with 20 cases (39.22 %). Neutropenia (390 to 1927 cells/µL) was observed in 12 animals. Conclusion: possible vincristine-induced marrow toxicity was verified by the description of neutropenia. Thus, neutropenia identification through weekly blood count cells is considered extremely important and mandatory due to the prevalence of myelotoxicity following treatment with this chemotherapeutic drug...

Este estudio busca evaluar datos epidemiológicos de neutropenia inducida por sulfato vincristina en perros con Tumor Venéreo Transmisible (TVT), en un Hospital Veterinario del Noroeste Paulista. Es un estudio del tipo retrospectivo de protocolos electrónicos y formularios manuales de datos digitalizados de 51 casos de TVT. El atendimiento de ambulatorio y de internación de esos animales se realizó en el período de septiembre de 2006 a diciembre de 2009. Entre los resultados, se destaca que 51 animales fueron diagnosticados con TVT, siendo 37 hembras (73%) y 14 (27%) machos; 46 animales (90,2%) fueron tratados exclusivamente con sulfato de vincristina. Los perros Sin Raza Definida – SRD (n=28) fueron los más acometidos con 54,9%; seguidos por los Poodles con cuatro perros (7,84%). Los animales con edad entre 37 y 84 meses obtuvieron mayor porcentaje de acometimiento por TVT, con 20 casos (39,22%). En doce animales (23,52%0 se ha observado neutropenia (valores entre 390 a 1927 cél/µL). Conclusión: la posible toxicidad medular inducida por vincristina se há verificado por la descripción de la neutropenia. Así, la identificación de cuadros neutropénicos por medio de realización de hemogramas semanales, es considerada obligatoria y de extrema relevancia debido a la prevalencia de mielotoxicidad secundaria a la utilización de este quimioterápico...

Recurrent neutropenia induced by rifabutin in a renal transplant recipient

No abstract available.

Discrimination of acute lymphoblastic leukemia from systemic-onset juvenile idiopathic arthritis at disease onset

OBJECTIVE: To assess clinical and laboratory features that differentiate acute lymphoblastic leukemia from systemic juvenile idiopathic arthritis at disease onset. METHODS: Fifty-seven leukemia patients with musculoskeletal involvement, without blasts on peripheral blood and without glucocorticoid therapy at disease onset and 102 systemic juvenile idiopathic arthritis patients (International League of Associations for Rheumatology criteria) were retrospectively evaluated. The following features were examined: fever, rheumatoid rash, arthritis, limb pain, hepatomegaly, splenomegaly, pericarditis, myocarditis, pleuritis, weight loss, bleeding, anemia, leukopenia, neutropenia, thrombocytopenia, erythrocyte sedimentation rate, and lactic dehydrogenase levels. RESULTS: The median age at disease onset was significantly higher in leukemia patients than in those with systemic-onset juvenile idiopathic arthritis (5.8 vs. 3.8 years). In addition, the frequencies of limb pain, hepatomegaly, weight loss and hemorrhagic manifestations were significantly higher in leukemia patients than in systemic-onset juvenile idiopathic arthritis patients (70 percent vs. 1 percent, 54 percent vs. 32 percent, 30 percent vs. 8 percent, and 9 percent vs. 0 percent, respectively). Likewise, the frequencies of anemia, leukopenia, neutropenia, thrombocytopenia and high lactic dehydrogenase levels were statistically higher in leukemia patients than in patients with systemic-onset juvenile idiopathic arthritis (88 percent vs. 57 percent, 39 percent vs. 1 percent, 60 percent vs. 1 percent, 77 percent vs. 1 percent, and 56 percent vs. 14 percent, respectively). Remarkably, multivariate analysis revealed that limb pain (OR = 553; 95 percent CI =46.48-6580.42) and thrombocytopenia (OR = 754.13; 95 percent CI =64.57-8806.72) were significant independent variables that differentiated leukemia from systemic-onset juvenile idiopathic arthritis. The R2 of the Nagelkerke test was 0.91, and the Kaplan-Meier survival curves were similar for acute lymphoblastic leukemia patients with and without limb pain. CONCLUSION: Our study emphasizes the importance of investigating leukemia in patients presenting with musculoskeletal manifestations and, in particular, limb pain associated with thrombocytopenia.

Plasma levels of procalcitonin and eight additional inflammatory molecules in febrile neutropenic patients

OBJECTIVE: This study aimed to examine the association between different inflammatory markers and specific clinical endpoints in patients with febrile neutropenia. METHOD: We prospectively evaluated the expression of procalcitonin (PCT), interleukin 8 (IL-8), induced protein-10, tumor necrosis factor alpha (TNF-a), two soluble TNF-a receptors (sTNF-R I and sTNF-R II), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 alpha, and eotaxin in 37 episodes of febrile neutropenia occurring in 31 hospitalized adult onco-hematologic patients. Peripheral blood samples were collected in the morning at inclusion (day of fever onset) and on days 1, 3, and 7 after the onset of fever. Approximately 2-3 ml of plasma was obtained from each blood sample and stored at -80°C. RESULTS: The sTNF-R II level at inclusion (day 1), the PCT level on the day of fever onset, and the change (day 3 - day 1) in the IL-8 and eotaxin levels were significantly higher in patients who died during the 28-day follow-up. A requirement for early adjustment of antimicrobial treatment was associated with higher day 3 levels of IL-8, sTNF-R II, PCT, and MCP-1. CONCLUSION: Procalcitonin, sTNF-R II, IL-8, MCP-1, and eotaxin could potentially be used to assess the risk of death and the requirement for early adjustment of antimicrobial treatment in febrile, neutropenic onco-hematologic patients. The levels of the other markers showed no association with any of the evaluated endpoints.

Role of fluconazole prophylaxis in decreasing Candida infection and colonization among severely neutropenic children with hematological malignancies

To Assess the role of antifungal prophylaxis in decreasing Candida infection and colonization in severely neutropenic children with hematological malignancies. Sixty four patients with severe neutropenia are randomized equally into 2 groups on 1:1 basis either to receive fluconazole prophylaxis [study group], or to receive placebo [control group]. Fluconazole antifungal prophylaxis/ placebo It was continued for 6 weeks, and follow up of the patient done until either Prophylaxis success by recovery from severe neutropenia [ANC

Novel ELANE Gene Mutation in a Korean Girl with Severe Congenital Neutropenia

Severe congenital neutropenia is a heterozygous group of bone marrow failure syndromes that cause lifelong infections. Mutation of the ELANE gene encoding human neutrophil elastase is the most common genetic alteration. A Korean female pediatric patient was admitted because of recurrent cervical lymphadenitis without abscess formation. She had a past history of omphalitis and isolated neutropenia at birth. The peripheral blood showed a markedly decreased absolute neutrophil count, and the bone marrow findings revealed maturation arrest of myeloid precursors at the promyelocyte to myelocyte stage. Her direct DNA sequencing analysis demonstrated an ELANE gene mutation (c.607G > C; p.Gly203Arg), but her parents were negative for it. She showed only transient response after subcutaneous 15 microg/kg/day of granulocyte colony stimulating factor administration for six consecutive days. During the follow-up observation period, she suffered from subsequent seven febrile illnesses including urinary tract infection, septicemia, and cellulitis.

Significance of C-reactive protein during febrile neutropenia in pediatric malignancies.

Fifty episodes of febrile neutropenia (FN) in 33 children with malignancies were studied to evaluate the usefulness of C-reactive protein (CRP) levels as an indicator of infection, and the efficacy of antibiotic therapy. Nineteen FN episodes occurred in children with documented infection whereas, 9 and 22 episodes occurred with probable infection and fever of unknown origin, respectively. CRP positivity during episodes of documented and probable infection was significantly higher than with febrile episodes of unknown origin. Blood culture was positive in 15 episodes; of these, CRP was positive in 11. CRP declined to normal on 7th day of antibiotic therapy. CRP is a useful indicator of infection in neutropenic children and also in determining the efficacy of antibiotic therapy.

Serum complement 3 (C3) and complement 4 (C4) level in febrile neutropenia patients at Dr. Kariadi Hospital, Semarang and Dr. Moewardi Hospital, Surakarta.

AIM: to identify the serum complement 3 (C3) and complement 4 (C4) level in febrile neutropenia and non-febrile neutropenia patients. METHODS: this is a cross-sectional prospective study. Samples were collected from patients with febrile neutropenia as sample group and patients with neutropenia but without fever as control. Both groups were tested for serum complement 3 and complement 4 level, and the data were analyzed using student T-test. RESULTS: from 37 neutropenia patients, 23 were classified as febrile neutropenia group and 14 in non-febrile neutropenia as control group. Total mean neutrophil count was 653.22/ml serum in sample group and 594.36/ml serum in control group (p=0.575). Mean C3 level was 95.74 ug/dl in sample group and 130.00 ug/dl in control group, showing significant difference with p=0.031. The mean serum C4 level was 34.13 ug/ml in sample group and 34.00 ug/dl in control group, the difference is not significant with p=0.98. When sample C3 and C4 data were combined, the total level was 125.61 ug/ml, which was significantly lower than the total C3 and C4 in control group 184.07 ug/dl. (p=0.04). CONCLUSION: in febrile neutropenia there is significant decrease of serum C3 level compared to non-febrile neutropenia. Serum C4 level in febrile neutropenia group is lower than the non-febrile neutropenia group, but the difference is not significant.

Proteína C reactiva y procalcitonina como marcadores de infección bacteriana en niños con neutropenia febril posterior a trasplante alogénico de progenitores hematopoyéticos / C reactive protein and procalcitonin levels for the diagnosis of invasive bacterial infections in allogenic hematopoietic stem cell transplantation recipients

Background: The main causes of complications of allogenic hematopoietic stem cell transplantation are infections and graft versus host disease. Aim: To assess the predictive value of C reactive protein (CRP) and procalcitonin (PCT) in the diagnosis of invasive bacterial infections in children with febrüe neutropenia after an allogenic hematopoietic stem cell transplantation. Material and methods: Prospective follow up of patients aged 18 years or íess, with febrile neutropenia after an allogenic hematopoietic stem cell transplantation. In all patients, cultures from sterile sites, CRP and PCT determinations were done. CRP levels were also measured prior to transplantation and three times per week for 30 days after the procedure. An independent evaluator, blinded to the results of CRP and PCT, classified children as with or without invasive bacterial infection. Results: Thirty three patients aged 9±5 years (21 males) were studied. Eight had an invasive bacterial infection. Sensitivity, specificity, positive and negative predictive values of a CRP ³90 mg/L for the diagnosis of invasive bacterial infection were 25, 80, 29 and 77 percent, respectively. The figures for a PCT ³0.7 ng/ml were 43, 78, 38 and 82 percent, respectively. No differences in repeated CRP values measured during evolution, were observed. Conclusions: A CRP ³90 mg/L or a PCT ³0.7 ng/ml had a high specificity and negative predictive value but low sensitivity for the diagnosis of invasive bacterial infections in recipients of allogenic hematopoietic stem cell transplantation.

Neutropenia inmune - aloinmune neonatal IgG serica reactiva y fenotipo especifico de los neutrofilos evaluados por citometria de flujo / Autoimmune-alloimmune neonatal neutropenia. Serum reactive IgG and neutrophil-specific

La neutropenia inmune se diagnostica por la presencia de auto o aloanticuerpos reactivos con losneutrófilos. La neutropenia aloinmune neonatal es consecuencia de la sensibilización materna alos antígenos específicos de los neutrófilos paternos que afectan al neonato al atravesar la barrera placentaria. Se presentan 4 casos de niños, 2 de ellos hermanos consanguíneos con doble vínculo. Se estudiaron los sueros de los pacientes y sus padres. Por citometría de flujo se establecen los valores de referencia de la IgG sérica reactiva con los neutrófilos en voluntarios sanos, para 3 diluciones (1/2, 1/5 y 1/20) en reacción autóloga(suero y células de un mismo individuo) y heteróloga (suero y células de diferentes individuos). Los resultadosse expresan por un índice definido como el cociente entre la mediana de la intensidad de fluorescencia media del suero incógnita y la de un suero utilizado como referencia. Por leucoaglutinación se evaluó la dilucióndel suero 1/20. Se determinó el nivel de complejos inmunes circulantes. Se determinó el fenotipo, para los epitopes HNA-1a, HNA-1b y HNA-2a. En los 4 niños se encontró IgG reactiva y/o factores aglutinantes; 2/3 sueros maternos fueron reactivos con los neutrófilos del cónyuge y de los hijos. Los complejos inmunes circulantes fueron positivos en 2/4 sueros negativos en 3/3 sueros maternos. Se encontró incompatibilidad materno-infantil en los 4 casos. Las 3 madres tenían igual fenotipo: homocigotos NA1/NA1, NB1+. En síntesis, se presenta el hallazgo de 4 casos con neutropenia inmune: 3/4 auto-inmune, 1/3 se asocia a complejos inmunes circulantes y 1/4 con neutropenia neonatal aloinmune

Auto or alloantibodies reactive with neutrophils define immune neutropenia. Alloimmune neonatal neutropenia is caused by maternal sensitization to paternal neutrophil antigens, resulting in IgG antibodies that are transferred to the fetus through the placenta. We present the studies in 4 children from 3 families with neutropenia of unknown origin (two of them were brothers). Theywere evaluated by flow cytometry in parallel with leukoagglutination. Reference values were established forserum reactive IgG in healthy volunteers for three dilutions (1/2, 1/5 and 1/20), both for the autologous reaction (serum and cells of the same individual) and for the heterologous reaction (serum and cells of differentindividuals). Results were expressed by an index defined by the quotient of the mean fluorescence intensityof the patient’s serum divided by that of the reference serum. Serum reactive/agglutinant factors and circulating immune complexes were evaluated in patients and parents serum. Neutrophil specific phenotypes weredetermined for HNA-1a, HNA-1b and HNA-2a. Reactive IgG/agglutinant factors were found in 4 children. Twomaternal sera were reactive against paternal and/or children neutrophils. Circulating immune complexes weredetected in 2/4 children sera and were negative in 3/3 maternal sera. Maternal/children incompatibility wasdetected in the four cases. The three mothers had the same phenotype: homozygous NA1/NA1, NB1+

Granulocyte Antibodies in Korean Neonates with Neutropenia

Neonatal alloimmune neutropenia (NAN) is a disease that can cause severe and prolonged neutropenia in neonates. However, no report is available on the incidence of granulocyte antibody in neonates, the target antigen of this antibody, and the estimated incidence of NAN in Korea. Among a total of 856 neonates admitted to a neonatal intensive care unit (NICU) over a five year period, a total of 105 neonates with neutropenia were enrolled in this study. Positive reactions were observed in the sera of six neonates (5.7%, 6/105) by mixed passive hemagglutination assay (MPHA). To confirm the presence of NAN, MPHA and granulocyte antigen typing (HNA-1a, -1b, -2a, -4a, and -5a) were performed on neonatal and maternal blood. To differentiate granulocyte antibody and HLA antibody, MPHA was also performed using HLA antibody adsorbed serum. We confirmed three cases (2.9%, 3/105) of NAN among neonates with neutropenia in which granulocyte antibody specificities (two anti-HNA-1b and one anti-HNA-1a) and fetomaternal granulocyte antigen mismatches were identified. In this study, the estimated incidence of NAN was 0.35% (3/856) among neonates admitted to NICUs in Korea.

Scope of growth factor in cancer patients

The growth factors [GFs] act at different stages of stem cell proliferation. Among them the most important ones found of clinical use are erythropoietin [EPO], granulocyte-colony stimulating factor [G-CSF], granulocyte macrophagecolony stimulating factor [GM-CSF], and thrombopoietin [TPO]. Their concomitant use makes treatment with chemotherapy or radiotherapy easier and cost-effective, with fewer side effects and better quality of life in highly selected patients. This is a review article

Severe chronic neutropenia--a case report.

Severe chronic neutropenia (SCN) is a very rare disease with around 650 people worldwide known to have the condition. SCN is a serous condition with a considerable morbidity and mortality if not treated. We hereby report a case of SCN which had repeated admissions to the hospital with severe neutropenia and high grade fever. We also review the literature elucidating some of the mechanisms and consequences of SCN ( e.g: the neutrophil elastase gene mutations and the risk of progression to myelodysplasia and acute leukemia) and the role of granulocyte-colony stimulating factor.

Severe neutropenia in an infant with methylmalonic acidemia

Neutropenia exists when the neutrophil counts is less than 1000/mm3 in infants between 2 weeks and 1 year of age and less than 1500/mm3 beyond 1 year of age (1). Severe infections occur when the absolute neutrophil count is below 500/mm3 with perirectal abscesses, pneumonia, and sepsis being common. Granulocyte Colony-Stimulating Factor (G-CSF) produces a sustained neutrophil recovery in patients with severe neutropenia, reduces the incidence and severity of infection, and improves the quality of life. Various cytopenias, including neutropenia, thrombocytopenia and pancytopenia, have been reported in association with inborn errors of branched aminoacid metabolism such as methylmalonic, propionic and isovaleric acidemia. We report an infant with methylmalonic acidemia who presented severe neutropenia

Increased levels of multiple forms of dihydrofolate reductase in peripheral blood leucocytes of cancer patients receiving haematopoietic colony-stimulating factors: interim analysis

The precise mechanism whereby granulocytes proliferate when haematopoietic colony stimulating factors (CSFs) are used in neutropenic cancer patients is poorly understood. The purpose of this study was to investigate whether these cytokines bring about leucocyte proliferation by increasing the levels of multiple forms of dihydrofolate reductase (DHFR). Blood samples were collected from 36 cancer patients (25 males and 11 females) with chemotherapy-induced neutropenia. One sample of blood from each patient was obtained before therapy either with CSF, such as granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) or with placebo, and another one at the time of resolution of neutropenia. Peripheral blood leucocytes in these blood samples were counted, separated and lysed. From lysates, cytoplasmic samples were prepared and analyzed for active DHFR by a methotrexate-binding assay and for total immunoreactive DHFR by an enzyme linked immunosorbent assay. The increase in total leucocyte count (TLC) was most prominent (P < 0.005) in the CSF group and less so (P < 0.05) in the placebo group. The mean +/- SD concentration values of active DHFR before and after stimulation with GM-CSF found were to be 0.34 +/- 0.4 ng/mg protein and 0.99 +/- 0.82 ng/mg protein, respectively, and in the group treated with G-CSF, 0.24 +/- 0.32 ng/mg protein and 1.18 +/- 2.4 ng/mg protein, respectively. This increase in active DHFR after stimulation with CSF was statistically significant (P <0.05). Similarly, concentration values of immunoreactive but nonfunctional form of DHFR (IRE) were 110 +/- 97 ng/mg protein and 605 +/- 475 ng/mg protein before and after stimulation with GM-CSF, and 115 +/- 165 ng/mg protein and 1,054 +/- 1,095 ng/ mg protein before and after stimulation with G-CSF. This increase in concentration of IRE after stimulation with GM-CSF or G-CSF was statistically significant (P < 0.005). In the control group, there was an increase in the concentration of both active DHFR and IRE after treatment with placebo. However, this was not statistically significant. Resolution of neutropenia was quicker in the groups treated with CSF compared to the control group. Results of this study indicate that colony stimulating factors (G-CSF and GM-CSF) induce white cell proliferation by increasing the levels of multiple forms of DHFR.

Evaluación del paciente neutropénico con cáncer en pediatría / Evaluation of the neutropenia a patient with neoplasm at paediatric

Una de las principales complicaciones que se presentan como obstáculo en el manejo exitoso de las enfermedades malignas del niño son las infecciones y entre los factores que más predisponen a ellas, se encuentran la neutropenia. Con objeto correlacionar la presencia de infecciones con el grado y duración de la neutropenia, se realizó el seguimiento de 43 pacientes afectados de leucemia y otros tumores, que presentaron 107 episodios de neutropenia, ingresados en el Servicio de Hematología del Hospital Pediátrico "José Luis Miranda durante los años 1992 a 1994. Se analizó el grado y la duración de la neutropenia en leucemias y otros tumores y su correlación con la presencia de infecciones. Se analizó la sintomatología clínica, el tipo de infección y la repuesta a las medidas terapéuticas utilizadas. Se detectó la presencia de infección en 56 episodios de neutropenia (52 por ciento) predominando en las leucemias con relación a otros tumores. Tanto el grado como la duración de la neutropenia fue significativamente superior en las leucemias. La incidencia de infecciones fue mayor en forma significativa, con cifras de neutrofilos inferiores a 500/mm3 y con una duración de la neutropenia superior a 7 días. Los síntomas más frecuentes dependientes de la infección fueron: fiebre, toque del estado general y anorexia; las infecciones principales fueron la sepsis generalizada y las afectaciones respiratorias. El 66 por ciento de los pacientes tuvo buena respuesta a la primera combinación de antibióticos utilizada. La mortalidad fue baja

Neutropenia autoinmune infantil / Autoimmune neutropenia in children

Se describen 15 lactantes que sufrieron neutropenia crónica, con recuentos absolutos de neutrófilos menores a 1 000/µl de sangre al ingreso. En todos los pacientes se efectuaron recuentos de leucocitos y fórmula leucocitaria repetidamente durante la enfermedad, estudio de médula ósea y mediciones de anticuerpos antineutrófilos por inmunofluorescencia indirecta. La mediana de la edad al diagnóstico era 8 meses, márgenes 5 a 18 meses. La enfermedad fue comprobada en todos los pacientes por anticuerpos antineutrófilos circulantes en el suero a titulos entre 1/20 y 1/80. Todos los casos se recuperaron expontáneamente, sin mediar tratamientos "específicos" para la neutropenia, al cabo de 4 a 63 meses, mediana de 15 meses, desde la detección del trastorno. 6 pacientes sufrieron episodios reiteradosde infección durante el curso de la neutropenia, 3 uno sólo. Todos los casos respondieron a los tratamientos convencionales con antibióticos. 6 pacientes fueron asintomáticos. La neutropenia autoinmune es probablemente la causa más frecuente de neutropenia crónica del lactante. Evoluciona en plazos variables a la mejoría espontánea, requiriendo de tratamiento conservador