IRIS METASTASIS FROM BREAST CANCER SUCCESSFULLY TREATED WITH ABEMACICLIB AND LETROZOLE.

PURPOSE: To describe a patient with an unusual presentation of iris metastasis from breast cancer and her response to systemic therapy. METHODS: Retrospective chart review of one patient. RESULTS: A 57-year-old woman presented with a superonasal translucent vascularized iris stromal mass with fish egg-like structures budding from the surface. High-frequency anterior segment ultrasonography demonstrated a solid iris stromal mass measuring 6.0 mm × 3.3 mm × 1.9 mm. On optical coherence tomography, the egglike structures appeared as hyperreflective spheres, some of which were detached from the main iris stromal tumor. Oncologic evaluation revealed metastatic breast cancer involving the brain and lung. She was treated with oral abemaciclib and letrozole, as well as external beam radiotherapy to the brain. The iris mass had completely regressed within 4 months and remained undetectable through the 8-month follow-up. The other metastatic lesions responded well to therapy. CONCLUSION: A case of iris metastasis was reported as the presenting sign of cancer dissemination that was successfully treated with targeted systemic therapy without ocular radiotherapy.

A Real-World Data Retrospective Cohort Study of Low Estrogen Receptor-Positive Early Breast Cancer: Natural History and Treatment Outcomes.

Purpose: Estrogen receptor-positive (ER+) breast cancer (BC) is a heterogeneous disease, and there is an ongoing debate regarding the optimal cut point for clinically relevant ER expression. We used a real-world database to assess the prognostic and predictive values of lower ER expression levels on treatment outcomes with endocrine therapy. Methods: We used a nationwide electronic health record database. Descriptive statistics were used to evaluate the association between ER expression, tumor characteristics, and treatment patterns among patients with early-stage BC. We used Kaplan-Meier survival curves to estimate recurrence-free survival (RFS) and overall survival (OS). We assessed associations between an alternative ER expression-level cut point and clinical outcomes. Results: Among 4697 patients with early-stage HER2-negative BC, 83 (2.04%) had ER+-low BC (ER expression, 1-9.99%) and 36 (0.88%) had ER+-intermediate BC (10-19.9%). ER+-low tumors were associated with higher tumor grade, larger size, and higher axillary tumor burden than ER+-high tumors (≥20% ER expression). African Americans had a higher prevalence of both triple-negative BC (TNBC) and ER+-low BC than ER+-high BC. Patients with ER+-low and ER+-intermediate tumors had survival outcomes similar to patients with TNBC and worse survival outcomes than patients with ER+-high tumors (P < 0.001). Tumors with <20% ER expression were associated with worse outcomes. Conclusion: In our cohort, patients with BCs with ER expression levels <20% had poor clinical outcomes similar to those of patients with TNBC.

Real-world benefit of combination palbociclib and endocrine therapy for metastatic breast cancer and correlation with neutropenia.

BACKGROUND: Combination CDK4/6 inhibitor and endocrine therapy has been shown to significantly improve progression-free survival (PFS) in patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (mBC). The aim of this retrospective study was to evaluate the real-world benefit of first-line combination therapy in this cohort and to correlate treatment efficacy with neutropenia, a common toxicity of CDK4/6 inhibitors. METHODS: This study included HR-positive, HER2-negative advanced or mBC patients who were treated with palbociclib plus endocrine therapy, mainly letrozole, between 1 January 2015 and 1 March 2018. Progression-free survival (PFS) was determined using Kaplan-Meier analysis. The predictive value of absolute neutrophil count (ANC) and neutrophil-to-lymphocyte ratio (NLR) for PFS were explored using Cox regression models. Both ANC and NLR were used as a time-dependent variable. RESULTS: In total, 165 patients were included with median PFS of 24.19 months (95% CI 18.93-NR). Median PFS for patients with bone-only metastases (n = 54) was not reached (95% CI 18.21-NR). Among patients with all other metastases (n = 111), median PFS was 24.19 months (95% CI 16.33-33.82). Lower ANC was correlated with decreased risk of progression (HR 0.84, 95% CI 0.71-0.97, p = 0.008). There was no significant association between NLR and the risk of disease progression (HR 1.07, 95% CI 0.97-1.18, p = 0.203). CONCLUSION: The effectiveness of palbociclib and endocrine therapy in the treatment of HR-positive, HER2-negative mBC in the real-world setting is similar to the efficacy reported in the PALOMA-2 trial. Patients with lower neutrophil count may have a lower risk of early disease progression.

Durable Complete Response With Immune Checkpoint Inhibitor in Breast Cancer With High Tumor Mutational Burden and APOBEC Signature.

Increasing data support the importance of preexisting host immune response and neoantigen burden for determining response to immune checkpoint inhibitors (ICIs). In lung cancer and melanoma, tumor mutational burden (TMB) has emerged as an independent biomarker for ICI response. However, the significance of TMB in breast cancer, particularly in the context of PD-L1 negativity, remains unclear. This report describes a patient with HER2-negative breast cancer with high TMB and an apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) trinucleotide signature; her disease was refractory to multiple lines of treatments but achieved durable complete response using ICIs and capecitabine. Additional analysis of the tumor revealed a low amount of stromal tumor-infiltrating lymphocytes (sTILs) and PD-L1 negativity, reflecting a poor preexisting host immune response. In collaboration with Foundation Medicine, comprehensive genomic profiling from 14,867 patients with breast cancer with the FoundationOne test was evaluated. Using the cutoff of ≥10 mutations/megabase (mut/Mb) for high TMB, PD-L1 positivity and TMB-high populations were not significantly overlapping (odds ratio, 1.02; P=.87). Up to 79% of TMB-high tumors with >20 mut/Mb were PD-L1-negative. Our study highlights that despite having low TILs and PD-L1 negativity, some patients may still experience response to ICIs.

Effects of Age and Immune Landscape on Outcome in HER2-Positive Breast Cancer in the NCCTG N9831 (Alliance) and NSABP B-31 (NRG) Trials.

PURPOSE: Young age has been shown to be an independent predictor of poor outcome in breast cancer. In HER2-positive breast cancer, the effects of aging remain largely unknown. EXPERIMENTAL DESIGN: A total of 4,547 patients were included [3,132 from North Central Cancer Treatment Group (NCCTG) N9831 and 1,415 from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31]. Pathologic stromal tumor-infiltrating lymphocyte (sTIL) and molecular tumor infiltrating lymphocyte (mTIL) signatures were evaluated. RESULTS: In NCCTG N9831, comparable benefit of trastuzumab was observed in all patients [age ≤ 40; HR, 0.43; 95% confidence interval (CI), 0.28-0.66; P < 0.001; and age > 40; HR, 0.56; 95% CI, 0.45-0.69; P < 0.001]. Similar results were observed in NSABP B-31 (age ≤ 40; HR, 0.45; 95% CI, 0.29-0.68; P < 0.001; and age > 40; HR, 0.42; 95% CI, 0.33-0.54; P < 0.001). Among patients who received chemotherapy alone, younger age was associated with poor outcome in the hormone receptor-positive subset, but not the hormone receptor-negative subset, in both trials. Although there was no association between sTILs and age, a small, but significant increase in mTIL CD45 and some immune subset signatures were observed. Among patients who received chemotherapy alone, patients over 40 years of age with lymphocyte-predominant breast cancer had excellent outcome, with 95% remaining recurrence free at 15 years. CONCLUSIONS: Among patients treated with trastuzumab, there was no significant difference in outcome related to age. Our study suggests that trastuzumab can negate the poor prognosis associated with young age.

Valor pronóstico de las isoenzimas de LDH en pacientes con linforma no hodgkin / Prognostic value of LDH isoenzymes in patients with non-Hodgkin linforma

La enzima lactato deshidrogenasa (LDH) es un factor pronóstico en Linfoma No Hodgkin (LNH). El objetivo del trabajo consistió en evaluar prospectivamente el valor pronóstico de las isoenzimas de LDH en pacientes con LNH. Se estudiaron 67 pacientes de primera consulta con diagnóstico de LNH, sin tratamiento previo, VIH negativo y sin otras enfermedades, tiempo promedio de seguimiento 30 meses (rango 3-48 meses). Las muestras de suero se recolectaron previas al tratamiento. La LDH total (LDHT) e isoenzimas de LDH se determinaron respectivamente por método cinético y electroforesis de proteínas en gel de agarosa. Se procesaron muestras de 122 controles sanos para establecer los valores de referencia de las isoenzimas de LDH. 49(73%) LNH agresivos y 18(27%) LNH indolentes y según el Índice Pronóstico Internacional (IPI), 60 (90%) bajo riesgo y 7(10%) alto riesgo. Las isoenzimas LDH1, LDH2, LDH3, LDH4 y LDH5 presentaron niveles absolutos significativamente elevados en 25 (37%), 29 (43%), 32 (48%), 20 (39%) y 11 (16%) de los casos respectivamente (p<0,0001). La actividad porcentual de LDH4 en los pacientes con LNH agresivos fue significativamente superior respecto al grupo de LNH indolentes (p=0,01). En el análisis univariado, valores absolutos elevados de LDH1 se asociaron significativamente con una sobrevida global disminuida (p=0,0064) en el grupo total de pacientes. LDH1 conservó su valor pronóstico aún en el grupo de pacientes con valores normales de LDHT (p=0,04). En pacientes con LNH agresivos, valores elevados de LDHT e IPI alto riesgo se asociaron significativamente con una menor sobrevida global (p<0,05). En el análisis multivariado la LDHT e IPI resultaron factores pronósticos independientes de la sobrevida. Alteraciones específicas del patrón de isoenzimas de LDH sugieren la relación de LDH4 con la biología del tumor y su actividad proliferativa en LNH agresivos y el valor pronóstico de LDH1 como factor adverso de la sobrevida en el análisis univariado.

Lactate dehydrogenase (LDH) is a prognostic factor in non-Hodgkin lymphoma (NHL). Our objective was to evaluate prospectively the prognostic value of LDH isoenzymes in patients with NHL. We studied 67 newly diagnosed NHL patients, previously untreated, HIV-negative and free from other disease, median follow-up of 30 month (range 3-48 month). Before starting treatment serum samples were collected for the determination of total LDH (LDHT) and LDH isoenzymes that were respectively assayed by kinetic method and protein electrophoresis in agarose gel. In order to set reference values of LDH isoenzymes samples from122 healthy controls were processed. Results: 49(73%) of the patients were aggressive NHL and 18(27%) indolent NHL and according to the International Prognostic Index (IPI), 60(90 %) low risk and 7(10%) high risk. High absolute values of LDH1, LDH2, LDH3, LDH4 and LDH5 isoenzymes were significantly elevated in 25 (37%), 29 (43%), 32 (48%), 20 (39%) and 11 (16%) of cases respectively (p<0,0001). The percentage value of LDH4 activity in aggressive NHL patients was significantly higher compared to indolent NHL group (p=0,01). In univariate analysis increased LDH1 absolute values were significantly associated with decreased overall survival in the total group of patients (p = 0.0064). LDH1 remained a prognostic factor for survival even when considering the group of patients with normal serum LDHT values (p = 0.04). In patients with aggressive NHL increased values of LDHT and high risk IPI were significantly associated with decreased overall survival (p<0.05). In a multivariate analysis LDHT and IPI score were independent prognostic factor for survival.

Unexpectedly high frequency of European parentage in Venezuelan patients with chronic lymphocytic leukemia.

There is insufficient information on the characteristics of chronic lymphocytic leukemia (CLL) in Latin American patients. Immunoglobulin variable-region heavy-chain (IGVH) gene usage and mutation status and prognostic factors were investigated in patients resident in Venezuela. The most frequently used IGVH family genes were: VH3 > VH1 > VH4 > VH5, with a high incidence of IGVH1.69 and IGVH3.21 genes, and 55.2% of IGVH genes were mutated. Analysis of HCDR3 (third complementarity-determining region of the heavy chain) revealed that 24% of Venezuelan HCDR3s belonged to a CLL stereotyped HCDR3. Results for prognostic factors were similar to those reported previously for Caucasian populations. Interestingly, we found an over-representation of people of European extraction among Venezuelan patients with CLL, suggesting the possibility of a higher frequency of susceptibility genes for CLL in Europeans in comparison with Latin American mestizos.

Perfil de las isoenzimas de LDH en linfoma no Hodgkin: correlación con marcadores tumorales / Profiles of LDH isoenzymes in non-Hodking`s lymphoma: correlation with tumor markers

Lactate dehydrogenase (LDH) consists of five isoenzymes and is an important prognostic factor in non-Hodgkin’s lymphoma (NHL) patients. Our objective was to study the pattern of LDH isoenzymes in patients with NHL and its correlation with clinical pathological and biological tumor markers. We evaluated 67 newly diagnosed NHL patients clinically and histologically confirmed, previously untreated, HIV-negative and free from other diseases, during the period 1999-2004, the average follow-up time of 30 months (range 3-48), median age of 55 years (range 18-79), the International Prognostic Index (IPI ) 60 (90%) of low risk and 7 (10%) of high risk. Serum and whole blood samples were collected for the determination of LDH, LDH isoenzymes, enzymes (AST, ALT, phosphatase alkaline), Beta 2 Microglobulin, CA125, and IL-6, sRáIL-2, C Reactive protein, serum albumin and ESR. Serum samples were processed from healthy controls in order to set reference values of LDH isoenzymes. Serum levels of LDH and absolute values of LDH isoenzymes were significantly higher in patients compared to controls (p<0.001). Frequencies of high absolute values of LDH1, LDH2, LDH3, LDH4 and LDH5 isoenzymes were significantly elevated in 25 (37%), 29 (43%), 32 (48%), 20 (39%) and 11 (16%) of cases, respectively. LDH1 activity associated and correlated with adverse clinical pathological, biological factors and high risk IPI, suggets that it is an indicator of cell turnover and disease activity. LDH2 changes reflected its association and correlation with clinical pathological and biological factors which are indicators of disease progression, tumor proliferative activity, adverse IPI and the patient’s response to the illness. LDH3 was elevated with greater frecuency and its activity was associated with clinical pathological and biological prognostic factors reflecting the patient’s response against the tumor, as well as inflammatory activity and disease extension...

La enzima lactato deshidrogenasa (LDH) está conformada por cinco isoenzimas y es un importante factor pronóstico en pacientes con Linfoma No Hodgkin (LNH). Nuestro objetivo fue estudiar el patrón de las isoenzimas de LDH en pacientes con LNH y su correlación con marcadores tumorales clínico-patológicos y biológicos. Se evaluaron 67 pacientes de primera consulta con diagnóstico de LNH confirmados clínica e histopatológicamente, sin tratamientos previo, VHI negativo y sin presentar otras enfermedades, durante el período 1999-2004, siendo el tiempo promedio de seguimiento de 30 meses (rango 3-48 meses), edad promedio 55 años (rango 18-79), Índice Pronóstico Internacional (IPI) 60 (90 por ciento) bajo riesgo y 7 (10 por ciento) alto riesgo. Se recolectaron muestras de sangre, para la obtención de suero y sangre total para la determinación de LDH, Isoenzimas de LDH, enzimas (AST, ALT, fosfatasa alcalina), Beta 2 Microglobulina, CA125,IL-6,sRIL-2, Proteína C Reactiva, Albúmina sérica y VSG. Se procesaron muestras de suero de controles sanos para establecer los valores de referencia de las isoenzimas de LDH. Los nieveles séricos de la LDH y los valores absolutos de las isoenzimas de LDH fueron significativamente superiores en los pacientes respecto al grupo control (p<0,001). Las frecuencias de las isoenzimas LDH1, LDH2, LDH3, LDH4 y LDH5 resultaron con niveles absolutos significativamente elevados en 25 (37 por ciento), 29 (43 por ciento), 32 (48 por ciento), 20 (39 por ciento) y 11 (16 por ciento) de los casos respectivamente. La asociación y correlación de la actividad de LDH1 con los factores clínico-patológicos adversos, IPI alto riesgo y marcadores biológicos alterados , sugieren su expresión como un indicador de recambio celular y actividad de la enfermedad. Los cambios en el patrón de la LDH2 reflejaron su asociación y correlación con factores clínico-patológico y biológicos indicadores de la pregresión de la enfermedad...

Clinical bioequivalence of a dose of clopidogrel Leti Cravid tablets 75 mg versus clopidogrel Sanofi Plavix tablets 75 mg administered on a daily dose for 7 days on healthy volunteers: a clinical trial.

Patients undergoing percutaneous coronary intervention procedures, as in patients with coronary disease, should receive treatment indefinitely with acetylsalicylic acid and clopidogrel. New brands of clopidogrel have been developed at lower costs, for helping to avoid premature suspension of antiplatelet therapy, as Cravid Leti Laboratories clopidogrel. Its effectiveness and safety must be compared with Plavix international standard. A prospective, comparative, cross-over, and randomized study was conducted in healthy volunteers. Each group received 1 tablet of Clopidogrel Leti or Clopidogrel Sanofi, 75 mg in a single dose daily for 7 days, followed by 7-day washout period before administration of second treatment. Platelet aggregation was measured at the start of each period and at 7 days of treatment through optical aggregometry, using an optical aggregometer 490-2D Chrono-Log, with a self-calibration system working with platelet-rich plasma with readings 0%-100% of light transmission. An important decrease of platelet aggregation was observed in both groups at 7 days of treatment of more than 50%, independent of adenosine diphosphate reactive (Helena and Chrono-Log) used for aggregation (P < 0.05). The relationship between the mean and 90% confidence interval ratio obtained with the 2 different adenosine diphosphate brands were between 80% and 125%, therefore, it can be considered that both brands are bioequivalent and perfectly exchangeable.

Valor pronóstico de los niveles séricos del CA-125 en pacientes con linfoma no hodgkin / Prognostic value of serum CA 125 levels in non-hodgkin's lymphoma patients

El CA 125 ha sido considerado un nuevo marcador pronóstico en linfoma No Hodgkin (LNH). El objetivo del trabajo consistió en evaluar la significancia pronostica de los niveles del CA 125 en pacientes con LNH, asociación y correlación con factores clínicos patológicos, biológicos y sobrevida. Se procesaron muestras de suero de 67 pacientes con diagnóstico de LNH, de primera consulta, pretratamiento, VIH negativo y sin presentar otras enfermedades, edad promedio 55 años (rango 18-79 años), LNH agresivos 49 (73%) y LNH indolentes 18 (27%), IPI 60 (90%) de bajo riesgo y 7 (10%) de alto riesgo, tiempo promedio de seguimiento 30 meses (rango 3-48 meses). CA 125, B2M e IL-6 se determinaron por inmunoensayos enzimáticos y Proteína C Reactiva, Albúmina sérica, LDH, AST, ALT y fosfatasa alcalina por métodos de aglutinación directa, colorimétrico y cinético, respectivamente. 16 (24%) de los pacientes expresaron niveles elevados de CA 125 (>35u/ml) (p<0,001). Asociación significativa (p≤0,05) de CA 125 (35u/ml) con estadío clínico (EC) III-IV, enfermedad voluminosa (EV)>10cm, síntomas B (SB), enfermedad abdominal (EAb) y níveles elevados de LDH y B2M. Correlación significativa y directa con EC, EV, SB, LDH, B2M y AST (p≤0,05) y correlación inversa con albúmina sérica (p=0,02). El análisis univariado mostró una significativa disminución de la sobrevida global en los pacientes con LNH agresivos y niveles elevados de CA 125(>35u/ml) (p=0,03), LDH (p=0,048) y B2M(p=0,02). Según el análisis multivariado, Ca 125 perdió su significancia, LDH (p=0,04) y B2M (p=0,003) mantuvieron su valor pronóstico independiente. Los resultados del presente trabajo sugieren la utilidad pronóstica de los niveles séricos del CA 125, siendo recomendable su inclusión en la evaluación clínica inicial e los pacienten con LNH.

CA 125 has been considered a new prognostic marker in Non-Hodgkin lymphoma (NHL). The objetive of this study was to determine the prognostic significance of CA 125 levels in NHL patients, the association and correlation with clinical pathological and biological factos and survival. We processed 67 serum samples from newly diagnosed NHL patients previously untreated, HIV-negative and free from other diseases, mean age 55 years (range 18-79 Years), agressive NHL 49 (73%) and indolent NHL 18 (27%), IPI: 60 (90%) of low risk and 7 (10%) high risk, the average time of follow up was 30 months (range 3-48 months). CA 125, B2M and IL-6 were determined by enzyme immunoassay methods. C-reactive protein, serum albumin, LDH, AST, ALT and alkaline phosphatase were determined by direct agglutination, colorimetric and kinetic methods, respectively. Elevted levels of CA 125 (>35u/ml) were expressed in 16 (24%) of the patients (p<0.001). CA 125 levels (>35u/ml) were significantly (p≥0.05) associated with the follwing factors: clinicals stage (CS) III-IV, bulky disease (BD)>10 cm, B symptoms (BS), abdominal disease (ABD) and elevated levels of LDH and B2M. There was a significant and direct correlation (p≤0.05) with CS, BD, BS, LDH, B2M and AST and inversely with serum albumin (p=0,02). Univariate analysis showed a significant decreased of overall survival in patients with aggressive NHL with elevated levels of CA 125 (p<0.048), LDH (p=0.048) and B2M (p=0,02). In multivariate analysis Ca 125 lost its prognostic significance, LDH (p=0.04) and B2M (p=0.003) remained their independent prognostic value. The results of this study suggest the prognostic value of serum levels of CA 125, being recommended for inclusion in the initial clinical evaluation of patients with NHI.

Hemopoietic progenitor cell identification in fetal and adult blood / Célula progenitora hamatopoética: identificação em sangue fetal e de adulto

Hemopoietic progenitor cells give rise to all cellular elements of the blood and are of importance as a potential source of cells used for correction of various pathological conditions. The main objective of this study was to identify and quantitative hemopoietic progenitor cell in antenatal fetal blood, in cord blood at the time of delivery and in adult blood, using monoclonal antibodies to surface markers and flow cytometry. CD34+ cells, most of them probably representing progenitor cells, were detected in prenatal fetal blood as early as the 17th week of gestation. The proportion of these cells showed a tendency to decrease as the pregnancy progressed. Within the population of CD34+ cells, a relatively low proportion (less than 1 percent) were negative for the surface marker CD33 or HLA-Dr, indicating a population of primitive stem cells, i.e., progenitor cells no committed to a specific lineage. On the contrary, another group coexpressed CD33 or HLA-Dr, being more mature progenitor cells already committed to differentiate along a specific lineage. The percentage of CD34+ obtained in blood of adult patients after mobilization with chemotherapeutic agents and growth factors showed an average value of 2.7± 3.1 percent. The percentage of CD34+ in the apheresis products of various patients varied from 0.58 to 1.48. In some cases the cells were reinfused in the patient with good results. Our findings are in agreement with previous studies suggesting that CD34+ stem cells is a heterogeneous population, with each subset having variable degree o commitment to differentiate toward a specific cell lineage.

As células progenitoras hematopoéticas são as responsáveis pela produção de todos os elementos do sangue e são as potenciais fontes de células usadas para o tratamento de várias condições patológicas. O principal objetivo deste trabalho foi identificar e quantificar as células progenitoras hematopoiéticas no sangue fetal do período pré-natal, no sangue de cordão umbilical no momento do parto e no sangue do adulto, usando anticorpos monoclonais para marcadores de superfície e citometria de fluxo. As células CD34+ na maioria das vezes representam células progenitoras e foram detectadas no sangue fetal pré-natal tão precoce como na 17ª semana de gestação. A proporção destas células mostrou a tendência de diminuir durante a progressão da gestação. Dentro da população de células CD34+, uma proporção relativamente pequena (menos de 1 por cento) foi negativa para os marcadores de superfície CD33 ou HLA-Dr, indicando uma população de células primitivas, isto é, células progenitoras não comissionadas com uma linhagem específica. Ao contrário, outro grupo co-expressa CD33 ou HLA-Dr, sendo progenitores celulares mais maduros já comprometidos com linhagens específicas. A porcentagem de CD34+ obtida no sangue de adultos após mobilização com agentes quimioterápicos e fator de crescimento mostrou uma média de 2.7+/-3.1 por cento. 0 por cento de CD34+ no produto aferético de vários pacientes variou de 0.58 a 1.48. Em alguns casos as células foram infundidas nos pacientes com bons resultados. Nossos achados estão de acordo com estudos prévios sugerindo que células CD34+ sejam uma população heterogênea com cada subgrupo apresentando graus de comprometimento com diferentes linhagens específicas.

Haemostatic changes related to fibrin formation and fibrinolysis during the first trimester in normal pregnancy and in recurrent miscarriage.

We have studied some biophysical properties of the fibrin network during the normal state of pregnancy and in patients with recurrent miscarriage (RM), in the first trimester of pregnancy. The fibrin polymerization process, followed by turbidity, showed that the rate of fibrin monomer assembly and the final turbidity was increased in the pregnant group (normal and with history of RM) compared to non-pregnant women (normal and RM), which is consistent with the increased fibrinogen concentration during pregnancy. No changes were observed in the Darcy constant (Ks) of RM clots, pregnant or not; however, in pregnant control subjects the Ks increased (p = 0.03). The fibrin lysis rate was increased in pregnant women compared to non-pregnant, being faster in women with RM. The rheological properties of the fibrin network in the non-pregnant group (control and RM patients) were similar; in the pregnant state, the fibrin network of the control group was 1.3 times stiffer compared to the control non-pregnant women, and almost unchanged in RM patients. In this study we have found changes in the clot structure that seem to be related to normal pregnancy and an increased rate of the fibrin lysis process in the RM patients, which may have clinical relevance.

Valor pronóstico de los niveles séricos del receptor a soluble de interleuquina-2 en pacientes con linfoma No Hodgkin / Prognostic value of serum soluble interleukin-2 a receptor levels in Non Hodgkins lymphoma patients

El receptor a soluble de la interleuquina 2 (sRaIL-2) ha sido considerado un marcador pronóstico en pacientes con linfoma No Hodgkin (LNH). El objetivo del trabajo consistió en determinar la significancia de los niveles del sRaIL-2 en pacientes con LNH, su correlación con factores clínico patológicos, biológicos y su valor pronóstico. Se procesaron muestras de suero de 43 nuevos casos de pacientes con LNH, pretratamiento, edades comprendidas entre 25-84 años, mediana 55 años, 33 (77%) LNH agresivos y 10 (23%) LNH indolentes. Según el Índice Pronóstico Internacional (IPI), 37 (86%) de bajo riesgo y 6 (14%) de alto riesgo, siendo el tiempo promedio de seguimiento de la enfermedad 30 meses (rango 3-48 meses). Se recolectaron 20 muestras de suero de controles sanos, donantes de banco de sangre, para determinar el valor de referencia. Las muestras de pacientes y controles se congelaron a -70ºC hasta su procesamiento. El sRaIL-2 se determinó por un inmunoensayo enzimático adsorbente (ELISA), sensibilidad 10 pg/ml y se consideraron elevados los niveles >2000 pg/ml. Los marcadores biológicos: Beta 2 microglobulina (B2M), Proteína C Reactiva (PCR), Velocidad de sedimentación globular (VSG), Albúmina sérica, Lactato deshidrogenasa (LDH), Aspartato amino transferasa (AST), Alanino amino transferasa (ALT) y Fosfatasa alcalina (ALP), se determinaron por métodos de inmunoensayo enzimático sobre micropartículas (MEIA), aglutinación directa, Wintrobe, colorimétrico y cinético, respectivamente. Los niveles séricos del sRaIL-2 en pacientes con LNH fueron significativamente superiores al del grupo control (p <0,001) y 26 (60%) de los pacientes expresaron niveles elevados del sRaIL-2 (p< 0,001). Se detectaron niveles del sRaIL-2 significativamente incrementados asociados a pacientes con estadio clínico (EC) III-IV (p= 0,02), síntomas B (p= 0,04), valores elevados de B2M (p= 0,01) y PCR (p= 0,05)...

Soluble Interleukin–2 a receptor (sIL-2aR) has been considered as a prognostic marker in Non-Hodgkin’s lymphoma (NHL) patients. The aim of this study was to assess the significance of sIL-2aR levels in the pre-treatment serum of NHL patients, as well as its correlation with the clinical-pathological and biological factors and its prognostic value. Forthy-three serum samples from newly diagnosed NHL patients were processed before starting the treatment. The median age was 55 years old (range 25-84 years), 33 cases (77%) were classified as aggressive lymphomas and 10 cases (23%) as indolent lymphomas. According to the International Prognostic Index (IPI), 37 cases (87%) were classified as high risk group and 6 cases (14%) as low risk group. The average time of follow–ups was 30 months (range 3-48 months). 20 healthy control samples from blood bank donors were collected for establishing the reference value. All patients and control samples were kept at -70ºC until processed. The sIL-2aR levels were determined by applying an enzyme-linked immunosorbent assay (ELISA), sensitivity 10 pg/ml. Values were considered elevated when they exceeded 2000 pg/ml. The biological markers: Beta 2 microglobulin (B2M), C-Reactive Protein (CRP), erythrocyte sedimentation rate (ESR), serum albumin, serum lactate dehydrogenase (LDH), aspartate amino transaminase (AST), alanine amino transaminase (ALT), alkaline phosphatase (ALP), were determined by the methods of microparticle enzyme immunoassay (MEIA), direct agglutination, Wintrobe, colorimetric and kinetic respectively. The sIL-2aR serum levels in the NHL patients were significantly higher than the control group (p< 0.001) and 26 (60%) of the patients expressed values higher than 2000 pg/ml (p<0.001). Significantly elevated serum levels of sIL-2aR were associated with clinical stage (CS) III-IV (p= 0.02), B symptoms (p= 0.04), elevated levels of B2M (p=0.01) and CRP (p=0.05)...

Tratamiento de la enfermedad de hodgkin: esquema MOPP/ABV toxicidad (2a neoplasia): seguimiento durante 10 años / Treatment of the Hodgkin`s disease: scheme MOPP/ABV toxicity (2 neoplasms) follow-up for 10 years

Determinar la eficacia de un régimen híbrido de siete drogas en pacientes con enfermedad de Hodgkin en estadios avanzados y en estadios tempranos II-B con factores pronósticos desfavorables. Entre enero de 1988 y diciembre de 1998 fueron tratados 126 pacientes, (edad promedio: 33 años), y un seguimiento promedio de 5,6 años. Los estadios clínicos fueron II-B en 42 pacientes (33 por ciento), estadio III en 55 pacientes (44 por ciento), y estadio IV en 29 pacientes (23 por ciento). Los factores pronósticos (FP) evaluados fueron: edad> 45 años, sexo masculino, síntomas B, MM > 30 por ciento, EC IV y VSG> 50 mm 1° hora. Todos recibieron 6 ciclos de quimioterapia (MOPP/ABV). Ciento siete pacientes (84 por ciento) obtuvieron remisión completa; remisión parcial en 16 (13 por ciento); progresaron al final del tratamiento en 3 (3 por ciento); y 13/107 (12 por ciento) recayeron. La tasa de sobrevida total y la tasa de sobrevida libre de falla de todo el grupo a los 10 años fueron de 76 por ciento y 62 por ciento, respectivamente. La toxicidad hematológica aguda incluyó neutropenia, trombocitopenia y anemia. La toxicidad tardía fue de nódulo tiroideo de 4 por ciento leucemia mieloide aguda en 3 por ciento afectación cardíaca en 1,6 por ciento y tumor sólido (esófago) en 0,8 por ciento. Las tasas de incidencia fueron altas para segundo tumor, cáncer de esófago y leucemia secundaria. Por lo que, a pesar de los resultados obtenidos debimos descontinuar el uso de esta combinación