Mieloma múltiple: consideraciones especiales sobre el diagnóstico / Multiple Myeloma: Special Diagnostic Considerations

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.

Usefulness of the neutrophil-to-lymphocyte, monocyte-to-lymphocyte and lymphocyte-to-platelet ratios for the prognosis of COVID-19-associated complications.

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 x 103/µL, with a neutrophil mean of 8.0 x 103/µL. 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.

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/µL y la de neutrófilos, de 8.0 × 103/µL. 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.

Utilidad de los índices neutrófilo/linfocito, monocito/linfocito y linfocito/plaqueta para el pronóstico de complicaciones asociadas a COVID-19 / Usefulness of the neutrophil-to-lymphocyte, monocyte-to-lymphocyte and lymphocyte-to-platelet ratios for the prognosis of COVID-19-associated complications

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.

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.

Efecto de la administración de vitamina K en las complicaciones asociadas con enfermedad hepática crónica terminal / Effect of the administration of vitamin K on the complications associated with end stage liver disease

Resumen ANTECEDENTES La administración de vitamina K se restringe a situaciones, como antídoto de los antagonistas de vitamina K y enfermedad hemorrágica del recién nacido, pero debido a su papel en la hemostasia, su administración se ha extendido al tratamiento de otras enfermedades, como la enfermedad hepática crónica. OBJETIVO Identificar la eficacia de adicionar vitamina K al tratamiento de los pacientes con insuficiencia hepática terminal con algún estado de descompensación. MATERIAL Y MÉTODO Estudio de casos y controles retrospectivo realizado en el periodo 2016-2017 en pacientes con enfermedad hepática crónica estadio Child-Pugh C durante un episodio de descompensación. La vitamina K (bisulfito sódico de menadiona) se administró a dosis de 10 mg vía intramuscular cada 12 h durante tres días. RESULTADOS Se estudiaron 60 pacientes, 30 recibieron vitamina K, en caso de un evento hemorrágico se administró en conjunto terapia de sustitución con plasma fresco congelado y crioprecipitados. La media de edad fue de 60 (25-86) años, todos los casos eran del género masculino. La principal causa de complicación fue la hemorragia (85%). Cinco casos (8.3%) fallecieron por reactivación de la hemorragia. Administrar vitamina K no acortó las pruebas de coagulación (TP, TTPa, INR) ni mostró beneficio en la mortalidad. Sólo la trombosis como la encefalopatía mostró asociación con la mortalidad. CONCLUSIÓN La adición de vitamina K no influye en las complicaciones en pacientes con enfermedad hepática terminal.

Abstract BACKGROUND The administration of vitamin K are restricted to situations such as an antidote for vitamin K antagonists and hemorrhagic disease of the newborn, but due to its role in hemostasis, its use has been extended to other diseases, such as terminal chronic liver disease. OBJECTIVE To identify the efficacy of adding vitamin K to the management of patients with terminal hepatic insufficiency with some state of decompensation. MATERIAL AND METHOD A retrospective case-control study was done between 2016-2017 in patients with Child-Pugh C chronic liver disease during an episode of decompensation. Vitamin K (menadione sodium bisulfite) was administered at a dose of 10 mg intramuscular every 12 h for three days. RESULTS A total of 60 patients were studied, 30 received vitamin K, in the case of a hemorrhagic event, replacement therapy with fresh frozen plasma and cryoprecipitates were administered together. The mean age was 60 (25-86) years; all were male. Hemorrhage (85%) was the main cause of complication. Five cases (8.3%) died due to reactivation of the hemorrhage. The administration of vitamin K did not shorten the coagulation tests (TP, aPTT, INR) nor showed a mortality benefit. Only thrombosis such as encephalopathy showed an association on mortality. CONCLUSION The addition of vitamin K does not influence the complications in patients with terminal liver disease.

[The age and sex frequencies of patients with leukemia seen in two reference centers in the metropolitan area of Mexico City]. / Frecuencias de edad y género de pacientes con leucemia en dos centros de referencia del Valle de México.

INTRODUCTION: In developing countries, there is commonly a lack of population-based cancer registries or underreporting, thus not recognizing the true dimensions of the problem. AIM: To describe the age and sex frequencies of the major subtypes of leukemias in two hospitals of reference in the metropolitan area of Mexico City. MATERIAL AND METHODS: This is a descriptive and retrospective study, based on medical records of two hematology services during January 2007 to October 2014; all cases diagnosed with leukemia were included. RESULTS: A total of 1,432 cases were included with a median age of 38 years (range, two months to 115 years). There were significant age differences between subtypes of leukemia (ANOVA test, p = 0.000): chronic lymphocytic with a mean age of 64.8 years, higher than chronic myeloid (43.4 years) and all acute leukemias (lymphoblastic: 32.6 years, myeloblastic 43.5 years). Of the patients, 51.8% (n = 742) were women, although males predominated in chronic myeloid (57.8%) and lymphocytic (60%) leukemia. Acute lymphoblastic leukemia was the more common variety, FABL2 subtype, followed by myeloid leukemia M4, M2, and chronic myeloid. CONCLUSIONS: It is necessary to develop inter-institutional works in order to group data of different population sectors and improve the epidemiological profile of leukemia in Mexico.

Factores pronósticos de remisión en pacientes con leucemia linfoblástica aguda posterior a primer recaída / Prognostic factors of remission in patients with acute lymphoblastic leukemia after a first relapse

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.

[The age and sex frequencies of patients with leukemia seen in two reference centers in the metropolitan area of Mexico City]. / Frecuencias de edad y género de pacientes con leucemia observada en dos centros de referencia del Valle de México.

INTRODUCTION: A lack of a population-based cancer registry or underreporting is common in developing countries, without knowledge of the true dimensions of the problem. AIM: To describe the age and sex frequencies of the major subtypes of leukemias in two reference hospitals in the metropolitan area of Mexico City. MATERIAL AND METHODS: A descriptive and retrospective study, based on medical records of two hematology services during January 2007 to October 2014; all cases diagnosed with leukemia were included. RESULTS: A total of 1,432 cases were included, with a median age of 38 years old (2 months to 115 years). There were significant age differences between subtypes of leukemia (ANOVA test, p = 0.000); chronic lymphocytic with a mean age of 64.8 years, higher than chronic myeloid (43.4 years) and all acute leukemias (lymphoblastic: 32.6 years, myeloblastic 43.5 years). Of the patients, 51.8% (n = 742) were women, although males predominated in chronic myeloid (57.8%) and lymphocytic (60%) leukemia. Acute lymphoblastic leukemia was the more common variety, L2 subtype of the French-American-British classification, followed by myeloid leukemia M4, M2, and chronic myeloid. CONCLUSIONS: it is necessary to develop inter-institutional works in order to group data of different population sectors and improve the epidemiological profile of leukemias in Mexico.

Edad y recuento leucocitario como factores pronósticos en leucemia linfoblástica aguda: cohorte HGMLAL07 / Age and leukocyte count as prognostic factors on acute lymphoblastic leukemia: HGMLAL07 cohort

Con el objetivo de establecer la cifra de corte de leucocitos y edad con implicación pronostica en adultos con leucemia linfoblástica aguda (LLA), se efectuó un estudio observacional, descriptivo y analítico anidado en la cohorte retrospectiva de pacientes con LLA tratados mediante el protocolo institucional HGMLAL07 durante 2007-2014. Se estudiaron 255 pacientes, el 52.9% (n=135) correspondieron al género femenino y 47.1% (n=120) al género masculino. La media de edad fue de 31 (16-80) años. La supervivencia libre de la enfermedad (SLE) disminuyó en ambos géneros a partir de los 20 años (p=0.001). La media de leucocitos fue 56.1 x 109/L (0.1-850 x 109/L). La SLE disminuyó significativamente a partir de una cifra igual o mayor de 20 x 109/L (p<0.05). Con esto se puede concluir que emplear puntos de corte para leucocitos y edad obtenidos en poblaciones distintas pudiera condicionar una mala clasificación pronostica y un consiguiente tratamiento subóptimo.

In order to establish the cutoff with prognostic implications for white blood cell count and age at diagnosis in adults with acute lymphoblastic leukemia (ALL), we conducted an observational, descriptive and analytical study nested in a retrospective cohort of patients with ALL treated by institutional protocol HGMLAL07 during 2007-2014. We study 255 patients, the 52.9% (n=135) were female and 47.1% (n=120) were male. The mean age was 31 (16-80) years-old. The disease-free survival (DFS) decreases in both genders after 20 years-old (p = 0.001). Leukocyte count average was 56.1 x 109/L (0.1-850 x 109/L). DFS decreases significantly from an equal or greater leukocyte count of 20 x 109/L (p<0.05). With this results, we can conclude that use foreign cutoff for age and leukocyte count could determine a bad prognosis stratification and a consequent suboptimal treatment.

Efecto de la adición de metformina a un pretratamiento con esteroides en pacientes adultos con leucemia linfoblástica aguda y en la viabilidad de la línea celular MOLT-4 / Effect of metformin to a pretreatment with steroids in adult patients with acute lymphoblastic leukemia and in the viability of the MOLT-4 cell line

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.

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.

[Surgical-pathologic correlation to assess the margin status in wide local excision for early-stages breast cancer]. / Correlación quirúrgico-patológica para evaluar el estado de los bordes en las escisiones locales amplias de cáncer mamario en etapas clínicas tempranas.

OBJETIVE: To know the surgical-pathologic correlation to assess the state of the edges in wide local excisions of breast cancer in clinical stages. MATERIAL AND METHODS: retrospective and descriptive study, conducted in Breast Tumors Unit from Oncology Service of the General Hospital of Mexico, in the period from January 2009 to December 2011, with follow-up in December2012. Were included patients with breast cancer in early clinical stages, subject wide local excisions histopalogic report of a second surgery. RESULTS: From wide local excisions, 119 (28.5%) were due to breast cancer and included. Positive margins after initial surgery were diagnosed in 63 patients (52.9%). The residual tumor found in the second surgery was 39.7%. The variables associated with the presence of positive margins and statistically significant (p≤ 0.05) were: multicentricity, tumor size clinical and pathological, histological subtypes, and tumor grade. The age and clinical stage were not statistically significant. The variables associated with the presence of residual tumor and are statistical relevance (p≤ 0.05) were clinical stage, tumor size, clinical and pathological, histological variant and histological grade. Age and multicentricity were not associated with the presence of residual tumor. CONCLUSION: Although each case must be individualized, these results demonstrate the analyzed factors must be taken into account during the planning of breast conservative procedures, and despite an histopalogical report of margin after an initial surgery, even seconds procedures can be performed to conserve the organ.

[Comparison of the Hyper-CVAD with an institutional regimen for the treatment of acute lymphoblastic leukemia in adults in a hospital of Mexico]. / Comparación del Hyper-CVAD con un régimen institucional en el tratamiento de la leucemia linfoblástica aguda del adulto en un hospital de México.

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.

Comparación del hyper-CVAD con un régimen institucional en el tratamiento de la leucemia linfoblástica aguda del adulto en un hospital de México / Comparison of the hyper-CVAD with an institutional regimen for the treatment of acute lymphoblastic leukemia in adults in a hospital of Mexico

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...

[Effect of metformin addition to an acute lymphoblastic leukemia chemotherapy treatment]. / Metformina adicionada a la quimioterapia contra la leucemia linfoblástica aguda.

BACKGROUND: Recently it has been reported a benefit effect with the use of metformin in patients with malignant disease. Our objective was to evaluate the effect of adding metformin to chemotherapy regimen over the percentage of early relapse in acute lymphoblastic leukemia. METHODS: A prospective, longitudinal and experimental study was performed in patients with de novo acute lymphoblastic leukemia enrolled in the Hospital General de México. They were divided in two groups: first group received chemotherapy + metformin (850 mg three times a day); second group only received standard chemotherapy. The sample was randomized 3:1 in favor of the second group. RESULTS: 93 patients were included (73 treated with chemotherapy + metformin and 20 received standard chemotherapy), with 303 ± 53 days of follow-up. Complete remission was higher in the group without metformin (81.3 % [n = 61] versus 70 % [n = 14]), which also presented more patients with relapse (47.9 % versus 25 %). Overall survival at one year was of 68 % and free survival disease was 64 %, without significant differences between groups. Absence of metformin was the only variable of adverse prognostic considered significant (p = 0.55). Cox regression showed that adding metfomin reduced 56 % the risk of relapse. CONCLUSIONS: The adding metformin to the treatment of leukemias showed that was useful in our research. However, randomized and double-blind studies must be designed in order to express final recommendations about its use.

INTRODUCCIÓN: se ha informado efecto benéfico con metformina en pacientes con cáncer. El objetivo de esta investigación fue evaluar el efecto de adicionar metformina a la quimioterapia sobre las recaídas tempranas en pacientes con leucemia linfoblástica aguda. MÉTODOS: estudio prospectivo, longitudinal y experimental de pacientes portadores de leucemia linfoblástica aguda de novo, realizado en el Hospital General de Mexico. La muestra fue dividida en dos brazos de tratamiento: uno recibió metformina (850 mg cada ocho horas) + quimioterapia; otro recibió únicamente quimioterapia estándar. La distribución de los pacientes fue aleatoria, 3:1 a favor del segundo brazo. RESULTADOS: se incluyeron 93 pacientes (73 recibieron quimioterapia + metformina y 20, quimioterapia estándar); el seguimiento fue de 303 ± 53 días. La remisión completa fue mayor en el grupo sin metformina comparado con el que recibió quimioterapia + metformina (81.3 % [n = 61] y 70 % [n = 14], respectivamente), al igual que las recaídas (47.9 y 25 %, respectivamente). La supervivencia global a un año fue de 68 % y la supervivencia libre de la enfermedad fue de 64 %, sin diferencias entre los grupos. La única variable de pronóstico adverso con relevancia significativa fue la ausencia de metformina (p = 0.55). La regresión de Cox demostró que adicionarla redujo 56 % el riesgo de recaída. CONCLUSIONES: la adición de metformina al tratamiento de la leucemia fue de utilidad en nuestra investigación, sin embargo, deberán diseñarse estudios aleatorizados y doble ciego para emitir recomendaciones definitivas.

[Clinical features of acute leukemia and its relationship to the season of the year]. / Leucemias agudas. Características clínicas y patrón estacional.

BACKGROUND: In 2009, 17.9 % of hospital morbidity by malignant tumors in México corresponded to hematological malignancies, mainly acute leukemia. Some studies suggest a seasonal pattern, since most of the cases are registered during summer. Our objective was to estimate the relationship between the different subtypes of acute leukemia with the age when the disease arose, and the season of the year. METHODS: Retrospective and observational study, based on records of a hematology department from January 2006 to April 2012. Only the patients diagnosed with de novo acute leukemia, stratified according to the French-American-British classification, were included. Seasonal analysis was performed using Edward's periodic model. RESULTS: The study included 833 acute leukemia cases: 48 % of women (400), and 52 % of men (433). Median age was 36.2 ± 19.8 years. Acute lymphoblastic leukemia predominated over acute myeloblastic leukemia subtype M4 (p < 0.05), and we found differences (p < 0.01) between lymphoblastic and myeloblastic leukemias: 32.3 and 41.8. Despite the existence of pronounced peaks in the time series, they did not repeat periodically. CONCLUSIONS: The most common variety of acute leukemia was lymphoblastic type L2, followed by myeloblastic type M4. People over 40 years of age were the most affected. A seasonal pattern of acute leukemias was not observed.

INTRODUCCIÓN: en 2009, 17.9 % de la morbilidad hospitalaria por tumores malignos en México correspondió a neoplasias hematooncológicas, principalmente a leucemias agudas. Algunos estudios sugieren un patrón estacional al presentarse más casos durante el verano. El objetivo de esta investigación fue estimar la relación entre los diferentes subtipos de leucemia aguda, la edad de presentación y la estación del año. MÉTODOS: estudio retrospectivo, observacional, que se llevó a cabo con los registros de enero de 2006 a abril de 2012 en un servicio de hematología; se incluyeron únicamente los pacientes con diagnósticos de novo de leucemia aguda, estratificada según la clasificación de la Asociación Franco-Américo-Británica. El análisis de temporalidad se realizó con el modelo periódico de Edward. RESULTADOS: de los 833 casos de leucemia aguda, 48 % correspondió al sexo femenino y 52 % al masculino; la edad media fue de 36.2 ± 19.8 años. Predominó la leucemia aguda linfoblástica sobre la mieloblástica subtipo M4 (p < 0.05) y se encontraron diferencias (p < 0.01) entre la linfoblástica y la mieloblástica: 32.3 y 41.8. A pesar de existir picos pronunciados en la serie temporal, no se repitieron periódicamente. CONCLUSIONES: la variedad más frecuente fue la L2, seguida por la M4. El grupo de edad más afectado fue el de los mayores de 40 años. No existió patrón estacional de presentación de las leucemias agudas.