Management of chemotherapy-induced febrile neutropenia and use of granulocyte colony-stimulating factor in patients with soft tissue or bone sarcoma.

INTRODUCTION: Febrile neutropenia, an oncological complication related to myelosuppressive chemotherapy, can lead to unplanned hospitalization, morbidity, mortality, and changes in the oncological therapeutic plan. The present study aimed (1) to determine the prevalence of chemotherapy-induced febrile neutropenia requiring hospitalization and the use of granulocyte colony-stimulating factor and (2) to evaluate its consequences for the oncological treatment of patients with soft tissue or bone sarcomas. METHODS: This is a cross-sectional and retrospective study (January 2018 to December 2019) carried out in a reference oncology hospital in the Brazilian public health system. Inpatients diagnosed with chemotherapy-induced febrile neutropenia, older than the age of 18 years, and treated with granulocyte colony-stimulating factor were included in the study. RESULTS: Twenty-nine chemotherapy-induced febrile neutropenia events were identified, involving 25 patients. Among the febrile neutropenia events, 90% were grade 4, and 59% occurred during palliative chemotherapy. Among patients with febrile neutropenia, 31% had arterial hypertension or/and diabetes mellitus comorbidities, 34% had infectious skin sites, such as compression ulcers and tumor wounds, and 31% had infections with defined etiologic agents. Treatment of hospitalized patients was performed with cefepime in combinations or alone (97%) and filgrastim. The outcomes related to chemotherapy-induced febrile neutropenia were chemotherapy dose reduction (31%), chemotherapy cycle delays (21%), chemotherapy treatment suspension (17%), deaths (7%), and other associated complications (10%). Granulocyte colony-stimulating factor prophylaxis was prescribed in 72.41% of febrile neutropenia events. The frequency of febrile neutropenia concerning total chemotherapy cycles was 2.15%. CONCLUSION: Even with granulocyte colony-stimulating factor prophylaxis, an overall prevalence of 2.15% of febrile neutropenia associated with hospitalization was observed, causing negative outcomes in chemotherapy treatment of patients.

Uso do dispositivo Pegfilgrastim OBI para prevenção de neutropenia: revisão de escopo / Uso del dispositivo Pegfilgrastim OBI para prevenir la neutropenia: revisión de alcance / Pegfilgrastim OBI device use for neutropenia prevention: a scoping review

Resumo Objetivo Mapear os cuidados em saúde do dispositivo Pegfilgrastim on-body injector na prevenção de neutropenia em adultos com câncer em assistência domiciliar após quimioterapia ambulatorial. Métodos Revisão de escopo baseada na metodologia do Joanna Briggs Institute . Foram incluídos somente estudos com adultos com câncer submetidos à quimioterapia ambulatorial. A busca foi realizada nas bases de dados Cochrane, CINAHL, EMBASE, LILACS , PubMed, Scopus, LIVIVO e Web of Science, além da literatura cinzenta ProQuest, Scielo, Banco de Dados em Enfermagem, Google Scholar, Open Grey, bula do medicamento e websites . Foram esgotadas as buscas nas referências dos estudos elegidos. Todos os estudos identificados foram exportados para o gerenciador de referências EndNote para organização e remoção das duplicadas. Utilizou-se o aplicativo web Rayyan para seleção das evidências. Os estudos foram selecionados por pares e de forma independente, sendo os conflitos solucionados por um terceiro pesquisador. Resultados Foram incluídos 10 artigos cujos resultados foram subdivididos nas categorias: adesão do paciente, opinião da equipe de saúde, carga de trabalho do paciente em tratamento do câncer e uso do dispositivo na prática clínica. O dispositivo apresenta poucas falhas e foi aceito pelas equipes de saúde e pacientes na maioria dos estudos. Conclusão Os principais cuidados em saúde para o uso do dispositivo Pegfilgrastim on-body injector estão relacionados à técnica de preparo da pele onde o dispositivo será aplicado, o preparo e a administração do dispositivo. Além disso, salienta-se a importância da avaliação do conhecimento do paciente e seu familiar sobre o dispositivo, o fornecimento de todas as orientações necessárias, verbalmente e por escrito, de forma clara e objetiva, e a validação dessas informações, certificando-se que o paciente compreendeu todas elas e está seguro.

Resumen Objetivo Mapear los cuidados de la salud al utilizar el dispositivo Pegfilgrastim on-body injector para prevenir la neutropenia en adultos con cáncer en atención domiciliaria después de quimioterapia ambulatoria. Métodos Revisión de alcance basada en la metodología del Joanna Briggs Institute . Se incluyeron solamente estudios con adultos con cáncer sometidos a quimioterapia ambulatoria. La búsqueda se realizó en las bases de datos Cochrane, CINAHL, EMBASE, LILACS , PubMed, Scopus, LIVIVO y Web of Science, además de la literatura gris ProQuest, Scielo, Banco de Datos de Enfermería, Google Scholar, Open Grey, prospecto del medicamento y sitios web. Se concluyeron las búsquedas en las referencias de los estudios seleccionados. Todos los estudios identificados se exportaron al programa de gestión de referencias EndNote para organizarlas y remover las duplicadas. Se utilizó la aplicación web Rayyan para seleccionar las evidencias. Se seleccionaron los estudios por pares y de forma independiente, y los conflictos se solucionaron mediante un tercer investigador. Resultados Se incluyeron diez artículos cuyos resultados fueron subdivididos en las siguientes categorías: adhesión del paciente, opinión del equipo de salud, carga de trabajo del paciente en tratamiento de cáncer y uso del dispositivo en la práctica clínica. El dispositivo presenta pocas fallas y fue aceptado por los equipos de salud y por los pacientes en la mayoría de los estudios. Conclusión Los principales cuidados de la salud para el uso del dispositivo Pegfilgrastim on-body injector se relacionan con la técnica de preparación de la piel donde se aplicará el dispositivo, la preparación y la administración del dispositivo. Además, se destaca la importancia de la evaluación de conocimientos del paciente y su familiar sobre el dispositivo, la entrega de todas las instrucciones necesarias, verbalmente y por escrito, de forma clara y objetiva, la validación de la información y la verificación de que el paciente haya comprendido todo y esté seguro.

Abstract Objective To map the health care of Pegfilgrastim On-body Injector in neutropenia prevention in adults with cancer in home care after outpatient chemotherapy. Methods This is a scoping review based on the JBI methodology. Only studies with adults with cancer undergoing outpatient chemotherapy were included. The search was carried out in the Cochrane, CINAHL, EMBASE, LILACS, PubMed, Scopus, LIVIVO and Web of Science databases, in addition to gray literature ProQuest, SciELO, Database in Nursing, Google Scholar, Open Grey, drug leaflet and websites. The searches in the references of selected studies were exhausted. All identified studies were exported to the EndNote reference manager for organization and removal of duplicates. The Rayyan web application was used for evidence selection. The studies were selected by pairs independently, with conflicts resolved by a third researcher. Results A total of 10 articles were included, whose results were subdivided into categories: patient compliance, health team opinion, patient workload in cancer treatment and device use in clinical practice. The device has few flaws and was accepted by health care teams and patients in most studies. Conclusion The main health care for Pegfilgrastim On-body Injector use is related to the skin preparation technique where the device will be applied, in addition to device preparation and administration. Moreover, the importance of assessing the knowledge of patients and their family about the device is highlighted, providing all the necessary guidelines, verbally and in writing, clearly and objectively, and validating this information, making sure that patients have understood all of them and are safe.

Filgrastim (r-met-hu G-CSF) enhances the efficiency of spermatogenesis in prepubertal Bos indicus bulls.

This study aimed to test the effects of the drug r-met-hu-G-CSF (filgrastim) on spermatogenic efficiency in prepubertal Brahman bulls. Twelve intact, healthy prepubertal bulls were administered 0, 1 (LD = low dose) or 4 (HD = high dose) µg/Kg r-met-hu-G-CSF (daily for 4 days), and haematological analysis was performed. Bulls were castrated (D0 or D60). BW (body weight) and SC (scrotal circumference) were recorded. Testis weight and volume were taken at castration with samples for testis histology and stereology: germ cell types, spermatids count and DSP (daily sperm production per gram)/g of testicular parenchyma. Testicular weight, volume, BW, SC and gonadosomatic index (GSI) were NS (LD-HD; p > .05). At D0 (age 11 months), the most advanced germ cell types (maGCt) ranged from intermediate spermatogonia to pachytene spermatocytes. After 2 months, control animals had round spermatids as maGCt, LD animals 75% round spermatids and 25% elongated spermatids, and HD animals round spermatids. Spermatids/testis were higher in LD (1.23 ± 0.2 millions) than in controls (0.65 ± 0.1 millions, p < .05). Spermatogenic efficiency (DSP/g) was higher in LD (5.4 ± 0.4 million) than in controls (3.2 ± 0.2 million, p < .01). In conclusion, r-met-hu-G-CSF raises spermatogenic efficiency in prepubertal Brahman bulls.

Manejo em longo prazo de glicogenose tipo 1b: experiência de um centro terciário brasileiro / Long term management of glycogen storage disease type 1b: a brazilian tertiary center experience

ABSTRACT BACKGROUND Glycogen storage disease (GSD) type 1b is a multisystemic disease in which immune and infectious complications are present, in addition to the well-known metabolic manifestations of GSD. Treatment with granulocyte-colony stimulating factor (G-CSF) is often indicated in the management of neutropenia and inflammatory bowel disease. OBJECTIVE To report on the demographics, genotype, clinical presentation, management, and complications of pediatric patients with glycogen storage disease type 1b (GSD 1b), with special attention to immune-related complications. METHODS Retrospective case series of seven patients with GSD 1b diagnosed and followed at a tertiary university hospital in Brazil, from July/2000 until July/2016. RESULTS Mean age at referral was fourteen months. Diagnosis of GSD 1b was based on clinical and laboratory findings and supported by genetic studies in five cases. All patients presented suffered from neutropenia, managed with G-CSF - specifically Filgrastim. Hospitalizations for infections were frequent. Two patients developed inflammatory bowel disease. Six patients remained alive, one died at age 14 years and 9 months. The mean age at the end of the follow-up was 11.5 years. Compliance to treatment was suboptimal: poor compliance to medications, starch and dietetic management of GSD were documented, and outpatient appointments were frequently missed. CONCLUSION Managing GSD 1b is challenging not only for the chronic and multisystemic nature of this disease, but also for the additional demands related dietary restrictions, use of multiple medications and the need for frequent follow-up visits; furthermore in Brazil, the difficulties are increased in a scenario where we frequently care for patients with unfavorable socioeconomic status and with irregular supply of medications in the public health system.

RESUMO CONTEXTO Glicogenose (GSD) tipo 1b é uma doença multissistêmica em que complicações imunológicas e infecciosas estão presentes, além das manifestações metabólicas bem conhecidas da GSD. O tratamento com fator estimulador de colônias de granulócitos (G-CSF) é frequentemente indicado no tratamento da neutropenia e doença inflamatória intestinal. OBJETIVO Relatar sobre a dados demográficos, genótipo, apresentação clínica, manejo e complicações de pacientes pediátricos com GSD tipo 1b (GSD 1b), com atenção especial às complicações relacionadas ao sistema imunológico. MÉTODOS Série de casos retrospectiva de sete pacientes com GSD 1b diagnosticados e acompanhados em um hospital universitário terciário no Brasil, de julho/2000 a julho/2016. RESULTADOS A idade média no encaminhamento foi de 14 meses. O diagnóstico de GSD 1b foi baseado em achados clínicos e laboratoriais e apoiado por estudos genéticos em cinco casos. Todos os pacientes apresentaram neutropenia, tratada com G-CSF - especificamente Filgrastim. As hospitalizações por infecções foram frequentes. Dois pacientes desenvolveram doença inflamatória intestinal. Seis pacientes permanecem vivos, um morreu aos 14 anos e 9 meses de idade. A média de idade ao final do acompanhamento foi de 11,5 anos. A adesão ao tratamento foi sub-ótima: má adesão aos medicamentos, amido e manejo dietético de GSD foram documentados, e consultas ambulatoriais foram frequentemente perdidas. CONCLUSÃO O manejo da GSD 1b é um desafio, não apenas pela natureza crônica e multissistêmica desta doença, mas também pelas demandas adicionais relacionadas a restrições dietéticas, uso de múltiplos medicamentos e a necessidade de consultas de acompanhamento frequentes; no Brasil, isso ainda é dificultado em um cenário em que frequentemente atendemos pacientes com situação socioeconômica desfavorável e com oferta irregular de medicamentos no sistema público de saúde.

Filgrastim-induced rhabdomyolysis in a healthy stem cells donor.

INTRODUCTION: Mobilization of peripheral blood progenitor cells with the use of granulocyte-colony stimulating factors is a mainstay in every protocol for allogenic stem cell transplants. Despite being considered safe, there are multiple adverse effects for this procedure some of which can be severe and bring serious complications to otherwise healthy donors. CASE REPORT: An otherwise healthy 17-year-old patient who underwent progenitor cell mobilization with filgrastim and developed rhabdomyolysis and acute kidney injury.Management and outcome: The urine analysis and kidney ultrasound failed to reveal abnormalities in the kidneys or collector system. We began reanimation with crystalloid solutions for 5 days with normalization of liver and muscle enzymes as well as a complete resolution of the acute kidney injury. DISCUSSION: We present the case of a potentially serious adverse drug reaction during mobilization of peripheral blood progenitor cells with filgrastim. Physicians need to be aware of every possible complication associated with the use of these agents in order to establish a good prognosis via an accurate diagnosis and a timely treatment.

Efficacy of three filgrastim-intended copies for hematopoietic stem cell mobilization in healthy adult and pediatric donors in Mexico.

INTRODUCTION: The use of filgrastim biosimilars for healthy adult and pediatric donor mobilization in hematopoietic stem cell transplantation has been met with increased safety and efficacy concerns in contrast to generic small molecule drugs. In Mexico, several filgrastim-intended copies (FIC) have been available and marketed since 2001, while no clinical comparability studies to evaluate their use in this setting have been published and thus are not considered to be true biosimilars. In this study, we report our experience using three different FIC products currently available (Filatil, Dextrifyl, and Biofilgran). METHODS: We retrospectively evaluated 118 related donors of all ages who received any brand 5 µg/kg subcutaneously twice daily for 4 days and were harvested in a single apheresis system on day 5. RESULTS: Donors had a median age of 38 years (range, 1-69). A successful harvest defined as ≥2 × 106 CD34+ cells/kg of recipient weight was achieved in 95.8% of cases, with a median CD34+ cell dose of 9.4 × 106 /kg (range 1-42.8). A single apheresis session was performed in 89.8% of cases. No significant difference in cell yield between each brand was observed. All pediatric donors had a successful harvest with similar results to adult donors. No immediate severe adverse effects were documented in any case. CONCLUSIONS: In conclusion, three FICs available in Mexico were efficacious and without immediate severe adverse effects, resulting in significant cost savings. Evaluation of immunogenicity and establishment of a pharmacovigilance program with the use of FICs is warranted.

Real-world safety experience of tevagrastim/ratiograstim/biograstim and tbo-filgrastim, short-acting recombinant human granulocyte colony-stimulating factors.

PURPOSE: Recombinant granulocyte colony-stimulating factors (rG-CSFs), such as filgrastim, are administered to prevent complications in patients receiving chemotherapy. In Europe, a biosimilar to filgrastim, tevagrastim/ratiograstim/biograstim, was approved in 2008. In the USA, the same product was approved as tbo-filgrastim under a 351(a) biologic license application in 2012 with the brand name Granix®. Postmarket surveillance remains a priority for monitoring the safety of biologics and biosimilars to identify rare and immunogenicity-related events. We report the global and US pharmacovigilance data for tevagrastim/ratiograstim/biograstim and tbo-filgrastim, respectively. METHODS: Cumulative exposure and adverse event data from initial approval in Europe to December 31, 2016, were collected globally from spontaneous reports submitted by healthcare professionals and consumers, scientific literature, competent authorities, and solicited case reports from non-interventional studies. A separate search was conducted on the global data set to identify reports originating from the USA and Puerto Rico to describe the US experience. RESULTS: Overall, the global safety profile of tevagrastim/ratiograstim/biograstim in the postmarket, real-world setting was comparable to clinical trial experience. Postmarket safety experience of tbo-filgrastim in the USA was consistent with global data. The most common SAEs were febrile neutropenia and decreased white blood cell count. The most common non-serious event was bone pain. There was no evidence of immunogenicity. CONCLUSIONS: This pharmacovigilance analysis indicates that postmarket experience of tevagrastim/ratiograstim/biograstim and tbo-filgrastim is consistent with clinical trials. Adverse reactions associated with the originator rG-CSF (capillary leak syndrome and glomerulonephritis) have not been observed with tevagrastim/ratiograstim/biograstim or tbo-filgrastim during the postmarket period.

Avaliação técnico-regulatória dos requisitos de qualidade para registro de medicamentos biológicos e biossimilares humanos: perspectivas e desafios no Brasil / Technical and regulatory evaluation of quality requirements for the registration of human biological and biosimilar drugs: perspectives and challenges in Brazil

Medicamentos biológicos são obtidos a partir de fluidos biológicos ou tecidos de origem animal por procedimentos biotecnológicos e, a partir do vencimento das suas patentes, surge a possibilidade da produção de suas cópias, os chamados biossimilares. Este tema, além de polêmico, por ainda apresentar divergências de entendimento da classe científica, também engloba 4 das 5 classes terapêuticas de medicamentos mais vendidas, e apresenta evolução crescente no mercado farmacêutico. Com o aumento da demanda, cresce o interesse na produção de medicamentos biológicos de alta qualidade, com a mesma eficácia, porém a preços mais baixos. Dessa forma, é possível entender a responsabilidade das regulamentações, principalmente no que diz respeito aos biossimilares, a fim de que eles respeitem os requisitos mínimos necessários para serem comparáveis ao seu medicamento biológico novo. Assim, este trabalho teve como objetivo avaliar questões técnico-regulatórias e os requisitos de qualidade para registro de medicamentos biológicos e biossimilares humanos frente a diferentes Autoridades Sanitárias mundiais. A análise foi baseada em três moléculas biológicas, sendo a clássica heparina e moléculas novas, filgrastim e infliximabe. Foi constatado que na teoria, a legislação brasileira é baseada em regulamentos internacionais, especialmente da Federal and Drug Administration (FDA) e European Medicines Agency (EMA), e que na prática, o Brasil tem se mostrado mais conservador na extrapolação de indicação e na aprovação dos biossimilares. Ainda, foi possível notar que independente do país, as Farmacopeias ainda necessitam de aprimoramento com relação a este tema, pois em sua maioria, não existe padronização dos parâmetros e testes a serem realizados. Pesquisa demonstrou que o conhecimento sobre biossimilares ainda não está consolidado entre profissionais médicos e que, portanto, há necessidade de programas para esclarecimentos, com a finalidade de estimular seu uso, quando possível e com custos mais interessantes

Biological drugs are obtained from biological fluids or animals tissues by biotechnological procedures and, from the expiration of their patents, the possibility of producing their "copies", the so-called biosimilars, arises. In addition to being a controversial subject, as it still presents divergences of understanding by the scientific class, it also encompasses 4 of the 5 therapeutic classes of best-selling drugs, and it presents an increasing evolution in the pharmaceutical market. As demand increases, interest in the production of high-quality biological drugs with the same effectiveness, but at lower prices, also increases. In this way, it is possible to understand the responsibility of regulations, especially with regard to biosimilars, so that they comply with the minimum requirements needed to be comparable to their reference biological medicine. Thus, the objective of this project was to evaluate technical and regulatory topics, as well as quality requirements for the registration of human biological and biosimilar medicines under the perspective of different Health Authorities around the world. The analysis was based on three biological molecules, being the classic heparin and new molecules, filgrastim and infliximab. It was found that in theory, Brazilian regulation is based on international regulations, especially the Federal and Drug Administration (FDA) and the European Medicines Agency (EMA), and that in practice, Brazil has been more conservative in the extrapolation of indication and approval of biosimilars. Also, it was possible to note that, regardless the country, Pharmacopoeias still need to be improved for this topic, since in general, there is no standardization of the parameters and tests to be performed. Research showed that the knowledge about biosimilars is not yet consolidated among doctors and that, therefore, there is a need for clarification programs, with the purpose of stimulating their use, when possible and at lower costs

Cost-effectiveness and budgetary impact of lipegfilgrastim for the reduction of chemotherapy-induced neutropenia in Brazil / Custo-benefício e impacto orçamentário do lipegfilgrastim para a redução de neutropenia induzida por quimioterapia no Brasil

Background: Granulocyte-colony stimulating factors (G-CSFs) reduce the risk of chemotherapy-induced neutropenia. Lipegfilgrastim is a long-acting, once-per-cycle G-CSF, while Brazil's standard of care is short-acting filgrastim. A cost-effectiveness and budget impact analysis of lipegfilgrastim was conducted with filgrastim and once-per-cycle pegfilgrastim for adults at risk of neutropenia in Brazil. Methods: The decision model used national and clinical data to evaluate the costs and outcomes of each treatment. Costs included drug and medical expenses, outpatient and inpatient neutropenia treatments, and adverse events. Health outcomes included incidence of neutropenia-related events. For the budget impact analysis, health outcomes and costs for the pre/post-lipegfilgrastim scenarios were combined to identify expenditure with lipegfilgrastim's introduction. Results: Total cost per patient during a course of four chemotherapy cycles was estimated at R$12,920 for lipegfilgrastim, R$15,168 for filgrastim, and R$13,232 for pegfilgrastim. Based on better outcomes and lower total costs with lipegfilgrastim compared with filgrastim as well as pegfilgrastim, lipegfilgrastim was the dominant treatment strategy over both filgrastim and pegfilgrastim during the duration of chemotherapy treatment. Over 5 years, the uptake of lipegfilgrastim led to savings of R$61,532,403 in overall medical costs. Neutropenic events decreased by 17,141 and deaths linked to febrile neutropenia decreased by 239. Conclusion: Due to better outcomes and lower overall cost, lipegfilgrastim was a cost-saving strategy compared with filgrastim and pegfilgrastim in the Brazilian healthcare system. Furthermore, the budget impact analysis estimated a reduction in overall medical costs and improved health outcomes over 5 years following the introduction of lipegfilgrastim.

Introdução: Fatores estimuladores de colônias de granulócitos (G-CSFs) reduzem risco de neutropenia induzida por quimioterapia. Lipegfilgrastim é um G-CSF de longa ação, de "um por ciclo", enquanto o padrão de cuidado no Brasil é filgrastim de curta ação. Realizou-se uma análise de custo/ benefício e impacto orçamentário (IO) no Brasil do lipegfilgrastim um por ciclo com filgrastim e pegfilgrastim para adultos sob risco de neutropenia. Métodos: O modelo de decisão usou dados nacionais e clínicos para avaliar resultados e custos dos tratamentos que incluíam medicamentos, médicos, tratamentos ambulatoriais e hospitalares para a neutropenia, e eventos adversos. Resultados de saúde incluíam a incidência de eventos relacionados à neutropenia. Para a análise do IO, os custos e resultados de antes/depois do lipegfilgrastim foram combinados para identificar gastos com o lipegfilgrastim. Resultados: O custo total por paciente em quatro ciclos foi estimado em R$ 12.920 para lipegfilgrastim, R$ 15.168 para filgrastim e R$ 13.232 para pegfilgrastim. Com base em melhores resultados e custos totais menores, o lipegfilgrastim, comparado ao filgrastim e ao pegfilgrastim, representou a estratégia de tratamento predominante. Em 5 anos, o lipegfilgrastim gerou uma economia de R$ 61.532.403 em custos médicos gerais. Houve 17.141 menos eventos neutropênicos e as mortes relacionadas à neutropenia febril reduziram em 239. Conclusão: Devido a melhores resultados e menores custos, lipegfilgrastim, comparado ao filgrastim e ao pegfilgrastim, foi uma estratégia econômica no sistema brasileiro. A análise de IO estimou uma redução nos custos médicos e melhorou os resultados em 5 anos após a introdução do lipegfilgrastim.

Impacto de la medicina regenerativa en angiología. Experiencia cubana / Impact of the regenerative medicine in Angiology. Cuban experience

Introducción: La medicina regenerativa se apoya fundamentalmente en la terapia celular, en la administración de factores bioactivos, en la ingeniería de tejidos y en la terapia génica, integra todos estos procederes destinados a la promoción de la regeneración celular.Objetivo: Comunicar los principales resultados de la aplicación de la medicina regenerativa en Cuba en la especialidad de angiología.Métodos: Para la implantación celular se emplearon células mononucleares de la médula ósea y también las movilizadas con Filgrastim a la sangre periférica. Las plaquetas se usaron en forma de plasma rico en plaquetas o de lisado plaquetario. Se incluyeron los pacientes con diferentes enfermedades vasculares atendidos en instituciones del país en el período 2004-2015.Resultados: Con la terapia celular se obtuvo resultados favorables en pacientes con isquemia crítica de miembros inferiores, claudicación intermitente, tromboangeítis obliterante, pie diabético, síndrome posflebítico y linfedema de miembros inferiores. Con el uso de las plaquetas se obtuvieron resultados prometedores en pacientes claudicantes, con pie diabético y úlceras posflebíticas.Conclusiones: El balance realizado al finalizar el 2015 demuestra que el uso de la medicina regenerativa ha sido introducida en 14 de las 15 provincias cubanas. Se han beneficiados con la terapia celular 9 124 pacientes, de ellos 3 741 (41 por ciento) de la especialidad de angiología. Esta terapia resulta de menor costo que los procedimientos convencionales empleados en el tratamiento de las enfermedades vasculares periféricas; evita la amputación y el impacto social que esto representa se cuenta entre sus resultados más importantes(AU)

Introduction: Regenerative medicine is fundamentally based on cell therapy, administration of bioactive factors, tissue engineering and gene therapy and integrates all these procedures intended to promote cell regeneration.Objective: To present the main results of application of regenerative medicine in angiology in our country.Method: For cell implantation, mononuclear cells from the bone marrow and also those released with Filgrastim into the peripheral blood were used. Platelets were then used as platelet-rich plasma or platelet lysate. Patients with different vascular disorders, who had been treated in the 2004-2015 period in various domestic institutions, were included in this study.Results: The cell therapy yielded positive results in patients with critical lower limb ischemia, intermittent claudication, thromboangiitis obliterans, diabetic foot, postphlebitic syndrome, and lower limb lymphedema. The use of platelets showed promising results in patients with intermittent claudication, diabetic foot, and postphlebitic ulcers.Conclusions: The assessment made at the end of 2015 shows that regenerative medicine is implemented in 14 of the 15 Cuban provinces. A total number of 9 124 patients, 3 741 (41 percent) of whom are treated by the angiology specialty have benefited from cell therapy. This type of therapy is less costly than the conventional methods used in the treatment of peripheral vascular diseases, and avoidance of amputation and its social impact are the most significant outcomes of this therapy(AU)

Impacto de la medicina regenerativa en angiología. Experiencia cubana / Impact of the regenerative medicine in Angiology. Cuban experience

Introducción: La medicina regenerativa se apoya fundamentalmente en la terapia celular, en la administración de factores bioactivos, en la ingeniería de tejidos y en la terapia génica, integra todos estos procederes destinados a la promoción de la regeneración celular. Objetivo: Comunicar los principales resultados de la aplicación de la medicina regenerativa en Cuba en la especialidad de angiología. Métodos: Para la implantación celular se emplearon células mononucleares de la médula ósea y también las movilizadas con Filgrastim a la sangre periférica. Las plaquetas se usaron en forma de plasma rico en plaquetas o de lisado plaquetario. Se incluyeron los pacientes con diferentes enfermedades vasculares atendidos en instituciones del país en el período 2004-2015. Resultados: Con la terapia celular se obtuvo resultados favorables en pacientes con isquemia crítica de miembros inferiores, claudicación intermitente, tromboangeítis obliterante, pie diabético, síndrome posflebítico y linfedema de miembros inferiores. Con el uso de las plaquetas se obtuvieron resultados prometedores en pacientes claudicantes, con pie diabético y úlceras posflebíticas. Conclusiones: El balance realizado al finalizar el 2015 demuestra que el uso de la medicina regenerativa ha sido introducida en 14 de las 15 provincias cubanas. Se han beneficiados con la terapia celular 9 124 pacientes, de ellos 3 741 (41 por ciento) de la especialidad de angiología. Esta terapia resulta de menor costo que los procedimientos convencionales empleados en el tratamiento de las enfermedades vasculares periféricas; evita la amputación y el impacto social que esto representa se cuenta entre sus resultados más importantes

Introduction: Regenerative medicine is fundamentally based on cell therapy, administration of bioactive factors, tissue engineering and gene therapy and integrates all these procedures intended to promote cell regeneration. Objective: To present the main results of application of regenerative medicine in angiology in our country. Method: For cell implantation, mononuclear cells from the bone marrow and also those released with Filgrastim into the peripheral blood were used. Platelets were then used as platelet-rich plasma or platelet lysate. Patients with different vascular disorders, who had been treated in the 2004-2015 period in various domestic institutions, were included in this study. Results: The cell therapy yielded positive results in patients with critical lower limb ischemia, intermittent claudication, thromboangiitis obliterans, diabetic foot, postphlebitic syndrome, and lower limb lymphedema. The use of platelets showed promising results in patients with intermittent claudication, diabetic foot, and postphlebitic ulcers. Conclusions: The assessment made at the end of 2015 shows that regenerative medicine is implemented in 14 of the 15 Cuban provinces. A total number of 9 124 patients, 3 741 (41 percent) of whom are treated by the angiology specialty have benefited from cell therapy. This type of therapy is less costly than the conventional methods used in the treatment of peripheral vascular diseases, and avoidance of amputation and its social impact are the most significant outcomes of this therapy(AU)

¿Es realmente útil el tratamiento con la terapia celular regenerativa? / Is it really useful the treatment with regenerative cell therapy?

La Medicina Regenerativa se apoya fundamentalmente en la terapia celular, en la administración de factores bioactivos, en la ingeniería de tejidos y en la terapia génica. Según su estado evolutivo, las células madre pueden clasificarse en embrionarias y adultas. Recientemente se obtuvieron células con características embrionarias mediante la reprogramación de células adultas que se llamaron células madre pluripotentes inducidas. Se han obtenido importantes avances con la terapia con células madre adultas que tienen notables ventajas sobre las embrionarias, pues su manipulación resulta más simple y se pueden obtener del propio individuo que va a ser tratado. Los resultados obtenidos en Cuba evidencian los beneficios que la terapia celular puede aportar en pacientes sin otras opciones terapéuticas y sobre todo bajo un estricto control científico(AU)

Regenerative Medicine is fundamentally based on cell therapy, administration of bioactive factors, tissue engineering and gene therapy. According to their evolutionary state, stem cells can be classified into embryonics and adults. Recently were obtained cells with embryonic characteristics by reprogramming adult cells and have been called induced pluripotent stem cells. Already have been made significant progress in cell therapy using adult stem cells, which have significant advantages over embryonic cells, because its handling is simpler, and can be obtained from the own individual to be treated. The results obtained in Cuba show the benefits that cell therapy can bring to patients with no other therapeutic options and especially under strict scientific control(AU)

Costo- Efectividad Del Uso Profiláctico Del Factor Estimulante De Colonias De Granulocitos En Adultos Con Leucemia Linfoblástica Aguda en Colombia.

OBJECTIVE: To assess the cost-effectiveness of prophylactic administration of Granulocyte Colony-Stimulating Factor (G-CSF) compared with no use of it, during the induction phase of chemotherapy in Adults with Acute Lymphoblastic Leukemia (ALL) in Colombia. METHODS: A decision tree with a time horizon of 30 days was built under colombian health system perspective including only direct costs. The costs of procedures and medications were taken from official sources and an institution of national reference of oncology services. The safety and effectiveness data were taken from the literature and two Colombian cohorts with patients older than 15 years. The unit of outcome was the proportion of deaths avoided. RESULTS: Base-case results on a clinical trial indicate that using factor is a dominant strategy. The variable that most impacted the outcome was the incidence of febrile neutropenia. Considering a threshold of $22.228 USD in 80% of cases using factor was cost effective. However, the use of factor is not cost-effective for the country for incidences of febrile neutropenia > 48%. It was not possible to establish cost-effectiveness of pegfilgrastim because no information was found. CONCLUSION: As per Colombian data, the use of prophylactic factor under chemotherapeutic induction in adults with ALL, turns out to be not cost effective. The difference in the results suggests the need of a careful extrapolation of information from clinical trials (ideal world) for developing economic evaluations in Colombia.

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¯).

Evaluación de efectividad y seguridad comparativas del filgrastim para la prevención de neutropenia febril, en pacientes con cáncer sometidos a quimioterapia citotóxica / Comparative effectiveness and safety assessment of filgrastim for the prevention of febrile neutropenia in cancer patients undergoing cytotoxic chemotherapy

Introducción: la neutropenia febril es una complicación frecuente en pacientes con cáncer sometidos a quimioterapia citotóxica. Entre las opciones para prevenir esta complicación está el filgrastim. Esta evaluación de tecnología se desarrolló para informar la toma de decisiones en el marco de la actualización integral del Plan Obligatorio de Salud para Colombia. Objetivo: examinar la efectividad y seguridad comparativas del filgrastim para la prevención de neutropenia febril, en pacientes con cáncer sometidos a quimioterapia citotóxica. Metodología: se realizó una búsqueda sistemática en MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects y LILACS. La tamización de referencias se realizó por dos revisores de forma independiente y la selección de estudios fue hecha por un revisor, aplicando los criterios de elegibilidad predefinidos en el protocolo de la evaluación. La calidad de las revisiones sistemáticas se valoró con la herramienta AMSTAR. Se realizó una síntesis narrativa y meta-analítica de las estimaciones del efecto para las comparaciones y desenlaces de interés. Resultados: los hallazgos de efectividad y seguridad de la presente evaluación se basan en tres revisiones sistemáticas de calidad media, tres meta-análisis de comparaciones directas (dos publicados y uno de novo) y ocho ensayos clínicos cabeza a cabeza, siete de ellos aleatorizados, incluyendo dos estudios de no inferioridad, para un total aproximado de 1072 pacientes. Se identificó evidencia de los efectos del filgrastim comparado con pegfilgrastim para una variedad de desenlaces incluyendo, neutropenia febril, hospitalización asociada, mortalidad, retraso en la quimioterapia, eventos adversos globales, serios y específicos. La evidencia disponible corresponde a adultos con cáncer de mama, linfoma no Hodgkin y enfermedad de Hodgkin, y población pediátrica con sarcomas. También se presentan los eventos adversos reportados en la etapa post-clínica con el uso del filgrastim. Conclusiones: la evidencia identificada en esta evaluación de tecnología, muestra efectos mixtos en la efectividad y seguridad del filgrastim para la prevención de neutropenia febril, en pacientes con cáncer sometidos a quimioterapia citotóxica: los resultados de efectividad indican que este medicamento puede ser similar o menos efectivo frente a su comparador y para algunos desenlaces existe incertidumbre. Respecto a la seguridad comparada del filgrastim, esta puede ser similar o incierta. A juicio de los expertos clínicos, el balance entre los beneficios y riesgos no favorece al filgrastim ni a su comparador.(AU)

Mobilization of hematopoietic progenitor cells with granulocyte colony stimulating factors for autologous transplant in hematologic malignancies: a single center experience

BACKGROUND: In 2006 the Hematology Service of Hospital Maciel published its experience with peripheral blood progenitor cell harvesting for autologous stem cell transplantation using Filgen JP (Clausen Filgrastim). After mobilization with a mean filgrastim dose of 78 mcg/Kg, 4.7 x 10(6) CD34+ cells/Kg were obtained by apheresis. Age above 50, multiple myeloma as underlying disease and a malignancy that was not in remission were identified as frequent characteristics among patients showing complex mobilization. OBJECTIVE: The aim of this study was to compare stem cell mobilization using different brands of filgrastim. METHODS: One hundred and fifty-seven mobilizations performed between 1997 and 2006 were analyzed. This retrospective analysis comparative two groups of patients: those mobilized with different brands of filgrastim (Group A) and those who received Filgen JP (Clausen Filgrastim) as mobilizing agent (Group B). A cluster analysis technique was used to identify four clusters of individuals with different behaviors differentiated by age, total dose of filgrastim required, number of apheresis and harvested CD34+ cells. RESULTS: The mean total dose of filgrastim administered was 105 mcg/Kg, the median number of apheresis was 2 procedures and the mean number of harvested stem cells was 4.98 x 10(6) CD34+ cells/Kg. No significant differences were observed between Groups A and B regarding the number of apheresis, harvested CD34+ cells and number of mobilization failures, however the total dose of filgrastim was significantly lower in Group B. CONCLUSIONS: Among other factors, the origin of the cytokine used as mobilizing agent is an element to be considered when evaluating CD34+ cell mobilization results.

Mobilization of hematopoietic progenitor cells with granulocyte colony stimulating factors for autologous transplant in hematologic malignancies: a single center experience.

BACKGROUND: In 2006 the Hematology Service of Hospital Maciel published its experience with peripheral blood progenitor cell harvesting for autologous stem cell transplantation using Filgen JP (Clausen Filgrastim). After mobilization with a mean filgrastim dose of 78 mcg/Kg, 4.7 x 10(6) CD34(+) cells/Kg were obtained by apheresis. Age above 50, multiple myeloma as underlying disease and a malignancy that was not in remission were identified as frequent characteristics among patients showing complex mobilization. OBJECTIVE: The aim of this study was to compare stem cell mobilization using different brands of filgrastim. METHODS: One hundred and fifty-seven mobilizations performed between 1997 and 2006 were analyzed. This retrospective analysis comparative two groups of patients: those mobilized with different brands of filgrastim (Group A) and those who received Filgen JP (Clausen Filgrastim) as mobilizing agent (Group B). A cluster analysis technique was used to identify four clusters of individuals with different behaviors differentiated by age, total dose of filgrastim required, number of apheresis and harvested CD34(+) cells. RESULTS: The mean total dose of filgrastim administered was 105 mcg/Kg, the median number of apheresis was 2 procedures and the mean number of harvested stem cells was 4.98 x 10(6) CD34(+) cells/Kg. No significant differences were observed between Groups A and B regarding the number of apheresis, harvested CD34(+) cells and number of mobilization failures, however the total dose of filgrastim was significantly lower in Group B. CONCLUSIONS: Among other factors, the origin of the cytokine used as mobilizing agent is an element to be considered when evaluating CD34(+) cell mobilization results.

Efectos del uso del factor estimulante de colonias granulocíticas en la obtención de células madre en un grupo de pacientes con enfermedad arterial oclusiva crónica / Effects of the use of granulocyte colony stimulating factor for obtaining stem cells in a group of patients with chronic occlusive arterial disease

Es importante evaluar el perfil del uso del factor estimulante de colonias granulocíticas (fec-g) en pacientes con enfermedad arterial oclusiva crónica (eaoc), mediante el análisis de aspectos como eficacia y seguridad. Se examinaron los datos obtenidos de la cohorte de pacientes con eaoc que asistían regularmente a la clínica de Cirugía Vascular del Hospital Militar Central en Bogotá. El protocolo de movilización de células CD34+ hacia sangre periférica consistió en el uso de FEC-Grh a dosis de 600 mg/día por vía subcutánea (Filgrastim fec-g 300 mg Roche®), repartido en dos dosis diarias, en forma continua durante cinco días. Al realizar la comparación de valores a partir de hemogramas realizados antes y después de la movilización, se demostró incremento significativo en el número de leucocitos así como en la proporción de neutrófilos y basófilos; mientras que las proporciones de monocitos, eosinófilos y linfocitos disminuyeron significativamente. Con respecto al comportamiento de las células CD34+, no se muestra una diferencia significativa en el comportamiento del CD34+ con la edad, así como tampoco con el índice de masa corporal (imc). En lo relacionado con el peso y los niveles de CD34+, se observó que los pacientes que lograron una buena respuesta tenían un peso de 59,7 kg, mientras que los pacientes con regular respuesta, 68,1 kg.

The analyzed aspects such as efficacy and safety are important in the use of Granulocyte Colony Stimulating Factor in patients with chronic occlusive arterial disease were analyzed data from the cohort of patients with eaoc that regularly attended the Clinic for Vascular Surgery of the Hospital Militar Central in Bogotá. The protocol for CD34+ cell mobilization into peripheral blood involved the use of FEC-Grh at a dose of 600 mg/day administered subcutaneously (Filgrastim g-csf 300 mg Roche®) divided into two daily doses, continuously for five days. By comparing the values from blood counts performed before and after mobilization showed increased significant number of leukocytes as well as proportion of neutrophils and basophiles, whereas proportions of monocytes, eosinophils and lymphocytes decreased significantly. About the CD34+ cell behavior, it’s not shown significant difference between the behaviors of CD34+ with age, neither the imc. The analyzed done on the weight and CD34+ levels was observed that patients achieved a good response with a weight of 59.7 kg while 68.1 kg patients with regular response.