La neutropenia: Una revisión narrativa / Neutropenia: A narrative review

Introducción: La Neutropenia constituye una de las complicaciones más comunes en pacientes que reciben tratamiento sistémico con quimioterapia, siendo esta una población heterogénea; por lo tanto su presentación clínica es inespecífica, pudiendo presentarse de manera asintomática o inclusive evidenciar cuadros muy severos con signos de sepsis grave. Ante lo referido, en la actualidad los grupos de trabajo requieren determinar de manera consistente los diferentes factores de riesgo que contribuyen a la presentación de neutropenia, con el objetivo de estratificar de manera óptima al paciente y así disminuir complicaciones. Puntos importantes: Este trabajo se enfatiza en analizar los factores de riesgo; tanto del paciente, la enfermedad y el tratamiento; de acuerdo a los sistemas de estratificación como MASCC, CISNE. Además se evaluaron los fundamentos clínicos y microbiológicos para categorizar al paciente e incluir medidas de soporte profiláctico a los grupos con mayor fragilidad, disminuyendo el alto riesgo de complicaciones severas. Conclusión: La neutropenia es un evento adverso indeseable en el manejo del tratamiento oncohematológico. Los sistemas de estratificación de riesgos MASCC y CISNE son herramientas útiles para seleccionar pacientes de bajo riesgo. Sin embargo, otros factores, como el tipo de tumor y el tipo de infección, pueden influir en la estratificación. Por lo tanto, es importante manejar a cada paciente de forma individualizada.El inicio de la profilaxis antimicrobiana y el uso de FECG pueden ayudar a reducir la morbimortalidad.

Introduction: Neutropenia is one of the most common complications in patients receiving systemic treatment with chemotherapy; this is a heterogeneous population; therefore, its clinical presentation is nonspecific, presenting asymptomatically or even showing very severe symptoms with signs of severe sepsis. Given those above, currently, the working groups need to consistently determine the different risk factors contributing to the presentation of neutropenia to stratify the patient and thus optimally reduce complications. Important points: This work emphasizes the analysis of risk factors, including the patient, the disease, and the treatment, according to stratification systems such as MASCC and CISNE. In addition, the clinical and microbiological foundations were evaluated to categorize the patient and include prophylactic support measures for the most frail groups, reducing the high risk of severe complications. Conclusion: Neutropenia is an undesirable adverse event in managing oncohaematological treatment. The MASCC and CISNE risk stratification systems are valuable tools for selecting low-risk patients. However, other factors, such as the type of tumor and infection, may influence the stratification. Therefore, it is essential to manage each patient individually. The initiation of antimicrobial prophylaxis and the use of FECG can help reduce morbidity and mortality.

A Case of Cutaneous Leukocytoclastic Vasculitis Associated with Granulocyte Colony-Stimulating Factor: An Unusual Presentation

Drug-induced vasculitis is an inflammation of small-sized blood vessel caused by the use of drugs. It accounts for approximately 10% of acute cutaneous vasculitis. Propylthiouracil, hydralazine, and allopurinol have been widely known as causative agents. The most common clinical feature of drug-induced vasculitis is palpable purpura on lower extremities. A 66-year-old Korean female presented with erythematous nodules on upper chest and back. She had been on medication for multiple myeloma. Laboratory results showed neutropenia. After a single injection of filgrastim (recombinant granulocyte colony-stimulating factor), she developed cutaneous lesions with concurrent increase in absolute neutrophil count. A skin biopsy revealed leukocytoclastic vasculitis. After discontinuation of filgrastim injection, her skin lesions disappeared spontaneously.

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

Biosimilar Filgrastim for Progenitor-Cell Mobilization prior to Autologous Transplantation: Retrospective Analysis of Patients with Multiple Myeloma and Lymphomas / Filgrastim Biossimilar para Mobilização de Células Progenitoras antes do Transplante Autólogo: Análise Retrospectiva de Pacientes com Mieloma Múltiplo e Linfomas / Filgrastim Biosimilar para la Movilización de Células Progenitoras antes del Trasplante Autólogo: Análisis Retrospectivo de Pacientes con Mieloma Múltiple y Linfomas

Introduction: Filgrastim, which plays a key role in peripheral blood progenitor cell (PBPC) harvesting, has been available for nearly 25 years, and several filgrastim biosimilars are available. Objective: We assessed whether a biosimilar filgrastim (Filgrastine®) was associated with effective mobilization in patients undergoing PBPC collection for autologous transplantation. Method: We reviewed the charts of patients with multiple myeloma and lymphomas treated at three institutions in Brazil. The primary outcome (mobilization success rate, MSR) was the proportion of patients in the intention-to-treat (ITT) group in whom at least 2 x 106 CD34+cells/Kg were harvested by leukapheresis on days 5 and/or 6. The per-protocol (PP) group comprised patients who received at least 4 days of Filgrastine and had at least one CD34+ count on days 5 or 6. Results: The daily dose of Filgrastine (on D1, with few changes thereafter) ranged from 8.5 to 28.9 mcg/Kg in the 52 patients in the ITT group, with a median of 13.8 mcg/Kg; 51 patients received at least four doses. A mean of 2.84±1.97 x 106 CD34+cells/Kg were harvested. MSR was 53.9% (95%CI, 39.5%-67.8%) in the ITT group and 62.2% (95%CI, 46.5%-76.2%) in the 45 patients in the PP group. Mobilization was considered effective by investigators in 80.8% of patients in the ITT group and 88.9% of those in the PP group. Conclusion: Despite the study's observational design, the results suggest that Filgrastine® is associated with the expected success rates in PBPC collection for autologous transplantation.

Introdução: O filgrastim, que desempenha um papel fundamental na coleta de células progenitoras de sangue periférico (CPSP), está disponível há quase 25 anos, e existem vários biossimilares de filgrastim sendo comercializados. Objetivo: Avaliar se um filgrastim biossimilar (Filgrastine®) foi associado com mobilização efetiva em pacientes submetidos à coleta de CPSP para transplante autólogo de medula óssea. Método: Foram revisados os prontuários de pacientes com mieloma múltiplo e linfomas tratados em três instituições no Brasil. O desfecho primário (taxa de sucesso de mobilização) foi a proporção de pacientes na população intenção de tratar (ITT), em que pelo menos 2 x 106 células CD34+/kg foram coletadas por leucaférese nos dias 5 e/ou 6. A população per protocolo (PP) foi composta por pacientes que receberam pelo menos quatro dias de Filgrastine e tiveram pelo menos uma contagem de CD34+ nos dias 5 ou 6. Resultados: A dose diária de Filgrastine (no D1, com pequenas alterações subsequentes) variou de 8,5 a 28,9 mcg/Kg nos 52pacientes na população ITT, com uma mediana de 13,8 mcg/Kg; 51 pacientes receberam pelo menos quatro doses. Uma média de 2,84±1,97 x 106 células CD34+/kg foram coletadas. A taxa de sucesso de mobilização foi de 53,9% (IC 95%, 39,5% a 67,8%) na população ITT e 62,2% (IC 95%, 46,5% a 76,2%) nos 45 pacientes da população PP. A mobilização foi considerada efetiva pelos pesquisadores em 80,8% dos pacientes da população ITT e 88,9% daqueles na população PP. Conclusão: Apesar de sua natureza observacional, este estudo sugere que Filgrastine esteja associado com as taxas de sucesso esperadas na coleta de CPSP para transplante autólogo de medula óssea.

Introducción: El filgrastim, que desempeña un papel fundamental en la colecta de células progenitoras de sangre periférica (CPSP), está disponible desde hace casi 25 años y existen varios biosimilares de filgrastim siendo comercializados. Objetivo: Se evaluó si un filgrastim biosimilar (Filgrastine®) se asoció con una movilización efectiva en pacientes sometidos a la colecta de CPSP para el trasplante autólogo de médula ósea. Método: Se revisaron los prontuarios de pacientes con mieloma múltiple y linfomas tratados en tres instituciones en Brasil. El resultado primario (tasa de éxito de movilización) fue la proporción de pacientes en la población intención de tratar (ITT) en que al menos 2 x 106 células CD34+/kg fueron obtenidas por leucoféresis en los días 5 y/o 6. La población por protocolo (PP) fue compuesta por pacientes que recibieron por lo menos 4 días de Filgrastine y tuvieron al menos un recuento de CD34 + en los días 5 o 6. Resultados: La dosis diaria de Filgrastine (en el D1, con pequeños cambios subsiguientes) varió de 8, 5 a 28,9 mcg/Kg en los 52 pacientes en la población ITT, con una mediana de 13,8 mcg / Kg; 51 pacientes recibieron al menos cuatro dosis. Se obtuvo una media de 2,84±1,97 x 106 células CD34+/kg. La tasa de éxito de movilización fue del 53,9% (IC 95%, 39,5% a 67,8%) en la población ITT y el 62,2% (IC 95%, 46,5% a 76,2%), en los 45 pacientes de la población PP. La movilización fue considerada efectiva por los investigadores en el 80,8% de los pacientes de la población ITT y el 88,9% de aquellos en la población PP. Conclusión: A pesar de su naturaleza observacional, este estudio sugiere que Filgrastine está asociado con las tasas de éxito esperadas en la recolección de CPSP para trasplante autólogo de médula ósea.

Bendamustine, etoposide, and dexamethasone to mobilize peripheral blood hematopoietic stem cells for autologous transplantation in non-Hodgkin lymphoma

BACKGROUND: Bendamustine is a chemotherapeutic agent that has shown broad activity in patients with lymphoid malignancies. It contains both alkylating and nucleoside analog moieties, and thus, is not commonly used for stem cell mobilization due to concerns that it may adversely affect stem cell collection. Here we describe the lymphoma subset of a prospective, non-randomized phase II study of bendamustine, etoposide, and dexamethasone (BED) as a mobilization agent for lymphoid malignancies. METHODS: This subset analysis includes diffuse large B-cell lymphoma (N=3), follicular lymphoma (N=1), primary mediastinal B-cell lymphoma (N=1), and NK/T-cell lymphoma (N=1). Patients received bendamustine (120 mg/m² IV d 1, 2), etoposide (200 mg/m² IV d 1–3), and dexamethasone (40 mg PO d 1–4) followed by filgrastim (10 mcg/kg/d sc. through collection). RESULTS: We successfully collected stem cells from all patients, with a median of 7.9×10⁶/kg of body weight (range, 4.4 to 17.3×10⁶/kg) over a median of 1.5 days (range, 1 to 3) of apheresis. All patients who received transplants were engrafted using kinetics that were comparable to those of other mobilization regimens. Three non-hematologic significant adverse events were observed in one patient, and included bacterial sepsis (grade 3), tumor lysis syndrome (grade 3), and disease progression (grade 5). CONCLUSION: For non-Hodgkin lymphoma, mobilization with bendamustine is safe and effective.

Trasplante de médula ósea alogénico en un paciente con fusariosis diseminada y leucemia mieloide aguda / Allogeneic hematopoietic cell transplantation in a patient with disseminated fusariosis and acute myeloid leukemia

La infección diseminada por Fusarium se ha convertido en un problema creciente en las personas con neoplasias hematológicas malignas, principalmente en pacientes con leucemias agudas; se describen cada vez más casos en aquellos sometidos a un trasplante de médula ósea. No existe un tratamiento óptimo establecido para la fusariosis diseminada. La mortalidad global comunicada de esta infección oscila entre el 50 y el 80%. Se presenta a continuación el caso de un paciente de sexo masculino de 29 años, con diagnóstico de leucemia mieloide aguda, que presenta como complicación una fusariosis diseminada, y logra sobrellevar un trasplante alogénico de médula ósea en el Hospital Italiano de San Justo (Argentina) de forma exitosa. (AU)

Disseminated fusariosis has become an increasing problem in people with hematopoietic neoplasms, mainly in patients affected by acute leukemias, and even more in those who undergo hematopoietic cell transplantation. There is not an optimal treatment for disseminated fusariosis. The global mortality described in the literature is between 50% and 80%. We introduce a case of a 29 year old patient with diagnosis of acute myeloid leukemia complicated with disseminated fusariosis, who copes with an allogeneic hematopoietic cell transplantation with a successful outcome in the "Hospital Italiano de San Justo" (Argentina). (AU)

Characterization and comparability of biosimilars: a filgrastim case of study and regulatory perspectives for Latin America

Background: Developing countries have an estimate of ten times more approved biosimilars than developed countries. This disparity demands the need of an objective regulation that incorporates health policies according to the technological and economical capabilities of each country. One of the challenges lies on the establishment of comparability principles based on a physicochemical and biological characterization that should determine the extent of additional non-clinical and clinical studies. This is particularly relevant for licensed biosimilars in developing countries, which have an extensive clinical experience since their approval as generics' in some cases more than a decade. To exemplify the current status of biosimilars in Mexico' a characterization exercise was conducted on licensed filgrastim biosimilars using pharmacopeial and extended characterization methodologies. Results: Most of the evaluated products complied with the pharmacopeial criteria and showed comparability in their Critical Quality Attributes (CQAs) towards the reference product. These results were expected in accordance with their equivalent performance during their licensing as generics. Accordingly' a rational approval and registration renewal scheme for biosimilars is proposed, that considers the proper identification of CQAs and its thoroughly evaluation using selected techniques. Conclusions: This approach provides support to diminish uncertainty of exhibiting different pharmacological profiles and narrows or even avoids the necessity of comparative clinical studies. Ultimately, this proposal is intended to improve the accessibility to high quality biosimilars in Latin America and other developing countries.

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)

Duration of filgrastim prophylaxis for chemotherapy-induced neutropenia and its predictors / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the duration of preventive filgrastim administration as support for chemotherapy and its affecting factors.</p><p><b>METHODS</b>Single institutional data from a phase Ⅱ clinical trial and a phase Ⅲ clinical trial of pegylated filgrastim were combined. In the two randomized cross-over trials, patients with previously untreated cancer received two cycles of chemotherapy of the same regimen. In the study group, the patients received a single subcutaneous injection of 100 μg/kg pegylated filgrastim, and in the control group, they received daily subcutaneous injections of 5 μg/kg filgrastim.</p><p><b>RESULTS</b>In 53 chemotherapy cycles, the median duration of filgrastim administration was (9.57±2.10)d. 83.0% (44/53) of them received filgrastim for 7-11 days. Patients with baseline absolute neutrophil count of <4×10(9)/L or body mass index less than 22 received a longer filgrastim prophylaxis(P<0.05). RESULTS of multivariate analysis showed that the baseline absolute neutrophil count is associated with the time of filgrastim administration(P=0.019). The most common adverse event of rhG-CSF was skeletal pain, generally mild and no treatment-related death occurred.</p><p><b>CONCLUSIONS</b>The median duration of filgrastim support for chemotherapy was 10 days. Patients with lower baseline neutrophil count require a longer filgrastim prophylaxis.</p><p><b>TRIAL REGISTRATION</b>: ClinicalTrials.gov identifier, NCT01285219.</p>

A retrospective analysis of autologous peripheral blood hematopoietic stem cell mobilizations and collections in 149 multiple myeloma patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the results and influential factors of mobilization and harvesting of autologous peripheral blood stem cell in patients with multiple myeloma (MM).</p><p><b>METHODS</b>Retrospective analysis of peripheral blood stem cell collection data [CD34⁺ cells collected, successful mobilization rate (CD34⁺ cells≥2×10⁶/kg body weight), good mobilization rate (CD34⁺ cells≥5×10⁶/kg body weight)] of 149 multiple myeloma patients who were treated with cyclophosphamide (CTX) or E-CHOP (etoposide+ CTX+epirubicin+vindesine+prednisone) chemotherapy combined with G-CSF mobilization from January 1998 to March 2014. The relevance between gender, age, subtype, DS staging, ISS staging, treatment before mobilization, disease status at mobilization, regiment of mobilizationand the collection results was analyzed.</p><p><b>RESULTS</b>A total of 177 stem cell mobilizations were performed in 149 MM patients, the median CD34⁺ cells harvested were 3.20 (0.13-22.34)×10⁶/kg body weight (BW), successful mobilization rate and good mobilization rate were 74.5% and 27.5%, respectively. The single logistic regression analysis showed that gender, age （>60 ys vs ≤60 ys）, subtype, DS staging (III vs II+I), ISS staging (III vs II+I) and regiment of mobilization (E-CHOP+G-CSF vs ID-CTX+G-CSF) were not correlated with the cell collection or successful mobilization rate (P>0.05). However, successful collection rate of single harvest in old patients (age>60 ys) was lower (P<0.05), andthe good mobilization rate in patients at ISS stage III was lower (P<0.05). The collection results of patients with fewer cycles of treatment (treatment before mobilization ≤6 cycles) and optimal disease status (disease status at mobilization ≥partial remission) were much better. Analysis of logistic factors revealed that treatment efficacy before mobilization affected success rate of collection (P=0.006). Risk of collection failure in patients who received more than 6 cycles of treatment before mobilization was high (OR 3.57, 95% CI 1.45-8.78).</p><p><b>CONCLUSION</b>Gender, age, subtype, DS staging, ISS staging and mobilization regimen did not influence MM patients peripheral blood stem cell collection; but old patients may need twice mobilizations to collect sufficiently. Few cycles of treatment and stable disease status before mobilization is favorable to the mobilization and collection of peripheral blood stem cells.</p>

Utility Analysis for Pegfilgrastim in DLBCL Patients on R-CHOP Regimen

OBJECTIVE: This study was designed to compare pegfilgrastim and filgrastim in diffuse large B-cell lymphoma (DLBCL) patients treated with a rituximab with cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (R-CHOP) regimen in terms of clinical efficacy and cost-effectiveness. METHOD: Clinical efficacy was measured by trough level of absolute neutrophil count (ANC), days of ANC under 50% of baseline value, days of ANC under 90% of baseline value, duration of ANC recovery to baseline value, days of ANC less than 0.5 x 109 cells/L, and difference of peak and trough level of ANC during 1 cycle of R-CHOP regimen. To evaluate cost-effectiveness, total prices of used filgrastim and pegfilgrastim within 1 cycle of R-CHOP were analyzed. RESULTS: In terms of clinical efficacy, trough level of ANC and days to ANC recovery showed statistical significance. The median trough levels of ANC with administration of filgrastim and pegfilgrastim were 0.18 and 1.94 (p = 0.021), respectively, and the median durations of ANC recovery to baseline value were 5.5 days and 2 days (p = 0.023), respectively. For the median days of ANC under 50% of baseline value, days of ANC under 90% of baseline value, days of ANC less than 0.5 x 109 cells/L, and difference of peak and trough level of ANC during 1 cycle of R-CHOP, the pegfilgrastim group performed better than the filgrastim group. However the difference was not statistically significant. In terms of overall expense during 1 cycle of R-CHOP, pegfilgrastim is about 3.43 times more expensive than filgrastim. CONCLUSION: Pegfilgrastim is more efficient than filgrastim in terms of clinical efficacy. In terms of prices, pegfilgrastim is more expensive than filgrastim for patients, but it is more convenient in clinical use. Therefore, pegfilgrastim should be the preferred choice of G-CSF for neutropenic patients. Further comparative study of pegfilgrastim and filgrastim is needed.

Safety of polyethylene glycol recombinant human granulocyte colony-stimulating factor in treating non-small cell lung cancer patients at I b stage

OBJECTIVE@#To investigate resistance and safety of HHPG-19K in treating non-small cell lung cancer patients.@*METHODS@#A total of 30 cases were selected and randomly divided into 5 groups: three HHPG-19K groups of different dosage (60 μg/kg/day, 100 μg/kg/day, 200 μg/kg/day), positive control group (Filgrastim, namely G-CSF5 μg/kg/day) and negative control group. Safety indexes of 5 groups were observed and compared.@*RESULTS@#All patients had adverse event (100%) in three HHPG-19K groups, and increased ALP, ALT and AST were main events. The degree was mild to moderate. There was no significant difference in the incidence of adverse event between dosage groups and positive control group no difference. But the incidence of negative control group was 13%, which was significantly lower than dosage groups and positive control group.@*CONCLUSIONS@#non-small cell lung cancer patients have satisfactory tolerance to HHPG-19K, and have no resistance. Besides, dosage at 100 μ g/kg is the most safe.

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.

Role of granulocyte colony-stimulating factor [G-CSF]/Filgrastim as an adjunct in chronic hepatitis C management

Drug-induced hematotoxicity is the commonest reason for reducing the dose or withdrawing interferon [IFN] therapy in a case of chronic hepatitis C thus depriving the patient of a possible cure. Traditionally, severe neutropenia has been considered an absolute contraindication to start antiviral therapy. Since the advent of adjunct therapy with Granulocyte-colony stimulating factor, the same is not true any more. Some recent landmark studies have used this adjunct therapy to help avoid antiviral dose reductions. although, addition of this adjunct therapy has been shown to significantly increase the overall cost of the treatment, if the infection is cured at the end of the day, this extra cost is worth bearing. Although, more studies are needed to refine the true indications of this adjunct therapy, determine the best dose regimen, quantify the average extra cost and validate that whether or not the addition of this therapy increases the sustained virologic response rates achieved, the initial reports are encouraging. Therefore, although not recommended on routine basis, some selected patients may be given the benefits of these factors. In this article, a review of the current literature on this subject is given followed by few suggested recommendations at the end to help develop local guidelines

Neutropenia in children / 소아과

Neutropenia is defined as an absolute neutrophil count (ANC) of <1,500/microliter, and the severity of neutropenia generally can be graded as mild (1,000-1,500/microliter), moderate (500-1,000/microliter), or severe (<500/microliter). This stratification aids in predicting the risk of pyogenic infection because the susceptibility to life-threatening infections is significantly increased in patients with prolonged episodes of severe neutropenia. Especially cancer-related neutropenia carry significant mortality. Neutropenia can develop under various conditions such as decreased bone marrow production, the sequestering of neutrophils, and increased destruction of neutrophils in the peripheral blood. Neutropenia is classified according to the etiology as congenital or acquired, with the latter further defined according to the etiology or pathology. The clinical result is increased risk for infection, which is directly proportional to the severity and duration of the neutropenia. The typical workup of neutropenia starts with a 6-week period in which complete blood counts are measured twice weekly to document the persistence of the neutropenia and whether a cyclic pattern is present. When persistent neutropenia is diagnosed and no spontaneous recovery occurs within 3 months, a more extensive evaluation is advised. Treatment is usually unnecessary for most patients with severe neutropenia, as the majority of patients have a good prognosis. However, for patients who have severe and frequent infections, treatment with filgrastim may prevent infectious complications and improve quality of life.

Factors Influencing Peripheral Blood Stem Cell Collection / 종양간호학회지

PURPOSE: Peripheral blood stem cell transplantation (PBSCT) has been widely used. The optimal time for collection is a critical factor to obtain proper counts of CD34 cell by peripheral blood stem cell collection (PBSC). The purpose of this study was to identify the factors influencing peripheral blood stem cell collection in order to figure out the more effective timing for PBSC. METHOD: The subjects of this study were 189 patients undergoing 3 leukapheresis from January 28, 2005 to December 31, 2006. Group's characteristics, checkup opinion of pre-peripheral blood on the day of harvest & outcome of PBSC were analyzed and evaluated using SAS statistics program after grouping patients as below; group 1-CD34 cell counts or =4x10(6)/kg (n=63). RESULTS: Based on outcome of peripheral blood stem cell according to diagnosis, acute myelocytic leukemia (AML) was 65.5% at Group 1, Lymphoma was 21.7% at Group 2 and multiple myeloma (MM) was 70.8% at Group 3. There were significant differences in CD34 cell counts according to diagnosis (p=0.00004). Type of cytokine mobilization according to diagnosis, Lenograsim was using 62.5% of MM & 38.2% of AML and filgrastim is using 22.0% of AML only. Circular peripheral blood CD34 cell counts prior to harvest was 258.1/microliter at Group 3 which was much higher comparing to Group 1 (10.5/microliter) and Group 2 (39.9/microliter) (p<0.001). TNC counts of collected peripheral blood stem cell was 15.36x10(6)/kg at Group 3 microliter and it's much higher than Group 2 (13.16x10(6)/kg) and Group 1 (12.36x10(6)/kg) (p=0.083). There was no significant difference in MNC counts inbetween 3 groups. CONCLUSIONS: Circular peripheral blood CD34+ cell counts prior to harvest was much higher at Group 3 than Group 1 and Group 2. Therefore, the number of CD34+ cells on the day of harvest can be used as an accurate predictor for peripheral blood stem cell.

Comparing efficacy and side effects of Pd grastim and neupogen for prevention of neutropenia after chemotherapy in children

G-CSF is one of the new medications that may reduce duration and severity of neutropenia after chemotherapy. Two forms of G-CSF are now available in Iran: Neupogen [original form], and new production of Iran named Pd-Grastin. We decided to compare the efficacy and side effects of these two forms of the drug. Absolute Neutrophil count [ANC], total WBC, platelet count [on the 15th day of chemotherapy], and event of fever and neutropenia in this period, were measured after 60 courses of chemotherapy and 4 days of G-CSF, in two separate but the same patients groups, Pd-Grastim [group 1] and Neupogen [group 2]. Mean values of WBC count, ANC, and platelet count were similar [P.V.>0.05]. No significant difference was observed for episodes of neutropenia [ANC <500], event of fever and neutropenia, and days of hospitalization between these groups. Effectiveness and also side effects of Pd-Grastin and Neupogen were similar. Lower cost of Pd-Grastim was the only significant difference between these two forms of G-CSF. Pd-Grastim may be preferred to Neupogen in Iran, because of the same effectiveness but lower cost