Zarzio Ameliorates Non-alcoholic Fatty Liver Induced By a High Fat Diet in a Rat Experimental Model: A Histological and Immunohistochemical Study

SUMMARY: The therapeutic effect of a granulocyte-colony stimulating factor (G-CSF) biosimilar drug, zarzio, on non-alcoholic fatty liver disease (NAFLD) in a rat model was investigated in this study. Thirty-two rats were randomly divided into four groups. Groups I and II were fed a standard laboratory diet, whereas groups III and IV were fed a high fat diet (HFD) for 14 weeks. After 12 weeks of feeding, groups I and III were administered normal saline, and groups II and IV were intraperitoneally administered zarzio (200 mg/kg/day) for two consecutive weeks. Hematoxylin-eosin (H&E) staining was used to assess hepatic and pancreatic morphology in all groups, oil red O (ORO) staining for lipid accumulation, Masson's staining for fibrosis, and immunohistochemistry assay for hepatic protein expression of insulin receptor substrate 1 (IRS1), nuclear factor erythroid 2-related factor 2 (Nrf2), tumour necrosis factor alpha (TNF-α) and pancreatic caspase-3. The NAFLD rats (group III) developed hepatic steatosis with increased lipid accumulation, perisinusoidal fibrosis, upregulated IRS1, TNF-α (all P<0.05) without a significant increase in Nrf2 protein expression compared with normal control. In comparison, model rats treated with zarzio (group IV) showed significant rejuvenation of the hepatic architecture, reduction of fat accumulation, and fibrosis. This was accompanied by the upregulation of Nrf2, downregulation of IRS1 and TNF-α protein expression (all P<0.05). No correlation was detected between NAFLD and non-alcoholic fatty pancreas disease (NAFPD). However, the pancreatic β-cells in group III showed increased caspase-3 expression, which was decreased (P<0.05) in group IV. In conclusion, zarzio ameliorates NAFLD by improving the antioxidant capacity of liver cells, reducing hepatic IRS1, TNF-α protein expression and pancreatic β-cells apoptosis, suggesting that zarzio could be used as a potential therapy for NAFLD.

En este estudio se investigó el efecto terapéutico de un fármaco biosimilar del factor estimulante de colonias de granulocitos (G-CSF), zarzio, sobre la enfermedaddel hígado graso no alcohólico (NAFLD) en un modelo de rata. Treinta y dos ratas se dividieron aleatoriamente en cuatro grupos. Los grupos I y II fueron alimentados con una dieta estándar de laboratorio, mientras que los grupos III y IV fueron alimentados con una dieta alta en grasas (HFD) durante 14 semanas. Después de 12 semanas de alimentación, a los grupos I y III se les administró solución salina normal, y a los grupos II y IV se les administró zarzio por vía intraperitoneal (200 mg/kg/ día) durante dos semanas consecutivas. Se utilizó tinción de hematoxilina-eosina (H&E) para evaluar la morfología hepática y pancreática en todos los grupos, tinción con rojo aceite O (ORO) para la acumulación de lípidos, tinción de Masson para la fibrosis y ensayo de inmunohistoquímica para la expresión de la proteína hepática del sustrato 1 del receptor de insulina (IRS1), factor nuclear eritroide 2 relacionado con el factor 2 (Nrf2), factor de necrosis tumoral alfa (TNF-α) y caspasa-3 pancreática. Las ratas NAFLD (grupo III) desarrollaron esteatosis hepática con aumento de la acumulación de lípidos, fibrosis perisinusoidal, IRS1 y TNF-α regulados positivamente (todos P <0,05) sin un aumento significativo en la expresión de la proteína Nrf2 en comparación con el control normal. En comparación, las ratas modelo tratadas con zarzio (grupo IV) mostraron un rejuvenecimiento significativo de la arquitectura hepática, una reducción de la acumulación de grasa y fibrosis. Esto estuvo acompañado por la regulación positiva de Nrf2, la regulación negativa de la expresión de la proteína IRS1 y TNF-α (todas P <0,05). No se detectó correlación entre NAFLD y la enfermedad del páncreas graso no alcohólico (NAFPD). Sin embargo, las células β pancreáticas en el grupo III mostraron una mayor expresión de caspasa-3, que disminuyó (P <0,05) en el grupo IV. En conclusión, zarzio mejora la NAFLD al mejorar la capacidad antioxidante de las células hepáticas, reduciendo el IRS1 hepático, la expresión de la proteína TNF-α y la apoptosis de las células β pancreáticas, lo que sugiere que zarzio podría usarse como una terapia potencial para la NAFLD.

The safety and clinical efficacy of recombinant human granulocyte colony stimulating factor injection for colon cancer patients undergoing chemotherapy

Summary Objective: The present study was designed to evaluate safety and efficacy of recombinant human granulocyte colony stimulating factor (G-CSF) injection and whether this regimen could reduce the incidence of adverse events caused by chemotherapy. Method: A total of 100 patients with colon cancer who were treated with chemotherapy in our hospital from January 2011 to December 2014 were randomly divided into two groups, with 50 patients in each group. The patients in the treatment group received G-CSF 24 hours after chemotherapy for consecutive three days; the patients in the control group received the same dose of normal saline. Routine blood tests were performed 7 days and 14 days after chemotherapy. Results: Compared with the control group, the incidences of febrile neutropenia and leukocytopenia in the treatment group were significantly lower (p<0.05). In addition, the incidence of liver dysfunction in the treatment group was lower than that of the control group, without statistical significance. The incidence of myalgia in the treatment was higher than that of the control group without statistical significance. Conclusion: The present study indicated that G-CSF injection after chemotherapy is safe and effective for preventing adverse events in colon cancer patients with chemotherapy.

Assessment of Autonomic Function by Phase Rectification of RRInterval Histogram Analysis in Chagas Disease / Avaliação da Função Autonômica na Doença de Chagas Através da Análise de Histogramas de Intervalos RR com Retificação de Fase

Background: In chronic Chagas disease (ChD), impairment of cardiac autonomic function bears prognostic implications. Phase‑rectification of RR-interval series isolates the sympathetic, acceleration phase (AC) and parasympathetic, deceleration phase (DC) influences on cardiac autonomic modulation. Objective: This study investigated heart rate variability (HRV) as a function of RR-interval to assess autonomic function in healthy and ChD subjects. Methods: Control (n = 20) and ChD (n = 20) groups were studied. All underwent 60-min head-up tilt table test under ECG recording. Histogram of RR-interval series was calculated, with 100 ms class, ranging from 600–1100 ms. In each class, mean RR-intervals (MNN) and root-mean-squared difference (RMSNN) of consecutive normal RR-intervals that suited a particular class were calculated. Average of all RMSNN values in each class was analyzed as function of MNN, in the whole series (RMSNNT), and in AC (RMSNNAC) and DC (RMSNNDC) phases. Slopes of linear regression lines were compared between groups using Student t-test. Correlation coefficients were tested before comparisons. RMSNN was log-transformed. (α < 0.05). Results: Correlation coefficient was significant in all regressions (p < 0.05). In the control group, RMSNNT, RMSNNAC, and RMSNNDC significantly increased linearly with MNN (p < 0.05). In ChD, only RMSNNAC showed significant increase as a function of MNN, whereas RMSNNT and RMSNNDC did not. Conclusion: HRV increases in proportion with the RR-interval in healthy subjects. This behavior is lost in ChD, particularly in the DC phase, indicating cardiac vagal incompetence. .

Fundamento: Na doença de Chagas (DCh) crônica, a função autonômica cardíaca está frequentemente comprometida e traz implicações quanto ao prognóstico. A retificação de fase da série de intervalos RR isola as influências simpática (fase de aceleração – AC) e parassimpática (fase de desaceleração – DC) na modulação autonômica cardíaca. Objetivo: Este estudo investigou a variabilidade da frequência cardíaca (VRR) como função dos intervalos RR, para avaliar a função autonômica em indivíduos saudáveis e com DCh. Métodos: Os grupos controle (n = 20) e com DCh (n = 20) foram estudados. Todos fizeram o teste de inclinação ortostática de 60 minutos, com o registro do ECG. O histograma da série de intervalos RR dividido em classes de 100 ms, variando de 600 a 1100 ms foi calculado. Para cada classe, foram calculados os intervalos RR médios (MNN) e a diferença média quadrática (RMS) entre os intervalos RR normais que se encaixavam naquela classe. A média de todos os valores de RMS foi analisada como uma função dos MNN na série inteira (RMST) e nas fases de aceleração (RMSAC) e desaceleração (RMSDC). A inclinação das linhas de regressão linear foi comparada entre grupos através do teste t de Student. Os coeficientes de correlação foram testados antes das comparações. A RMS sofreu transformação logarítmica (α < 0,05). Resultados: O coeficiente de correlação foi significativo em todas as regressões (p < 0,05). No grupo controle, a RMST, a RMSAC e a RMSDC aumentaram de forma significativa proporcionalmente ao MNN (p < 0,05). No grupo com DCh, apenas a RMSAC mostrou um aumento significativo como função do MNN, enquanto a RMST e a RMSDC não aumentaram significativamente. Conclusão: A VRR aumenta proporcionalmente ao intervalo RR em indivíduos saudáveis. Este comportamento é perdido na DCh, especialmente na DC, indicando incompetência vagal cardíaca. .

Efficacy and Safety of Pegfilgrastim in Indian Patients.

Context: Pegfilgrastim, a pegylated recombinant granulocyte colony stimulating factor, promotes the hematopoietic recovery after cytotoxic chemotherapy and is marketed in India as PegstimTM. Aims: This post marketing surveillance study was undertaken to evaluate the efficacy and safety of PegstimTM in clinical practice in Indian patients. Material and Methods: Investigators participating in this post marketing surveillance were asked to capture data of all the patients who were given PegstimTM along with cytotoxic chemotherapy for their underlying malignancy. PegstimTM was given as a single subcutaneous dose approximately 24 hours after administration of cytotoxic chemotherapy and patients were followed up for 14 days with blood counts at baseline and every alternate day. Each cycle of chemotherapy in which PegstimTM was administered was considered as a distinct patient entity for efficacy and safety analysis. Results: PegstimTM injections were used in 213 patients and led to an increase in Absolute Neutrophil Count (ANC) as early as 2 days after administration of the drug with mean percent increase in ANC of 129.8 ± 210.9% at the end of 14 days. The overall incidence of moderate-severe (grade III/IV) febrile neutropenia in the total population studied was 6.1% (13 patients). Intravenous antibiotics were used in 10 (4.7%) patients while 4 (1.9%) patients required hospitalization. A total of 57 adverse events were reported in 32 patients during the entire course of the study, the most common being musculoskeletal pain in 22 (10.3%) patients. Conclusions: The results from this post marketing surveillance study support the efficacy and tolerability of PegstimTM used for preventing neutropenia across various tumor types and regimens in Indian patients.

Comparación de la actividad de 2 factores estimuladores de colonias de granulocitos de producción nacional: Hebervital y Leukocim / Comparison of the activity of 2 domestic- production factors for granulocyte colonies: Hebervital and Leukocim

En 35 pacientes que debían recibir terapia celular regenerativa se evaluó el efecto estimulante de 2 factores estimuladores de colonias de granulocitos de producción cubana: Hebervital y Leukocim, para la movilización de células madre hematopoyéticas hacia la sangre periférica. Los pacientes se seleccionaron de forma aleatoria en 2 grupos de tratamiento y se les suministró por vía subcutánea una dosis total de 40 mg/kg distribuidos en 4 subdosis de 10 mg/kg administrados cada 12 horas. Se realizó el conteo de las células mononucleares y células CD34+ en sangre periférica mediante citometría de flujo, antes y después de la estimulación. No se encontraron diferencias estadísticamente significativas en los conteos de las células CD34+ obtenidas posestimulación con el Hebervital y el Leukocim

In 35 patients who should have received regenerative cell therapy, it was evaluated the effect of 2 domestic production granulocyte colony stimulating factors: Leukocim and Hebervital for the mobilization of hematopoietic stem cells into peripheral blood. Patients were randomly selected into 2 treatment groups and were given a total dose of 40 mg/kg in 4 sub-doses of 10 mg/kg subcutaneously administered every 12 hours. Count was performed for mononuclear cells and CD34+ cells in peripheral blood by flow cytometry before and after stimulation. There were no statistically significant differences in the counts of CD34+ cells obtained after stimulation with Hebervital and Leukocim

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

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

Comparison of two regimens of RhG-CSF in neutropenic neonatal septicemia: a randomized clinical trial

Considering the 50% mortality rate of neonatal septicemia associated with neutropenia and increasing resistance to antibiotics, simultaneous antibiotic therapy strategies are becoming more important. However, few studies have been performed to evaluate effectiveness of RhG-CSF in the treatment of neutropenia in neonates. This randomized clinical trial was performed on 40 neutropenic neonates with septicemia who were hospitalized in Vali-e-Asr and Mirza Koochak Khan Hospitals [Tehran, Iran]. The neonates were randomly divided into two equal groups RhG-CSF was administered as a subcutaneous single dose of 10 micro g/kg/s.c. to neonates in group A and as 10 micro g/kg/s.c./day once daily for 3 days to neonates in group B. CBC and differential count was checked 6, 24 and 48 hours after the last dose. There was no significant difference in mean birth weight, gender, age, and risk factors between two groups. Neutropenia was improved 48 hours after the last dose, whilst there was no significant statistical difference between two groups [P>0.05]. The final outcome including death, duration of hospitalization and duration of antibiotics therapy after RhG-CSF administration did not differ between two groups [P>0.05]. The results of this study showed that administration of a single dose of RhG-CSF [10 micro g/kg] was effective in treating neonatal septicemic neutropenia

Premio Dr. Abraham Isaías Kohan - XIII Congreso Argentino de Medicina Transfusional. Proceso de colecta de células progenitoras hematopoyéticas de sangre periférica en pediatría / Dr. Abraham Isaías Kohan Award - XIII Argentine Congress of Transfusion Medicine. Stem cell collections and associated processes in a pediatric population

Fundamento: El trasplante de células progenitoras hematopoyéticas, es una terapéutica utilizada para el tratamiento de pacientes con enfermedades hematológicas y oncológicas, entre otras. Las células progenitoras hematopoyéticas de sangre periférica se obtienen mediante leucaféresis, previa movilización del donante con factores de crecimiento hematopoyético. Objetivos: Comunicar la experiencia de colectas de células progenitoras hematopoyéticas y los procesos asociados, en una población pediátrica candidata a trasplante autólogo o alogeneico. Material y Método: Se evaluaron 53 pacientes y/o donantes para realizar colecta de CPH, entre los años 2008 y 2011. Se tomó consentimiento informado para realizar los procedimientos. Todos fueron evaluados clínicamente y mediante estudios de laboratorio. El momento de colecta se determinó por el número de las células CD34+ en sangre periférica (óptimo 10 a 20 CD34+/uL) en los pacientes y/o donantes, la decisión se tomó en equi­po: médico tratante y de hemoterapia. Resultados: Fueron evaluados 53 candidatos, se realizó colecta en 40: Grupo I autólogo 29 (72,5 %) y Grupo II alogeneico 11 (27,5%). Se realizaron 61 colectas, 50 en Grupo I (82%) y 11 en Grupo II (18%). La mediana de la dosis de movilización con G-CSF fue 12,80 ug/ Kg /día (Rango: 10-25) aplicada entre 4 y 6 días. El recuento de CD34+ en los productos obtenidos resultó en una mediana 6,50 CD34+ x10 6/Kg de receptor (Rango: 1,31-38,34). Conclusiones: Los procesos y procedimientos empleados para obtener células progenitoras hematopoyéticas para el trasplante nos permitieron cumplir los objetivos dentro del programa de garantía de la calidad y obtener resultados clínicos deseados comparables a los publicados en la literatura en este campo.

Background: The hematopoietic stem cell transplantation is a therapy used to treat patients with blood diseases and cancer, among others. Hematopoietic progenitor cells from peripheral blood are obtained by leukapheresis after donor mobilization with hematopoietic growth factors. Objectives: Communicating the experience of stem cell collections and associated processes in a pediatric population candidate for autologous or allogeneic transplantation. Methods: 53 patients and / or donors were evaluated for collection between 2008 and 2011. Informed consent was taken. AII were clinically evaluated and we also performed some laboratory testing. The timing of collection was determined by the number of CD34+ peripheral blood (10 - 20 CD34+ cells /uL) and the decision was made as a team integrated by the physician in charge and the Blood Bank physician.Results: Of the 53 candidates, collection was performed in 40. Group I: autologous 29 (72.5%) and Group II allogeneic 11 (27.5%). 61 collections were made, 50 in Group I (82%) and 11 in Group II (18%). The median dosage of G-CSF mobilization was 12.80 ug/kg/day (range: 10-25) was administered for a period of 4 to 6 days. The CD34+ count in the products resulted in a median of 6,50 x 10 6 CD34+ /kg recipient (range: 1.31 to 38.34). Conclusions: The processes employed in obtaining hematopoietic progenitor cells allowed us to meet goals under the Quality Assurance Program and achieve satisfactory clinical results comparable to those reported in the literature of the field.

Toxic epidermal necrolysis and agranulocytosis: Rare adverse effects of ciprofloxacin.

Ciprofloxacin is one of the most commonly used antibacterial agents with relatively few side effects. Serious adverse reactions reported with ciprofloxacin are rare with an incidence of 0.6%. Recently we came across two rare adverse effects of ciprofloxacin, viz. toxic epidermal necrolysis and agranulocytosis. To our knowledge, a total of seven cases have been reported in the literature documenting an association between oral ciprofloxacin administration and toxic epidermal necrolysis. One case of granulocytopenia, four of pancytopenia and fifteen of leucopenia worldwide have been reported. With the use of ciprofloxacin becoming more and more widespread, these two rare but fatal complications of ciprofloxacin should be borne in mind.

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

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

Recombinant human granulocyte-macrophage colony-stimulating factor: effect of glycosylation on pharmacokinetic parameters

The pharmacokinetic behaviour of the non-glycosylated, bacterially-derived recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and the glycosylated mammalian product was studied after intra and extra vascular administration of a single dose in rodents. Each route of administration gave a different rhGM-CSF concentration-time profile. After extra vascular administration of equivalent doses, a higher peak concentration and faster elimination were observed in the group treated with the E. coli-derived cytokine. The faster elimination resulted in a return to pre-treatment plasma levels after 12 hrs, versus 48 hrs following the administration of glycosylated rhGM-CSF. After intravascular administration, clearance of rhGM-CSF was significantly decreased by the presence of carbohydrates. Non-significant differences in the terminal phase of the biphasic kinetics were found, but the distribution phase was significantly longer for the glycosylated form

High-dose Versus Low-dose Cyclophosphamide in Combination with G-CSF for Peripheral Blood Progenitor Cell Mobilization

BACKGROUND: To compare the mobilizing effects and toxicities of two different doses of cyclophosphamide (CY) plus lenograstim (glycosylated G-CSF), we performed a prospective randomized study by enrolling patients suffering with either high-risk Non-Hodgkin's lymphoma (NHL) or breast cancer undergoing ablative chemotherapy. METHODS: The NHL patients received 4 cycles of CHOP and the breast cancer patients received 2-3 cycles of FAC (FEC) adjuvant chemotherapy. Then, the patients were randomly allocated to receive CY 4 g/m2 (arm A) or 1.5 g/m2 (arm B) in combination with lenograstim. Large volume leukapheresis was carried out and it was continued daily until the target cell dose of 2x10 (6) CD34+ cell/kg was reached. RESULTS: Twenty-seven patients were enrolled in the study. The median number of leukaphereis sessions actually performed was 2.5 sessions in arm A and 3 sessions in arm B. The target cell dose was obtained with the median number of one leukapheresis session in both arms of the study (p=0.09). The collected number of CD34+ cells in the leukapheresis products was higher in arm A than arm B (22.4 vs. 9.9x10 (6) /kg, respectively, p=0.05). Grade III or IV leukopenia was present in 14/15 patients (94%) in arm A and in 1/12 patients (8%) in arm B (p< 0.0001). Grade III or IV thrombocytopenia was present in 8/15 patients (54%) in arm A, but this was not present in any patients of arm B (p=0.0004). Neutropenic fever occurred in 6/15 patients (40%) in arm A, and in 1/12 patients (8%) in arm B (p=0.09). The hematological recovery of the leukocytes and platelets after transplantation was not statistically different between the two doses. CONCLUSION: Low-dose CY plus lenograstim is a safe and effective mobilizing regimen.

Double Autologous Stem Cell Transplantation for Multiple Myeloma: A Korean Single Center Study

BACKGROUND: Although high dose chemotherapy coupled with an autologous stem cell transplantation (ASCT) is widely accepted as effective therapy for multiple myeloma (MM), few reports are available in Korea, especially in the area of double ASCT. We present the results of an institutional retrospective study of 12 patients with MM treated by double ASCT. METHODS: Eligible patients received induction therapy using vincristine, adriamycin, dexamethasone (VAD), and mobilization was performed using cyclophosphamide plus lenograstim. High-dose melphalan (total 200 mg/m2) was used to condition the ASCT. RESULTS: The median interval from diagnosis to ASCT was 6 months (range, 1.8-15.3 months). The median interval between the 1st and 2nd ASCT was 4.4 months (range 2.1-48.7 months). The median follow up was 18.3 months (range 8.1-50.5 months) for the nine surviving patients. No therapy-related mortality occurred. Following induction chemotherapy, two patients experienced CR. Following double ASCT, eight patients experienced CR. The 5 year OS was 59%. The median duration of event free survival was 2.13 years (95% CI, 0.84-3.42). CONCLUSION: Although the results of study did not demonstrate the advantage of double ASCT, this is the first report to outline the outcome of double ASCT for Korean MM patients.

Transplante celular para o tratamento de pacientes com insuficiência cardíaca / Cell transplantation for the treatment of patients with heart failure

Apesar de importantes avanços na terapêutica medicamentosa e cirúrgica de pacientes com insuficiência cardíaca, a persistência de significativas limitações justifica a busca por formas alternativas de tratamento. A observação da existência de processos de regeneração no miocárdio colocou a angiogênese, a terapia gênica e o transplante de células como possíveis formas de tratamento para pacientes com insuficiência cardíaca. Esses métodos têm como princípio a amplificação de mecanismo de regeneração do tecido miocárdico. Células-tronco são células primitivas que guardam as propriedades de se auto-regenerar ou de gerar outras células mais diferenciadas. Podem derivar de embriões (heterólogas) ou de indivíduos adultos (autólogas). A evidência acumulada de dados experimentais permitiu a realização de protocolos com o objetivo de se testar a factibilidade e a segurança do transplante celular autólogo em humanos. Apesar dos resultados promissores, ainda persistem algumas perguntas, como: ôQual tipo celular deve ser utilizado?ö, ôQual a melhor via de administração?ö, ôQual o papel de agentes adjuvantes?ö, ôQuando, na história natural da doença, a terapia celular teria maior efetividade?ö, ôQual a quantidade de células a serem administradas?ö, e ôQuantos ciclos de administração devem ser feitos e por quanto tempo?ö. Além disso, também precisa ser definido o papel das células-tronco embrionárias.

Very Severe Aplastic Anemia appearing after Thymectomy

Aplastic anemia is a rare complication of thymoma and is extremely infrequent after thymectomy. We present a case of a 60-year-old woman with very severe aplastic anemia appearing sixteen months after thymectomy for a thymoma. She underwent thymectomy for a thymoma in April 2000. Preoperative examination revealed no hematologic abnormality. About sixteen months after the operation, she was readmitted because of pancytopenia with cough and fever. Bone marrow aspiration revealed a very severe hypoplasia in all the three cell lines with over 80% fatty tissue, and chest CT revealed no recurrence of thymoma. Her aplastic anemia had responded to cyclosporine A and granulocyte-colony stimulating factor (G-CSF).

Delayed administration of G-CSF until day +7 after autologous peripheral blood stem cell transplant is as effective in accelerating hematopoietic as day 0

PURPOSE: To compare the hematopoietic recovery and the clinical outcome after high dose chemotherapy and peripheral blood stem cell (PBSC) transplant between patients who received recombinant granulocyte colony-stimulating factor (G-CSF) starting on day 0 and those who received it starting on day +7. PATIENTS AND METHODS: Thirty-five consecutive patients received high dose chemotherapy with ifosfamide, etoposide and carboplatin (ICE) and autologous PBSC transplant. PBSC mobilization was achieved with G-CSF. In 19 transplants done in 1994, G-CSF was started on day 0 and in 16 procedures done in 1995, G-CSF was started on day +7. In both groups G-CSF was given until the absolute neutrophil count was 1 x 10(9)/L. RESULTS: The median number of days to reach an absolute neutrophil count > 0.1 x 10(9)/L, was 11 in the patients who started the G-CSF on day 0 and 11 days in the patients with delayed administration of G-CSF and to reach > 0.5 x 10(9)/L 14 days and 13 respectively. The median number of days to reach a platelet count > 20 x 10(9)/L was 14 and 13. Comparison of early vs. delayed administration of G-CSF did not show any significant differences regarding the time to achieve platelet independence, number of days with fever, median days of hospital stay, number of red cell or platelet transfusions. CONCLUSIONS: Starting G-CSF on day +7 after high dose ICE chemotherapy and autologous transplant of PBSC is as effective in restoring the hematopoietic function as is starting its administration on day 0.

Allogeneic Peripheral Blood Stem Cell Rescue of Late Graft Failure after Bone Marrow Transplantation in Patients with Aplastic Anemia

We investigated the effect and outcome of allogeneic peripheral blood stem cell (PBSC) rescue for aplastic anemia (AA) patients with graft failure after allogeneic bone marrow transplantation (BMT). Seven (28%) of 25 AA patients who received BMT from HLA-identical sibling donors developed late graft failure at a median of 7 months (range, 2.0-9.3 months) after transplantation. The patients with graft failure were treated with PBSC collected from the original donor after mobilization with granulocyte-colony stimulating factor (G-CSF). The median boost dose of peripheral blood mononuclear cells was 3.1 x 10(8)/kg (range, 1.4-11.9 x 10(8)/kg). Median times to reach an absolute neutrophil count greater than 0.5 x 10(9)/L and a platelet count greater than 50 x 10(9)/L were 7 days (range, 4-14 days) and 9 days (range, 3-41 days), respectively. There was sustained graft function in 6 of 7 patients, with a median follow-up duration of 3.3 yr (range, 1.0-6.2 yr). Grade-I acute graft-versus-host disease (GVHD) occurred in 2 patients, while extensive chronic GVHD developed in 3 patients. This report shows that G-CSF-mobilized allogeneic PBSC rescue is very effective in achieving complete and sustained engraftment in patients with AA after graft failure. However, more efficacious measures to prevent extensive chronic GVHD remain to be developed.

Purification of human hemopoietic stem cells for transplantation in Thailand.

Stem cell transplantation (SCT) has become the therapy of choice for many hematologic and immunologic disorders. At present, only 25% of patients have suitable HLA-identical donors. In an attempt to increase the donor pool for SCT in Thailand and Southeast Asia, we developed a program whereby parents and mismatched siblings can be used as donors. In this preliminary study, after granulocyte-colony-stimulating factor (G-CSF) was given to adult donors, peripheral blood stem cells (PBSC) were collected and CD34+ cells purified using a CliniMACS immunomagnetic device (Miltenyi Biotec, Germany). In seven experiments, purified CD34+ cells could be obtained from G-CSF-stimulated PBSC in large numbers (1.71 +/- 0.19 x 10(8)), with high purity (93 +/- 2.4%) and excellent recovery (64.28% - 85.62%). Immune reactive T and NK cells were adequately depleted to less than 0.2%. The purification procedure can be completed within 3 hours. In conclusion, a clinical stem cell purification program using this novel device is now established in Thailand and for the first time in Southeast Asia. This should allow further development of advanced SCT therapy including haploidentical and mismatched CD34+ SCT for patients' lacking HLA-identical donors in this region.