Abstract Objective: Our objective was to evaluate the frequency of expression and determine the expression levels of the NY-ESO-1 gene in patients with DLBCL as well as to examine its relationship with clinical parameters and survival. Methods: We analyzed NY-ESO-1 gene expression levels using real-time quantitative RT-PCR (RT-qPCR) in 112 patients with DLBCL. The associations between the expression of the NY-ESO-1 gene and the clinical variables were evaluated using the Chi-square test and Fisher’s exact test. Overall survival (OS) was determined using the Kaplan–Meier method. Result: The results showed that the NY-ESO-1 gene was expressed in 46.4% (52/112) of patients with DLBCL, and NY-ESO-1 gene expression was associated with clinical parameters such as LDH, clinical stage, and International Prognostic Index (IPI) (p ≤ 0.05). High levels of NY-ESO-1 gene expression were associated with advanced disease stages, and the survival rates after 5.3 years of tracking were lower in the patients expressing the NY-ESO-1 gene (66.4%) than in those not expressing the gene (23.1%). Conclusion: The expression levels of the NY-ESO-1 gene in patients with DLBCL may be of great utility for diagnosing and determining the prognosis of this disease.

Abstract Cancer is a significant cause of death worldwide. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is spreading rapidly globally. Information on coronavirus disease 2019 (COVID-19) and its complications in cancer patients are still limited. It is relevant to consider that some chemotherapeutic agents have secondary immunosuppressive effects. Approximately 35% of hematologic cancer patients develop pneumonia caused by community respiratory viruses. People older than 65 years-old or with severe neutropenia or lymphopenia are at higher risk. Cancer patients with pneumonia infected by parainfluenza virus showed a higher risk of mortality compared to non-cancer patients (p < 0.05; 12.3% vs. 3.8%) or coronavirus infections (p < 0.01; 24% vs. 30%). Complications associated with SARS-COV2 infection in cancer patients are limited to descriptive studies, with those who received myeloablative, immunosuppressive or monoclonal antibody therapies being more susceptible.

Resumen El cáncer es una causa significativa de muerte en todo el mundo. La infección por el síndrome respiratorio agudo severo coronavirus-2 (SARS-CoV-2) se está propagando rápidamente a nivel mundial. La información sobre la enfermedad por coronavirus 2019 (COVID-19) y sus complicaciones en pacientes con cáncer aun es limitada. Es relevante considerar que algunos agentes quimioterapéuticos tienen efectos inmunosupresores secundarios. Aproximadamente el 35% de los pacientes con cáncer hematológico desarrolla neumonía causada por virus respiratorios comunitarios. Las personas mayores de 65 años o con neutropenia o linfopenia grave tienen un mayor riesgo. Los pacientes oncológicos con neumonía infectados por el virus parainfluenza mostraron un mayor riesgo de mortalidad en comparación con los pacientes no oncológicos (p < 0.05; 12.3% vs. 3.8%) o infectados por coronavirus (p < 0.01; 24% vs. 30%). Las complicaciones asociadas con la infección por SARS-COV2 en pacientes con cáncer se limitan a estudios descriptivos, siendo más susceptibles aquellos que recibieron terapias mieloablativas, inmunosupresoras o con anticuerpos monoclonales.

Resumen El mieloma múltiple (MM) es una neoplasia originada de células B, secundaria a diversas mutaciones post-germinales y cuya característica es el desarrollo de una clona de células plasmáticas que secretan un subtipo específico de inmunoglobulina conocido como el componente monoclonal. Dentro de las manifestaciones clínicas más comunes se encuentran tanto la anemia, la enfermedad renal y las lesiones óseas, pero cada vez son más los casos que muestran al diagnóstico manifestaciones clínicas atípicas que pueden influir con el pronóstico y con la calidad de vida. Debido a que el tratamiento moderno del MM es altamente prometedor, es necesario identificar aquellas condiciones clínicas que limitan la eficacia terapéutica.

Abstract Germ cell tumors (GCT) are the most common malignant neoplasms affecting young men aged 15 to 35 years. Patients with Multiple myeloma (MM) is a B-cell neoplasm secondary to various post-germline mutations, characterized by the development of a clone of plasma cells that secrete a specific subtype of immunoglobulin known as the monoclonal component. Anemia, kidney disease, and bone lesions are among the most common clinical manifestations. However, cases showing atypical clinical manifestations that can influence prognosis and quality of life are becoming increasingly frequent. Given that modern MM treatment is highly promising, it is necessary to identify those clinical conditions that limit therapeutic efficacy.

Abstract Introduction: Various biomarkers based on blood counts have been useful for the prognosis of patients critically ill with COVID-19. Objective: To describe the usefulness of the neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR) and lymphocyte-to-platelet ([LPR) ratios for the prognosis of mortality and ventilatory support requirement for COVID-19. Method: Retrospective cohort of clinical records of patients with COVID-19 who required hospital care. Results: One-hundred and twenty-five cases were analyzed; mean age was 51 years, and 60 % were of the male gender; 21.6 % had type 2 diabetes mellitus, and 18.4 % had hypertension. Mean leukocyte count was 9.5 × 103/mL, with a neutrophil mean of 8.0 × 103/mL. Mean NLR was 12.01, while for MLR it was 0.442, and for LPR, 373.07. Regarding the area under the curve, the following values were recorded for mortality: 0.594 for NLR, 0.628 for MLR and 0.505 for LPR; as for mechanical ventilation, the values were 0.581 for NLR, 0.619 for MLR and 0.547 for LPR. In the univariate analysis, an NLR value > 13 (OR: 2.750, p = 0.001) and an MLR of > 0.5 (OR: 2.069, p = 0.047) were associated with mortality. LPR showed no impact on mortality or respiratory support. Conclusion: NLR and MLR are useful for predicting mortality in patients with COVID-19.

Resumen Introducción: Diversos biomarcadores basados en conteos sanguíneos han sido de utilidad para el pronóstico de los pacientes en estado crítico por COVID-19. Objetivo: Describir la utilidad de los índices neutrófilo/linfocito (INL), monocito/linfocito (IML) y linfocito/plaqueta (IPL) para el pronóstico de la mortalidad y necesidad de soporte ventilatorio por COVID-19. Método: Cohorte retrospectiva de registros clínicos de pacientes con COVID-19 que requirieron atención hospitalaria. Resultados: Se analizaron 125 casos, la edad media fue de 51 años y 60 %, del sexo masculino; 21.6 % padecía diabetes mellitus tipo 2 y 18.4 %, hipertensión. La media de leucocitos fue 9.5 × 103/mL y la de neutrófilos, de 8.0 × 103/mL. La media del INL fue de 12.01; del IML, de 0.442 y del IPL, de 373.07. Respecto al área bajo la curva se registraron los siguientes valores en cuanto a mortalidad: INL, 0.594; IML, 0.628 e ILP, 0.505; en cuanto a ventilación mecánica: INL, 0.581; IML, 0.619 e ILP, 0.547. En el análisis univariado, INL > 13 (RM = 2.750, p = 0.001) e IML > 0.5 (RM = 2.069, p = 0.047) se asociaron a mortalidad; ILP no mostró impacto en la mortalidad ni en el soporte respiratorio. Conclusión: INL e IML son de utilidad para predecir la mortalidad en pacientes con COVID-19.

Background: The osmotic fragility (OF) test is one of the most suitable procedures to determine the resistance of the erythrocyte membrane under conditions of osmotic stress. One of the most frequent clinical uses of the FO test is the diagnosis of hereditary conditions that affect erythrocytes: thalassemia and spherocytosis. Both conditions induce red blood cells (RBCs) to be prone to swelling and then lyse under osmotic stress faster than those RBCs without any pathology. Since the standard OF test is time consuming and needs specialized equipment, a fast, accessible, and reliable technique is necessary to determine the OF. Objective: The objective of the study was to evaluate an alternative technique to determine the OF of erythrocytes by refractive index (RI) measurements. The method consists of measuring the real part of the RI of dilutions of whole blood samples with hypotonic solutions at different NaCl concentrations, ranging from 0% to 0.9% using a standard Abbe refractometer. Materials and methods: An experimental study was carried out with volunteers who went to the General Hospital of Mexico "Eduardo Liceaga." Peripheral blood samples from 12 healthy volunteers were used through the standard blood draw procedure and stored in a heparinized vacutainer tube. Results and conclusions: The proposed technique that uses an Abbe refractometer to measure the infrared of different solutions of whole blood and hypotonic solutions to determine the OF curve has proven to be simpler and more robust than the standard method based on the measurement of light absorption in dilutions of hemolyzed blood. The determination of the OF of erythrocytes rapidly and straightforwardly can be useful in the detection of specific pathologies.

Background: The use of all-transretinoic acid together with chemotherapy has improved the prognosis of patients with acute promyelocytic leukemia (APL). However, less than 20% still die prematurely, mainly from hemorrhage. Objective: The objective of this study was to identify the utility of the PETHEMA score and complete blood count (CBC) score for the detection of patients with APL at risk of premature death. Materials and methods: A retrospective observational study in patients with de novo APL treated between 2001 and 2015 at Hospital General de México. Results: Among the 79 patients studied, the mean age was 35 years (17-57 years). According to the PETHEMA score, most patients were deemed low risk (n = 34, 42.5%) followed by high-risk (n = 25, 31%) and intermediate-risk patients (n = 21, 26.3%). As per the CBC score, 16.3% (n = 13), 31.3% (n = 25) and 52.5% of patients (n = 42) were considered as low-risk (0 points), intermediate-risk (1 and 2 points), and high-risk patients, respectively (3 points). Overall survival at 5 years was 73%, with a lower rate in those patients considered as high risk for the two scales. Individually, both thrombocytopenia and elevated fibrinogen levels were associated with premature death. Conclusion: The PETHEMA score, like the CBC score, allows for the identification of patients at risk of premature death, with as thrombocytopenia is an independent risk factor.

Background: Metformin has antineoplastic and cancer protective effects in vitro, sensitizing leukemia cells to chemotherapeutic agents, inducing apoptosis and cell cycle arrest. Aim: To assess the effect of metformin on the induction stage in patients with ALL and its impact on overall survival and relapse. Material and Methods. We included 123 patients treated with metformin and without metformin. The dose used was 850 mg PO at 8 h intervals. The survival analysis was used by Kaplan-Meier method, the difference between the distinct groups was performed using the log Rank test. Results. The overall survival at a median follow up of 700 days of follow-up was 43%, with a disease-free survival of 47%. Regarding the treatment groups, patients with metformin had a lower rate of relapse compared to the group receiving only chemotherapy (6.5% vs 17.1%, p = 0.006). Conclusions. The addition of metformin to the conventional treatment of ALL was associated with an improvement in survival, this association being independent of the type of biological risk at diagnosis.

Objetivos: Identificar aquellos factores que impactan en la respuesta terapéutica para alcanzar una segunda remisión (2 RC) en pacientes con leucemia aguda linfobl´stica (LAL) en recaída. Métodos: Estudio observacional y analítico anidado en una cohorte retrospectiva de adultos (>18 años) portadores de LAL que fueron atendidos durante 2008-2014 y que interrumpieron el protocolo HGMLAL07 al detectarse recaída e iniciaron otro esquema. Resultados: Se estudiaron 69 pacientes y el 62,3% (n = 43) correspondía a hombres. La media de edad fue de 29 años. Los regímenes terapéuticos empleados fueron: alta intensidad (55,1%) [Hyper-CVAD (n = 34), IDA-Flag (n = 1), mitoxantrona-DARAC (n = 3) ], moderada intensidad (4,3%) [Esquemas de reinducción (n = 3) ] y tratamiento paliativo de baja intensidad con soporte transfusional (40,6%, n = 28). Solo 19 pacientes (27,5%) integraron una 2 RC. La media de supervivencia fue 120 (2- 575) días y el 29% sobrevivió al año de seguimiento. El uso de un segundo régimen intensivo o moderado no brindó ventaja sobre el esquema conservador (prueba log-Rank, p = 0,812). Ninguna variable demostró valor pronóstico sobre la supervivencia a 1 año. La duración de la primera RC (OR 6,78, p = 0,005, 95% IC: 1,7532-26,2803) y recibir un primer tratamiento intensivo (OR 0,22, p = 0,018, 95% IC: 0,0661-0,7813) fueron variables pronósticas de falla terapéutica para alcanzar la 2 RC. Conclusiones: Poseer una primera RC < 1 año fue un factor de riesgo importante para no integrar una 2 RC. No se identificaron factores pronósticos de supervivencia ni superioridad de alguno de los esquemas de rescate empleados.

Aims: To identify those factors that affect therapeutic response to achieve a second remission (2 RC) in patients with acute lymphoblastic leukaemia (ALL) in relapse. Methods: Observational, descriptive and analytical study nested in a retrospective cohort of adults (> 18 years-old) ALL carriers treated during the period from 2008 to 2014 that disrupted the HGMLAL07 protocol when relapse was detected and began another therapeutic scheme. Results: The study included 69 patients, of whom 62.3% (n = 43) were males, and the mean age was 29 years-old. The therapeutic regimens used were: high intensity (55.1%) [Hyper-CVAD (n = 34), IDA-Flag (n = 1), mitoxantrone-DARAC (n = 3) ], moderate intensity (4.3%) [Re-induction schemes (n = 3) ], and palliative treatment of low intensity with transfusion support (40.6%, n = 28).Only 19 patients (27.5%) achieved a 2 RC. The median overall survival was 120 (2-575) days, 29% of patients were alive at one year. Using a high or moderate intensity regime as the rescue scheme gave no advantage over the conservative one (log-rank test, P = .812). None of the variables showed prognostic value of survival at one year. The duration of the first RC (OR 6.78, P = .005, 95% CI; 1.75 -26.28) and receiving high intensity treatment (OR 0.22, P = 018, 95% CI: 0.06 -0.78) were predictors of treatment failure to achieve 2 RC. Conclusions: To achieve a first RC < 1 year was an important risk factor for not achieving a 2 RC. No prognostic factors for survival were identified. None of the schemes used for rescue showed superiority.

Introducción: metformina es un medicamento antidiabético evaluado en varios modelos in vitro e in vivo de cáncer ya que es capaz de incrementar la proteincinasa activada por adenosin monofosfato y bloquear las vías de señalización tumoral. Objetivo: evaluar los efectos antitumorales de metformina en línea celular MOLT-4 en pacientes bajo tratamiento de inducción a la remisión. Materiales y métodos: fase in vitro: ensayo en línea celular MOLT-4 adicionando metformina 40 mM evaluando la viabilidad y ciclo celular mediante citometría de flujo. Fase clínica: Estudio de casos y controles en pacientes portadores de leucemia linfoblástica aguda de novo, adicionando metformina 850 mg cada ocho horas en etapa de pretratamiento e inducción a la remisión, contra el registro histórico del protocolo institucional HGMLAL07. Para el análisis estadístico se utilizó el test de chi-cuadrado, estudio multivariado para factores de riesgo y evaluación del efecto sobre la remisión mediante Odds Ratio. Resultados: ensayo celular: meformina inhibió la viabilidad celular a las 120 horas, reduciendo el porcentaje de células en fase S. Estudio clínico: en un total de 151 pacientes, el 29,1% correspondieron al brazo de metformina. La mayor tasa de respuesta favorable a esteroides como de remisiones completas se encontraron en los pacientes que recibieron metformina (59,1% versus 26,2% y 81,8% versus 57,9%) con significancia estadística (p= 0.000* y 0,006 95% IC). Conclusiones: la adición de metformina a la quimioterapia incremento la respuesta favorable a esteroides y las tasas de remisiones completas. In vitro, y semejante a otros modelos, metformina arresta a las células en G0/G1, induciendo una disminución en la viabilidad celular. MÉD.UIS. 2015;28(2):221-8

Introduction: metformin, antidiabetic drug evaluated in several in vitro and in vivo cancer models, is able of increasing the adenosine monophosphate activated protein kinase and block tumor signaling pathways. Objetive: to evaluate the antitumor effects of metformin in MOLT-4 cell line and in patients under treatment for remission induction. Materials and methods: in vitro phase: essay in MOLT-4 cell line adding metformin 40 mM evaluating the viability and cell cycle by flow cytometry. Clinic phase: Case-control study in patients with de novo acute lymphoblastic leukemia, adding metformin three time a day on pretreatment stage and remission induction, against the historical record of the institutional protocol HGMLAL07. Statistical analysis: chi-square analysis, multivariate analysis for risk factors and evaluation of the effect over the remission by Odds ratio. Results: celular assay: metformina inhibited cell viability at 120 hours reducing the percentage of cells in phase S. Clinical assay: 151 patients were studied, 29.1% on metformina arm. The highest rate of good steroid response and complete remissions were found in patients who received metformin (59,1% versus 26,2% and 81,8% vs 57,9%) statistically significant (p= 0.000* and 0.006, 95% IC). Conclusions: the addition of metformin to chemotherapy increased the good steroids response to steroids and rates of complete remissions. In vitro, and similar to other models, metformin arrest cells in G0/G1, inducing a decrease in cell viability. MÉD.UIS. 2015;28(5):221-8

In order to assess the mortality and toxicity of the Hyper-CVAD protocol used as first-line treatment of acute lymphoblastic leukemia, a retrospective cohort study was performed in patients less than 40 years of age from March to September 2011 treated with Hyper-CVAD regimen. Mortality and toxicity was compared with the results of patients treated with the institutional HGMLAL07 regimen between 2009-2012. 18 patients were included; the median age was 26 years old. Complete remissions (67.7% versus 81.9%) as well as one-year (40% versus 62%) and 2 year survival rates (18% versus 34%) were lower with the Hyper-CVAD regimen. By selecting only patients younger than 35 years, the effectiveness of Hyper-CVAD was also lower. In our experience and because of its high cost and toxicity, the Hyper-CVAD regimen should be limited to patients with relapsed or refractory leukemia.

Con el objetivo de evaluar la mortalidad y toxicidad del protocolo Hyper-CVAD utilizado como primera línea de tratamiento de la leucemia linfoblástica aguda se realizó un estudio de cohorte retrospectiva en pacientes de 40 años a menos durante marzo a septiembre de 2011 atendidos con el régimen Hyper-CVAD. La mortalidad y toxicidad se comparó con los resultados de los pacientes atendidos con el régimen institucional HGMLAL07 entre 2009 a 2012. Se incluyeron 18 pacientes, la mediana de edad fue de 26 años. Tanto las remisiones completas (67,7% frente a 81,9%) como la supervivencia a un año (40% frente a 62%) y 2 años (18% frente a 34%) fueron menores con el régimen Hyper-CVAD. Al seleccionar exclusivamente pacientes menores de 35 años, la eficacia de Hyper-CVAD también fue menor. Según esta experiencia y debido a su alto costo y toxicidad, el régimen Hyper-CVAD debe de limitarse a aquellos pacientes con leucemias refractarias o en recaída.

In order to assess the mortality and toxicity of the Hyper-CVAD protocol used as first-line treatment of acute lymphoblastic leukemia, a retrospective cohort study was performed in patients less than 40 years of age from March to September 2011 treated with Hyper-CVAD regimen. Mortality and toxicity was compared with the results of patients treated with the institutional HGMLAL07 regimen between 2009-2012. 18 patients were included; the median age was 26 years old. Complete remissions (67.7% versus 81.9%) as well as one-year (40% versus 62%) and 2 year survival rates (18% versus 34%) were lower with the Hyper-CVAD regimen. By selecting only patients younger than 35 years, the effectiveness of Hyper-CVAD was also lower. In our experience and because of its high cost and toxicity, the Hyper-CVAD regimen should be limited to patients with relapsed or refractory leukemia.

Con el objetivo de evaluar la mortalidad y toxicidad del protocolo Hyper-CVAD utilizado como primera línea de tratamiento de la leucemia linfoblástica aguda se realizó un estudio de cohorte retrospectiva en pacientes de 40 años a menos durante marzo a septiembre de 2011 atendidos con el régimen Hyper-CVAD. La mortalidad y toxicidad se comparó con los resultados de los pacientes atendidos con el régimen institucional HGMLAL07 entre 2009 a 2012. Se incluyeron 18 pacientes, la mediana de edad fue de 26 años. Tanto las remisiones completas (67,7% frente a 81,9%) como la supervivencia a un año (40% frente a 62%) y 2 años (18% frente a 34%) fueron menores con el régimen Hyper-CVAD. Al seleccionar exclusivamente pacientes menores de 35 años, la eficacia de Hyper-CVAD también fue menor. Según esta experiencia y debido a su alto costo y toxicidad, el régimen Hyper-CVAD debe de limitarse a aquellos pacientes con leucemias refractarias o en recaída.