Impacto clínico de la profilaxis con levofloxacino en pacientes neutropénicos con neoplasias hematológicas Estudio antes y después, en un hospital de cuarto nivel de Colombia / Clinical impact of levofloxacin prophylaxis in neutropenic patients with hematological malignancies Before and after study in a fourth-level Colombian hospital

Resumen Introducción: el uso de la profilaxis con fluoroquinolonas en pacientes con neutropenia y enfermedades hematológicas malignas es controvertido. Se ha reportado un impacto positivo en la reducción de la morbilidad y mortalidad, pero el consiguiente desarrollo de resistencia bacteriana es una preocupación. Objetivo: comparar la incidencia de neutropenia febril, infección documentada y muerte por infección, en una cohorte de pacientes adultos con neoplasias hematolinfoides en quimioterapia de alto riesgo, que reciben profilaxis con levofloxacino, versus quienes no recibieron profilaxis. Material y métodos: s e realizó un estudio de antes y después. Los desenlaces fueron neutropenia febril, infección clínica y microbiológicamente documentada, duración de la hospitalización, estancia en la unidad de cuidados intensivos, y mortalidad asociada a infección. Resultados: ciento sesenta y ocho (168) admisiones hospitalarias, 98 en el grupo con levofloxacino y 70 en grupo sin profilaxis. El grupo de levofloxacino tuvo reducción de eventos de neutropenia febril (39 vs 70%, p=<0,001), menor tasa de infecciones microbiológicamente documentadas (45.6 vs 61,2%, p= 0.049), menor estancia hospitalaria (24 vs 28.1 días, p=0.008), y menor estancia en la unidad de cuidados intensivos (17 vs 6.1%, p=0.023), comparado con el grupo sin profilaxis. Se encontró asociación en la administración de levofloxacino y reducción de eventos de neutropenia febril OR= 0.21 (IC 95% 0.10-0.43), NNT= 3 (IC 95% 2-6). No se documentó diferencia en la mortalidad (3 vs 8.6%, p=0.118). Conclusiones: la profilaxis mostró beneficio en reducción de eventos febriles, infección micro-biológicamente documentada, menor estancia hospitalaria y en la unidad de cuidados intensivos, sin impacto en la mortalidad. (Acta Med Colomb 2016; 40: 235-242).

Abstract Introduction: the use of fluoroquinolone prophylaxis in patients with neutropenia and hematological malignancies is controversial. A positive impact on reducing morbidity and mortality has been reported, but the subsequent development of bacterial resistance is a concern. Objective: to compare the incidence of febrile neutropenia, documented infection and death from infection in a cohort of adult patients with hematolymphoid neoplasms on high-risk chemotherapy that receive prophylaxis with levofloxacin versus those who did not receive prophylaxis. Material and methods: a before and after study was performed. Outcomes were febrile neutropenia, clinically and microbiologically documented infection, duration of hospitalization, intensive care unit stay, and mortality associated with infection. Results: one hundred sixty-eight (168) hospital admissions, 98 in the levofloxacin group and 70 in the non-prophylaxis group. The levofloxacin group had a reduction in febrile neutropenia events (39 vs 70%, p = <0.001), a lower rate of microbiologically documented infections (45.6 vs 61.2%, p = 0.049), shorter hospital stay (24 vs. 28.1 days , P = 0.008), and shorter stay in the intensive care unit (17 vs 6.1%, p = 0.023) compared to the group without prophylaxis. Association in the administration of levofloxacin and reduction of febrile neutropenia events OR = 0.21 (95% CI 0.10-0.43), NNT = 3 (95% CI 2-6) was found. There was no documented difference in mortality (3 vs 8.6%, p = 0.118). Conclusions: prophylaxis showed benefit in reducing febrile events, microbiologically documented infection, less hospital and intensive care unit stay, with no impact on mortality. (Acta Med Colomb 2016; 40: 235-242).

Diagnóstico de imunofenótipos de síndromes linfoproliferativas crônicas por citometria de fluxo na Fundação HEMOPA / Diagnosis of immunophenotyping of chronic lymphoproliferative syndromes by flow cytometry at HEMOPA blood center

INTRODUÇÃO: As síndromes linfoproliferativas formam um grupo heterogêneo de neoplasias malignas com diferentes comportamentos clínicos, fatores patológicos e características epidemiológicas e podem ter seu diagnóstico geral com base na morfologia das células linfoides observadas no sangue periférico. OBJETIVO: Testar a factibilidade diagnóstica do método de imunofenotipagem por citometria de fluxo para síndromes linfoproliferativas a partir da definição de um painel mínimo de anticorpos. MATERIAL E MÉTODOS: Participaram 47 pacientes para diagnóstico diferencial dos subtipos de síndromes linfoproliferativas por citometria de fluxo, no período de julho de 2008 a julho de 2010, atendidos na Fundação HEMOPA. RESULTADOS: A mediana de idade dos pacientes foi de 68 anos, não houve diferença estatística entre os sexos e o subtipo de síndromes linfoproliferativas mais frequente foi a leucemia linfoide crônica/linfoma linfocítico de pequenas células B. CONCLUSÃO: O método de imunofenotipagem por citometria de fluxo, ao lado da morfologia, de amostras de sangue periférico mostrou-se uma metodologia auxiliar, segura, rápida, factível e não invasiva para o diagnóstico de síndromes linfoproliferativas crônicas a partir do painel de anticorpos sugerido.

INTRODUCTION: Lymphoproliferative syndromes comprise a heterogeneous group of malignant neoplasias with different clinical behaviors, pathological factors and epidemiological characteristics, whose diagnosis may be based on lymphoid cell morphology observed in peripheral blood. OBJECTIVE: To test the diagnostic feasibility of immunophenotyping by flow cytometry for lymphoproliferative syndromes through the definition of minimal antibody panel. MATERIAL AND METHODS: During the period of July 2008 to July 2010, 47 patients from HEMOPA blood center participated in this study for differential diagnosis of lymphoproliferative syndromes subtypes by flow cytometry. RESULTS: The mean age was 68 years old. There was no statistical difference between genders, and the most frequent subtype of lymphoproliferative syndromes was chronic lymphoid leukemia/small B-cell lymphocytic lymphoma. CONCLUSION: Based on the antibody panel recommended in this investigation, the immunophenotyping method by flow cytometry associated with morphological characterization of peripheral blood samples is a reliable, rapid, feasible, and non-invasive procedure for the diagnosis of chronic lymphoproliferative syndromes.

Estudio de las aneuploidías del cromosoma 17 y la deleción del gen TP53 en neoplasias hematológicas, por la técnica del FISH-bicolor / Study of chromosome 17 aneuploidy and of TP53 gene deletion in patients with hematological neoplasias by dualcolor fluorescence in situ hybridization (FISH)

Las neoplasias hematológicas se caracterizan por presentar una amplia diversidad de alteraciones genéticas. Se analizaron 15 muestras de pacientes con diferentes tipos de neoplasias hematológicas mediante la técnica FISH, para detectar aneuploidías del cromosoma 17 y la deleción del gen TP53. En 11 de ellas se hicieron análisis cromosómicos por citogenética convencional; 6 de las 11 tenían cariotipo anormal (54,5%): se detectaron 3 translocaciones y 3 mosaicismos. El análisis de las 15 muestras mediante la técnica FISH mostró un 26,7% de aneuploidía del cromosoma 17 y un 33,3% con deleción del gen TP53. De los 6 casos con cariotipo anormal, en 2 se detectaron alteraciones por FISH. En 5 casos se detectaron con esta técnica alteraciones cromosómicas no observadas por citogenética convencional. Solo en 3 (20%) de las 15 muestras analizadas el análisis cromosómico resultó normal por citogenética convencional y FISH. En este trabajo se corrobora que la aneuploidía del cromosoma 17 y la deleción del gen TP53 tienen una baja frecuencia en las neoplasias hematológicas. Sin embargo, el valor pronóstico de estas alteraciones genéticas no está bien definido.

Hematological neoplasias are characterized by a wide spectrum of genetic alterations. We analyzed 15 specimens from patients with various types of hematological malignancies by means of the FISH technique in order to detect aneuploidy of chromosome 17 and deletion of TP53 gene. In 11 of them chromosomal analyses were also carried out using conventional cytogenetic techniques; in 6 of these 11 specimens (54.5%) abnormal karyotypes were detected, namely: 3 translocations and 3 mosaicisms. FISH results revealed that in 26.7% of the 15 specimens there was chromosome 17 aneuploidy, and that 33.3% had TP53 deletion. Out of the 6 cases with abnormal karyotypes, further alterations were detected in two by FISH. In 5 cases chromosomal abnormalities were detected by FISH but not by the conventional cytogenetic procedures. Only in 3 (20%) out of the 15 specimens the results of chromosomal analyses were normal by both the conventional cytogenetics and FISH. These results corroborate the low frequency of chromosome 17 aneuploidy and of TP53 gene deletion in hematological neoplasias. However, the prognostic value of these genetic alterations is still not well defined.