Clinical tolerability and pharmacokinetics of troxacitabine / 中华肿瘤杂志

Objective: To investigate the safety and efficacy of troxatabine in advanced or relapsed malignant tumors resistant to standard therapy in China. Methods: This is a phase Ⅰ prospective study. During dose escalation, patients in Cancer Hospital, Chinese Academy of Medical Sciences received a single-dose intravenous infusion of troxacitabine. The planned dosing groups were 1.8, 3.6, 4.8, 6.4 and 8.0 mg/m(2) on days 1 and 8 every 3 weeks. The data of all patients were collected for safety analyses. Safety and tolerability were evaluated by monitoring adverse events. Results: Nineteen patients were enrolled from April 2018 to May 2019. The major adverse events were fatigue (89.5%, 17/19), leukopenia (84.2%, 16/19) and neutropenia (78.9%, 15/19). The dose limiting toxicity was neutropenia. The maximum tolerated dose was 6.4 mg/m(2). The best effect was stable disease (43.8%). The half-life of elimination phase from 15.91 hours to 76.63 hours in each dose group. Conclusions: The toxicity of troxacitabine is well tolerant. We recommend that the dose for Phase Ⅱ clinical trial should be 6.4 mg/m(2).

Eficacia y seguridad del tratamiento empírico con piperacilina/tazobactan como monoterapia en episodios de neutropenia y fiebre en niños con cáncer: revisión sistemática y meta-análisis / Efficacy and safety of empirical treatment with piperacillin/tazobactan as monotherapy in episodes of neutropenia and fever in children with cancer: systematic review and meta-analysis

INTRODUCCIÓN: La neutropenia febril en niños con patología oncohematològica requiere un tratamiento empírico precoz y adecuado. Esta revisión sistemática se realizó para evaluar si piperacilina/tazobactam (PTZ) monoterapia es más efectiva y segura que los comparadores, en niños con episodios de neutropenia febril de causa oncológica. MATERIAL Y MÉTODOS: Se realizó una búsqueda bibliográfica en Embase, MEDLINE utilizando los términos de búsqueda (('febrile neutropenia' OR hemato oncology OR haemato oncology OR 'immunocompromised host' OR 'immunocompromised patient' OR 'chemotherapy-induced febrile neutropenia') AND (piperacillin OR tazobactam OR 'piperacillin plus tazobactam' OR 'piperacillin/tazobactam' OR 'piperacillin-tazobactam' OR tazocin OR 'piperacillin-tazobactam drug combination')). El criterio de valoración de eficacia fue la incidencia de fracaso terapéutico. El punto final de seguridad fue la ausencia de cualquier efecto adverso (EA). RESULTADOS: Se identificaron 1.388 estudios, de los cuales se incluyeron 11 que cumplían los criterios de elegibilidad. Los estudios presentaron notable homogeneidad ( I 2 0%) y no se detectó sesgo de publicación (p 0,36). El riesgo de fracaso terapéutico de PTZ no fue mayor que en los comparadores (RR global: 0,94; IC95% 0,83 a 1,07) como tampoco lo fue, la incidencia de EA. CONCLUSIONES: El riesgo de fracaso terapéutico no fue superior para la PTZ como monoterapia frente a los comparadores

BACKGROUND: Febrile neutropenia in children with onco-hematological diseases is an important cause of morbidity and mortality and requires early and adequate empirical treatment. This systematic review was conducted to evaluate if piperacillin/ tazobactan (PTZ) monotherapy leads to a lower incidence of therapeutic failures than comparators. METHODS: A literature search was carried out in Embase, and MEDLINE databases using the search terms ('febrile neutropenia' OR hemato oncology OR haemato oncology OR 'immunocompromised host' OR 'immunocompromised patient' OR 'chemotherapy-induced febrile neutropenia') AND (piperacillin OR tazobactam OR 'piperacillin plus tazobactam' OR 'piperacillin/tazobactam' OR 'piperacillin-tazobactam' OR tazocin OR 'piperacillin-tazobactam drug combination')), Efficacy endpoint was treatment failure rate. The safety end-point was absence of any adverse effects (AE). RESULTS: Eleven studies were included. No heterogeneity was detected ( I 2 0%). The risk of failure was not superior for piperacillin/tazobactan to comparators (Global RR: 0.94; IC95% 0.83 a 1.07). Rates of adverse events were similar among studies. No publication bias was detected (p 0.36). CONCLUSIONS: This systematic review and meta-analysis showed that treating episodes of febrile neutropenia in oncology pediatric patients, the risk of failure for PTZ was not superior to comparators. Adverse events were similar to the comparators.

Neutropenia febril asociada a la ingesta de metimazol: reporte de caso / Febrile neutropenia associated with methimazole ingestion: case report

La neutropenia se define como un recuento absoluto de neutrófilos menor a 1500 células /µL. Se debe a la disminución en la producción de granulocitos o al aumento en su destrucción, ya sea a nivel medular o periférico. Según la clasificación de la Organización Mundial de la Salud (OMS) los grados de neutropenia van de 0 a IV, de acuerdo a la magnitud de la disminución del recuento de neutrófilos. El grado IV es el de mayor riesgo y corresponde a recuentos por debajo de 500 células/µL. El impacto en la morbimortalidad asociada a la neutropenia no está vinculado con la disminución directa del recuento celular, sino con los procesos infecciosos asociados a los que son propensos los pacientes que la presentan. Existen diversas condiciones por las que se puede desarrollar neutropenia, entre las que se encuentran las infecciones, las malignidades y los fármacos. Estos últimos pueden generar eventos adversos por mecanismos dosis dependiente, como en el caso de la quimioterapia citotóxica o por una reacción idiosincrática. Se presenta el caso de una paciente femenina de 37 años de edad, con antecedentes de tirotoxicosis, tratada con propanolol y metimazol durante cuatro semanas, quien además de manifestaciones tóxicas, presentó neutropenia febril muy grave, que mejoró luego de suspensión del antitiroideo. Se pretende resaltar la asociación de neutropenia febril como complicación de uso de tionamidas y la importancia del seguimiento con exámenes de laboratorios para un diagnóstico oportuno(AU)

Neutropenia is defined as an absolute neutrophil count less than 1500 cells / μL. It is due to the decrease in the production of granulocytes or increase in their destruction, either at the medullary or peripheral level. According to the classification of the World Health Organization (WHO) the degrees of neutropenia range from 0 to IV, taking into account the magnitude of the decrease in the neutrophil count. Grade IV is the highest risk and corresponds to counts below 500 cells /μL. The impact on morbidity and mortality associated with neutropenia is not linked to the direct reduction of the cell count, but to the associated infectious processes to which patients who present it are prone. There are several conditions under which neutropenia can develop, including infections, malignancies and drugs. The latter can generate adverse effects by dose-dependent mechanisms, as in the case of cytotoxic chemotherapy or an idiosyncratic reaction. Next, the case of a female patient of thirty-seven years of age, with a history of thyrotoxicosis, treated with propanolol and methimazole for four weeks, who in addition to toxic manifestations, presents very severe febrile neutropenia that improves after suspension of the antithyroid. We aim to highlight the association of febrile neutropenia as a complication of thionamide use and the importance of follow-up with laboratory tests for an opportune diagnosis(AU)

Neutropenia asociada al uso de cefepime en pacientes pediátricos con fibrosis quística / Neutropenia associated with the use of cefepime in pediatric patients with cystic fibrosis

Resumen Las exacerbaciones pulmonares de causa infecciosa son una de las mayores complicaciones en los pacientes con fibrosis quística (FQ). Estas se asocian a un progresivo aumento en la morbilidad y mortalidad. El tratamiento antimicrobiano se realiza dependiendo del microorganismo aislado. Con frecuencia se utilizan antimicrobianos β-lactámicos, los cuales no están exentos de reacciones adversas. A continuación, se describen dos casos de neutropenia tras el uso prolongado de cefepime en pacientes con FQ.

Pulmonary exacerbations of infectious cause are one of the major complications in patients with cystic fibrosis (CF). These are associated with a progressive increase in morbidity and mortality. The treatment depending on the isolated microorganism. The β-lactam antibiotics are generally used which are not exempt from adverse reactions. Next, two report of neutropenia cases are described after prolonged use of cefepime in CF patients.

A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients

OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI) for the rate of neutropenia between the two groups (12.61%) was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety. CONCLUSION: The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisa’s approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima¯).

Hematological and dermatological adverse events during hepatitis C treatment with peg-interferon and ribavirin / Eventos adversos hematológicos e dermatológicos durante o tratamento da hepatite C com interferon peguilado e ribavirina

Objective: To evaluate frequency and impact of adverse events, mainly the hematological and dermatological ones, on sustained virological response, and compliance to hepatitis C treatment. Methods: Patients were treated according to the guidelines of the Brazilian Ministry of Health. Variables associated with hematological and dermatological adverse events were: age, gender, stage of fibrosis, type of Pegylated interferon, dose reductions, temporary discontinuation and early interruption of treatment. Results: Two hundred and twenty two patients were studied (58% females; age 49±11 years). Dose reductions, temporary interruptions, and early discontinuations were observed in 21%, 8% and 9.5% of patients, respectively. The main adverse events were hematological (anemia, neutropenia and thrombocytopenia) and dermatological (pruritus and alopecia). Anemia (Hemoglobin <10g/dL) was associated with female gender (p<0.001), advanced fibrosis (p=0.047) and dose reductions (p<0.001); neutropenia with advanced fibrosis (p=0.003) and temporary discontinuation (p=0.002); thrombocytopenia with advanced fibrosis (p<0.001) and pegylated interferon α2a (p=0.05). Pruritus and alopecia were associated to female gender (p=0.008 and p=0.02) and treatment interruption (p=0.029 and p=0.02).Conclusion: Hematological and dermatological adverse events are frequent in hepatitis C patients treated with pegylated interferon and ribavirin. However, despite frequent dose reductions and interruptions, these adverse events did not affect the sustained virological response.

Objetivo: Avaliar a frequência e o impacto de eventos adversos, principalmente hematológicos e dermatológicos, na resposta virológica sustentada e na aderência ao tratamento para hepatite C. Métodos: Os pacientes foram tratados de acordo com diretriz do Ministério da Saúde. Variáveis associadas com eventos adversos hematológicos e dermatológicos foram: idade, sexo, grau de fibrose, tipo de interferon peguilado, reduções de dose, descontinuação temporária e interrupção precoce do tratamento. Resultados: Foram estudados 232 pacientes (58% mulheres; idade 49±11 anos). Reduções de dose, interrupções temporárias e descontinuações precoces foram observadas em 21%, 8% e 9,5% dos pacientes, respectivamente. Os principais eventos adversos foram hematológicos (anemia, neutropenia e plaquetopenia) e dermatológicos (prurido e alopecia). Anemia (hemoglobina <10g/dL) se associou a sexo feminino (p<0,001), fibrose avançada (p=0,047) e reduções de doses (p<0,001); neutropenia com fibrose avançada (p=0,003) e interrupção temporária (p=0,002); plaquetopenia com fibrose avançada (p<0,001) e interferon peguilado α2a (p=0,05). Prurido e alopecia se associaram ao sexo feminino (p=0,008 e p=0,02) e interrupção do tratamento (p=0,029 e p=0,02). Conclusão: Eventos adversos hematológicos e dermatológicos foram frequentes em pacientes tratados com interferon peguilado e ribavirina. Entretanto, a despeito de frequentes reduções de dose e interrupções, estes eventos adversos não afetaram a resposta virológica sustentada.

Pharmacovigilance of patients with multiple myeloma being treated with bortezomib and/or thalidomide

In order to evaluate the main adverse effects of drug protocols using bortezomib and/or thalidomide for the treatment of multiple myeloma, we conducted a prospective study. Data were collected through interviews, clinical observation, and from hospital records. A total of 59 patients were included. There was a predominance of females, 36 (61%) vs 23 (39%) males, and of whites, 49 (83.1%) vs 10 (16.9%) blacks. Age ranged from 40 to 94 years, with a median of 65 years (SD=11.6). Regarding staging at diagnosis, 27 (45.7%) patients were in stage III-A, with 12 (20.3%) patients having serum creatinine ≥2 mg/dL. The main adverse effects in the bortezomib treatment group (n=40) were: neutropenia (42.5%), diarrhea (47.5%), and peripheral neuropathy in 60% of cases, with no difference between the iv (n=26) and sc (n=14) administration routes (P=0.343). In the group treated with thalidomide (n=19), 31.6% had neutropenia, 47.4% constipation, and 68.4% peripheral neuropathy. Neutropenia was associated with the use of alkylating agents (P=0.038). Of the 3 patients who received bortezomib in combination with thalidomide, only 1 presented peripheral neuropathy (33.3%). Peripheral neuropathy was the main adverse effect of the protocols that used bortezomib or thalidomide, with a higher risk of neutropenia in those using alkylating agents. Improving the identification of adverse effects is critical in multiple myeloma patient care, as the patient shows improvements during treatment, and requires a rational and safe use of medicines.

Neutropenia grave secundaria al tratamiento médico de una adenitis por micobacterias no tuberculosas / Severe neutropenia as side effect of medical treatment in nontuberculous mycobacterial adenitis

Non-tuberculous mycobacterial adenitis is getting more common in our environment. Epidemiologic studies and clinical trials published nowadays are limited. We present a 2-years-old boy diagnosed of Mycobacterium intracellulare adenitis and severe neutropenia as side effect of combined treatment with oral azythromycin and rifabutin, which recovers after suspending the second one. Liver metabolism of macrolide seems to increase other drugs toxicity, in this case, rifabutin. The patient eventually needed surgery due to persistence of the adenitis despite treatment with antibiotics.

Las adenopatías por micobacterias no tuberculosas (AMNT) son cada vez más frecuentes en nuestro medio. Los estudios epidemiológicos y ensayos clínicos controlados publicados hasta la fecha son escasos. Presentamos el caso de un niño de 2 años con el diagnóstico de una adenitis por Mycobacterium intracellulare que desarrolló una neutropenia grave secundaria a la terapia combinada de azitromicina y rifabutina oral. La metabolización hepática de los macrólidos parece aumentar la toxicidad de otros fármacos, en este caso, la rifabutina. Finalmente, al paciente se le realizó una exéresis quirúrgica por persistencia de la adenitis a pesar de la antibioterapia.

Neutropenia: occurrence and management in women with breast cancer receiving chemotherapy / Neutropenia: ocorrência e manejo em mulheres com câncer de mama em quimioterapia / Neutropenia: ocurrencia y manejo en mujeres con cáncer de mama en quimioterapia

OBJECTIVES: to identify the prevalence, and describe the management of, neutropenia throughout the chemotherapy treatment among women with breast cancer. METHODS: observational study, cycles of chemotherapy. 116 neutropenic events were recorded, and 63.3% of the patients presented neutropenia at some point of their treatment, 46.5% of these presenting grade II. The management used was temporary suspension between the cycles and the mean number of delays was 6 days. The study was prospective and longitudinal, where the evaluation of the hematological toxicities was undertaken at each cycle of chemotherapy, whether neoadjuvant or adjuvant. RESULTS: 79 women were included, who received 572 cycles. However, the reasons for the suspensions were the lack of a space in the chemotherapy center, followed by neutropenia. CONCLUSION: neutropenia is one of the most common and serious adverse events observed during the chemotherapy. Nursing must invest in research regarding this adverse event and in management strategies for organizing the public health system, so as to offer quality care. .

OBJETIVOS: identificar a prevalência e descrever o manejo de neutropenia ao longo do tratamento quimioterápico, entre mulheres com câncer de mama. MÉTODOS: estudo observacional, ciclos de quimioterapia. Registraram-se 116 eventos neutropênicos e 63,3% das pacientes apresentaram neutropenia em algum momento do tratamento, sendo que 46,5% desses foram de grau II. O manejo utilizado foi a suspensão temporária entre os ciclos e a média de atrasos foi de 6, prospectivo, longitudinal, onde foi realizada a avaliação das toxicidades hematológicas, a cada ciclo de quimioterapia, neoadjuvante ou adjuvante. RESULTADOS: foram incluídas 79 mulheres submetidas a 572 ciclos de quimioterapia. Registraram-se 116 eventos neutropênicos e 63,3% das pacientes apresentaram neutropenia em algum momento do tratamento, sendo que 46,5% desses foram de grau II. O manejo utilizado foi a suspensão temporária entre os ciclos e a média de atrasos foi de 6. .

OBJETIVOS: identificar la prevalencia y describir el manejo de la neutropenia a lo largo del tratamiento quimioterapéutico entre mujeres con cáncer de mama. MÉTODOS: estudio observacional, ciclos de quimioterapia. Se registraron 116 eventos neutropénicos y 63,3% de las pacientes presentaron neutropenia en algún momento del tratamiento, siendo que 46,5% de estos fueron de grado II. El manejo utilizado fue la suspensión temporaria entre los ciclos y el promedio de atrasos fue de 6 días. Estudio prospectivo, longitudinal en donde fue realizada la evaluación de las toxicidades hematológicas, a cada ciclo de quimioterapia, neoadyuvante o adyuvante. RESULTADOS: fueron incluidas 79 mujeres sometidas a 572 ciclos. Sin embargo, los motivos de las suspensiones fueron la falta de cupo en la central de quimioterapia seguido por la neutropenia. CONCLUSIÓN: la neutropenia es uno de los eventos adversos más comunes y graves observados durante la quimioterapia. La enfermería debe realizar inversiones para investigar este evento adverso y para proponer estrategias de gestión para organizar el sistema público de salud, ofreciendo así una asistencia de calidad. .

Epidemiología de la neutropenia febril en pacientes adultos con neoplasia hematológica, en un período de 26 meses en el Hospital Pablo Tobón Uribe, Colombia / Epidemiology of febrile neutropenia in adult patients with hematologic neoplasms in a period of 26 months in Hospital Pablo Tobón Uribe, Colombia

Background: Febrile neutropenia (FN) is a significant adverse effect post-chemotherapy due to its high morbidity and mortality. There are few studies in our country with these kind of patients. Objective: To describe the characteristics and mortality in patients with hematologic neoplasms who developed FN post-chemotherapy. Methodology: A descriptive case series in patients with hematologic neoplasms who developed FN post-chemotherapy in Hospital Pablo Tobón Uribe. Results: 101 episodes of FN in 43 patients. The median age was 44 years. 63.5% of patients had no apparent clinical focus of infection at admission, 11.8% had soft tissue compromise and 8.9% urinary tract infection. Bacteremia was documented in 41.5% and catheter-associated bacteremia in 3.9%. The most common organisms were Escherichia coli 43.4%, Klebsiella pneumoniae 17.3% and Staphylococcus aureus 8.6%. Of those isolated in blood 84.7% were Gram negative rods and 15.2% were Gram positive bacteria. Piperacillin/tazobactam was the most common empirically prescribed antibiotic (81.1%). Mortality of FN episodes occurred in 8 (7.92%) patients, 5 (62.5%) attributable to infection and 3 (37.5%) due to progression of hematologic malignancy with a resolution of FN. Conclusions: In our case series of FN the microbiological characteristics differed significantly from developed countries, but a similar mortality rate per episode was observed.

Introducción: La neutropenia febril (NF) es un efecto adverso importante post-quimioterapia por su alta morbi-mortalidad. Hay pocos estudios en nuestro entorno con estos pacientes. Objetivo: Describir las características de los pacientes adultos con neoplasia hematológica que desarrollaron NF post-quimioterapia. Metodología: Estudio descriptivo de serie de casos, en pacientes con neoplasia hematológica y NF post-quimioterapia en el Hospital Pablo Tobón Uribe. Resultados: Ciento un episodios de NF en 43 pacientes con una mediana de edad de 44 años. El 63,5% no tenían foco infeccioso clínico aparente al ingreso, 11,8% tenía compromiso de tejidos blandos y 8,9% foco urinario. Se documentó bacteriemia primaria en 42 (41,5%) y bacteriemia asociada al catéter en 4 (3,96%). Los microorganismos más frecuentes fueron Escherichia coli 43,4%, Klebsiella pneumoniae 17,3% y Staphylococcus aureus 8,69%. De los aislados en sangre, 84,7% fueron bacilos gramnegativos y 15,2% cocáceas grampo-sitivas. Piperacilina/tazobactam fue la antibioticoterapia empírica inicial en 81,1% de los episodios. La mortalidad por episodios de NF fue de 7,92%, en 62,5% atribuible a la infección y en el resto a progresión de la neoplasia hematológica con resolución de la NF. Conclusión: Serie de casos de NF con características microbiológicas que difieren significativamente a los países desarrollados, pero con una mortalidad por episodios similar.

Factor estimulante de colonias de granulocitos en pacientes con cáncer / Granulocyte-colony stimulating factor in patients with cancer

Se efectuó un estudio descriptivo, longitudinal y prospectivo de 26 pacientes con cáncer en diferentes localizaciones asociado a leucopenia y neutropenia inducidas por citotóxicos, atendidos en el Servicio de Quimioterapia del Hospital Oncológico Docente Conrado Benítez de Santiago de Cuba, de mayo del 2011 a igual mes del 2012, con vistas a determinar el efecto del factor de colonias granulocítica recombinante Ior® LeukoCIM --producido por el Centro de Inmunología Molecular de Ciudad de La Habana-- en ellos mediante la realización de conteos globales de leucocitos y neutrófilos, antes y después de aplicar el tratamiento. En la serie predominaron el sexo femenino, el cáncer de mama y el estadio clínico II; también se obtuvo que 92,3 por ciento de los pacientes respondieron satisfactoriamente a la terapia, el estadio clínico del cáncer no modificó el efecto mielodepresor de los citotóxicos ni el mieloestimulador de la hormona, y el cisplatino y la adriamicina se relacionaron con las neutropenias mayores y la falta de reacción al factor. Para finalizar, el Ior® LeukoCIM estimuló el sistema granulopoyético de la mayoría de los afectados

A descriptive, longitudinal and prospective study was conducted in 26 patients with cancer in different locations associated with leukopenia and neutropenia induced by cytotoxic drugs, treated at the Chemotherapy Department of Conrado Benítez Teaching Oncology Hospital of Santiago de Cuba, from May 2011 to the same month of 2012, with the purpose of determining the effect of the recombinant granulocyte-colony factor Ior® LeukoCIM --produced by the Center of Molecular Immunology in Havana city-- in them by means of global counts of leukocytes and neutrophils before and after applying the treatment. Female sex, breast cancer and clinical stage II prevailed in the series. It was also found that 92.3 percent of patients responded successfully to the therapy, the clinical stage of cancer did not modify the myelosuppressive effect of cytotoxic drugs nor the myelostimulating effect of hormone, and cisplatin and adriamycin were related to higher neutropenia and lack of reaction to the factor. Finally, the Ior® LeukoCIM stimulated the granulopoietic system of most patients

Aspergilosis pulmonar secundaria a neutropenia inducida por metimazol: reporte de un caso / Pulmonary aspergillosis due to methimazole-induced neutropenia: a case report

Se reporta el caso de una paciente de 48 años de edad con diagnóstico reciente de enfermedad de Graves, quien acudió a emergencia por presentar fiebre, palpitaciones y dolor faríngeo. Su tratamiento regular incluía metimazol. Al ingreso, los análisis mostraron TSH suprimido, T4 libre elevado y neutropenia. La paciente fue hospitalizada, se administraron antibióticos y factor estimulante de colonia. Después de diez días de tratamiento, la paciente presentó leucocitosis, fiebre y hemoptisis. La tomografía de tórax mostró una cavidad con múltiples nódulos en el lóbulo superior derecho. Los cultivos fueron positivos a Aspergillus fumigatus y Aspergillus flavus. Se inició tratamiento con anfotericina B y luego se cambió a voriconazol, a pesar de lo cual no hubo mejoría del cuadro. La paciente falleció por falla multiorgánica.

A 48-year old woman with a recent diagnosis of Graves’ disease arrived at the emergency room with fever, palpitations, and a sore throat. Her regular treatment included methimazole. On admission, laboratory results showed suppressed TSH, elevated free thyroxine, and neutropenia. She was admitted and started on antibiotics and granulocyte-macrophage colony stimulating factor (gm-csf). After ten days, the patient developed leukocytosis, fever, and hemoptysis. Chest CT scan showed a lung cavity with multiple nodules in the upper right lobe. Cultures from a lung biopsy were positive for Aspergillus Fumigatus and Aspergillus Flavus. Amphotericin B was started but then switched to voriconazole, with both treatments failing to result in clinical improvement. The patient died of multi-organ failure.

Resultados de profilaxis con itraconazol 800 mg/día vía oral en adultos con leucemia aguda y neutropenia de alto riesgo: Hospital del Salvador 2006-2008 / Itraconazole 800 mg for the prophylaxis of fungal infections in patients with acute leukemia and severe neutropenia

Background: Systemic fungal infections and specifically invasive aspergillosis (IA) are associated with a high morbi-mortality rate in patients with hematologic malignancies. Itraconazole kinetic studies show that plasma levels are not satisfactory, even though there is a reduction of the severity in clinical cases. Aim: To evaluate the results of oral prophylaxis with high dose itraconazole, 400 mg bid, among patients with adult acute leukemia. Material and Methods: Prospective analysis of 93 high risk febrile episodes (with an absolute neutrophil count of less than 500 x mm3 for more 10 days), that occurred in 76 patients. Results: Seventy five percent of episodes occurred in patients with acute myeloid leukemia and 25 percent in patients with acute lymphoblastic leukemia. Fifty two percent occurred during the induction of chemotherapy. Median duration of severe neutropenia was 21 days (range 10-48). Median duration of itraconazole prophylaxis was 17 days (range 6-34). A low frequency of invasive fungal infections was observed (17 percent). According to diagnostic criteria, 5 percent of episodes corresponded to persistent fever , 1 percent and 11 percent of episodes, to probable or possible IA, respectively. No confirmed or proven IA was observed. Mortality of IA was 18 percent. No serious adverse events due to itraconazole were observed. Conclusions: The use of high dose itraconazole prophylaxis in adult patients with acute leukemia and severe neutropenia was associated to low incidence and mortality of invasive mycoses.

Miliaria-rash after neutropenic fever and induction chemotherapy for acute myelogenous leukemia / Miliária 'rash' após neutropenia febril e quimioterapia de indução para a leucemia mielóide aguda

Miliaria is a disorder of the eccrine sweat glands which occurs in conditions of increased heat and humidity. It can be associated with persistent febrile states as well as with certain drugs. We presented a 40 year-old female with myelodysplastic syndrome and progression to acute myelogenous leukemia who was admitted to the hospital for chemotherapy induction. The patient was treated with idarubicin and cytarabine. She became pancytopenic and developed neutropenic fever and was started on vancomycin and cefepime, but was persistently febrile with night sweats. Five days into her fevers, she developed diffuse, nonpruritic and fragile vesicles together with drenching nightsweats. The patient's exanthem was diagnosed as Miliaria crystallina, most probably induced by neutropenic fever and idarubucin exposure.

Miliária é uma desordem das glândulas sudoríparas écrinas, que ocorre em condições de aumento de calor e umidade. Miliária pode ser associada com estados febris persistentes bem como com certos medicamentos. Apresentamos o caso de uma mulher de 40 anos com síndrome mielodisplásica e progressão para leucemia mielóide aguda que foi admitida no hospital para quimioterapia de indução. A paciente foi tratada com idarrubicina e citarabina. Ela se tornou pancitopênica e desenvolveu neutropenia febril. Iniciou tratamento com vancomicina e cefepime, mas a febre com sudorese noturna continou. Cinco dias depois a paciente desenvolveu vesículas difusas, não pruríticas e frágeis juntamente com a persistência de sudorese noturna. O exantema do paciente foi diagnosticado como Miliária cristalina, provavelmente induzida por neutropenia febril e exposição a idarubucin.

Acute promyelocytic leukemia: An experience from a tertiary care centre in north India.

Background: There are very limited data reported about acute promyelocytic leukemia (APL) from developing countries. We reviewed the clinical course and treatment outcome of APL patients treated at our center. Materials and Methods: Between January 1997 and December 2007, 33 patients with APL received induction therapy using ATRA + daunorubicin (n = 26), As = 26), As2O3 (n = 4) or daunorubicin + cytosar ( n = 3). Results: Median age was 30 years with a male to female ratio of 1.68. Twenty seven patients (82%) achieved CR. Complications during induction therapy were febrile neutropenia (33%), ATRA syndrome (30%), bleeding (58%), and diarrhea in (6%) patients. During induction and follow up, 8 (24.24%) patients died, 6 (18.18%) during induction, 1 (3%) during maintenance, and 1 (3%) after relapse. Median OS is 128 months while median EFS is 61 months. Four patients relapsed at a median time of 61 months. At the time of censoring, 25 patients were alive at a median follow up of 13 months (range 0.6 -127 months); 21 in CR1, 3 in CR2, 1 in CR3. Comparisons among the risk groups (CR and relapse rate and survival statistics) were not statistically significant. Conclusions: APL is a highly curable malignancy. Our results confirm the findings of the published literature from larger cooperative studies from the West. We may further improve outcome with quicker diagnosis and more efficient supportive care system.

Ocorrência de neutropenia em mulheres com câncer de mama durante tratamento quimioterápico / Occurrence of neutropenia in women with breast cancer during chemotherapy treatment

OBJETIVO: Analisar a ocorrência de neutropenia induzida por drogas utilizadas no tratamento quimioterápico de mulheres com câncer de mama. MÉTODOS: Estudo retrospectivo, com avaliação de 72 prontuários, durante 2003-2006. RESULTADOS: Dos 558 ciclos de quimioterapia realizados, foram registrados 152 eventos adversos nos períodos de neoadjuvância e adjuvância, totalizando 43 casos por toxicidade hematológica. Quanto à ocorrência de neutropenia, 43 por cento apresentaram, pelo menos, um episódio durante o tratamento. Testes de hipótese para comparar as médias dos valores de glóbulos brancos entre as mulheres que apresentaram ou não neutropenia apontaram para valores estatisticamente significantes, nos ciclos dois e três da neoadjuvância e nos ciclos dois, três e quatro da adjuvância. CONCLUSÃO: A neutropenia, tanto na neoadjuvância como na adjuvância ocorreu a partir do segundo ciclo e manteve-se durante o tratamento e foi estatisticamente significante quando foram compadas as mulheres que tiveram ou não esta ocorrência.

OBJECTIVE: To analyze the occurrence of neutropenia induced by drugs used in chemotherapy treatment for women with breast cancer. METHODS: Retrospective study, with assessment of 72 records, between 2003-2006. RESULTS: Of the 558 cycles of chemotherapy performed, there were 152 adverse events registered in adjuvant and neoadjuvant therapy periods, totaling 43 cases of haematological toxicity. Regarding the occurrence of neutropenia, 43 percent had at least one episode during treatment. Hypothesis tests to compare the mean values of white blood cells from women who did or did not present with neutropenia pointed to statistically significant values in cycles two and three of neoadjuvant therapy and in cycles two, three and four in the adjuvant therapy. CONCLUSION: Neutropenia in both the adjuvant and neoadjuvant therapy occurred beginning with the second cycle and was maintained during treatment, and was statistically significant when compared women who had to those who did not have this occurrence.

OBJETIVO: Analizar la ocurrencia de neutropenia inducida por drogas utilizadas en el tratamiento quimioterápico de mujeres con cáncer de mama. MÉTODOS: Estudio retrospectivo, realizado con la evaluación de 72 historias clínicas, durante loa años 2003-2006. RESULTADOS: De los 558 ciclos de quimioterapia realizados, fueron registrados 152 eventos adversos en los períodos de neoadyuvante y adyuvante, totalizando 43 casos por toxicidad hematológica. En cuanto a la ocurrencia de neutropenia, el 43 por ciento presentaron, por lo menos, un episodio durante el tratamiento. Las pruebas de hipótesis para comparar los promedios de los valores de glóbulos blancos entre las mujeres que presentaron o no neutropenia apuntaron hacia valores estadísticamente significativos, en los ciclos dos y tres de la neoadyuvancia y en los ciclos dos, tres y cuatro de la adyuvancia. CONCLUSIÓN: La neutropenia, tanto en la neoadyuvancia como en la adyuvancia ocurrió a partir del segundo ciclo y se mantuvo durante el tratamiento y fue estadísticamente significativa cuando fueron compadas las mujeres que tuvieron o no esta ocurrencia.

Pathology in children of HIV women.

Objective. To assess the frequency of perinatal pathology in children exposed to antiretrovirals in perinatal period. Methods. Retrospective observational cohort study. Data collected among uninfected children born to HIV-infected women followed up from 1994 to 2006 in a tertiary Hospital. 220 uninfected children were studied. Factors studied included maternal, obstetrical and pediatric variables. Results. The most common disorder found among children exposed to antiretroviral drugs was anemia (84%); 6,4% of children had neutropenia and more than 24% had thrombocytosis, a finding never described before. Prematurity (24%) and low birth weight (23.6%) rates were high. Several congenital malformations were found: Poland syndrome, angiomas, hypospadias, Pierre-Robin sequence, trisomy 8, craniostosis and others. Long-term follow-up revealed neurological, cardiological and ophthalmological pathologies. Conclusion. Some pathologies are frequent among children exposed to antiretroviral agents during perinatal life. It is crucial to carry out long-term studies to assess the safety of this therapy.

Antibiotic-induced Severe Neutropenia with Multidrug-Dependent Antineutrophil Antibodies Developed in A Child with Streptococcus pneumoniae Infection

Drug-induced neutropenia (DIN), particularly that in which antibiotic-dependent antineutrophil antibodies have been detected, is a rare disorder. We report the case of a child with pneumococcal pneumonia, who experienced severe neutropenia during various antibiotic treatments. We detected 4 kinds (cefotaxim, augmentin, vancomycin, and tobramycin) of antibiotic-dependent antineutrophil antibodies by using the mixed passive hemagglutination assay (MPHA) technique with this child.

Role of granulocyte colony stimulating factor (G-CSF) in chemotherapy induced neutropenia.

BACKGROUND: In the past decade, there have been many clinical trials investigating the potential benefits of adjunctive therapy with colony stimulating factors (CSFs) both to ameliorate or prevent profound neutropenia and its potentially life threatening consequences. Neutropenia is the most common dose limiting side effects of cytotoxic chemotherapy. We decided to study the effect of same in our patients coming to haematology clinic. AIMS AND OBJECTIVES: To see the effect of G-CSF on severity of neutropenia following chemotherapy in patients of haematological malignancies and to see the effect of G-CSF on duration of hospitalization, documented infections and duration of fever as compared to control group in patients with neutropenia following chemotherapy in haematological malignancies. MATERIAL AND METHODS: Thirty patients of acute leukemia were prospectively studied. Patients were given G-CSF 24.hours following chemotherapy induced neutropenia and following parameters were observed. (a) median time to ANC recovery (b) incidence and duration of fever (c) duration of hospitalization following chemotherapy (d) incidence of documented infections. The patients were given G-CSF until the neutrophil count was >1000/ml for 3 days or maximum of 7 days. RESULTS: Mean age was 29.33 +/- 14 years in G-CSF group and 27.53 +/- 13.75 in control group. Mean duration of neutropenia was 11.4 days (p < 0.05) in G-CSF group and 15.8 days in control group. Mean duration of fever was 8.2 days in G-CSF group and 13.53 days in control group (p < 0.05). Mean duration of hospital stay was 21.33 days in G-CSF group and 25 days in control group (p > 0.05). CONCLUSIONS: The study demonstrates that G-CSF administration is efficacious in chemotherapy induced neutropenia by decreasing the duration of neutropenia and duration of fever.