Acute lymphoblastic leukemia (ALL) represents around 25% of adult acute leukemias. Despite the increasing improvement in the survival rate of ALL patients during the last decade, the heterogeneous clinical and molecular features of this malignancy still represent a major challenge for treatment and achieving better outcomes. To identify aberrantly expressed genes in bone marrow (BM) samples from adults with ALL, transcriptomic analysis was performed using Affymetrix Human Transcriptome Array 2.0 (HTA 2.0). Differentially expressed genes (DEGs) (±2-fold change, p-value < 0.05, and FDR < 0.05) were detected using the Transcriptome Analysis Console. Gene Ontology (GO), Database for Annotation, Visualization, and Integrated Discovery (DAVID), and Ingenuity Pathway Analysis (IPA) were employed to identify gene function and define the enriched pathways of DEGs. The protein-protein interactions (PPIs) of DEGs were constructed. A total of 871 genes were differentially expressed, and DNTT, MYB, EBF1, SOX4, and ERG were the top five up-regulated genes. Meanwhile, the top five down-regulated genes were PTGS2, PPBP, ADGRE3, LUCAT1, and VCAN. An association between ERG, CDK6, and SOX4 expression levels and the probability of relapse and death was observed. Regulation of the immune system, immune response, cellular response to stimulus, as well as apoptosis signaling, inflammation mediated by chemokines and cytokines, and T cell activation were among the most altered biological processes and pathways, respectively. Transcriptome analysis of ALL in adults reveals a group of genes consistently associated with hematological malignancies and underscores their relevance in the development of ALL in adults.
Gene Expression Profiling , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Transcriptome , Biomarkers , Recurrence , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Computational Biology , SOXC Transcription Factors
Patients with acute lymphoblastic leukemia (ALL) undergoing induction decrease their physical capacity, lose muscle mass, and decrease their quality of life (QOL). The safety, feasibility, and benefits of exercise during chemotherapy have been proven, but the effects of cross-training activities have yet to be analyzed. To measure the effects of cross-training on body composition, physical performance, and QOL, a blind randomized clinical trial was carried out. A total of 33 patients were included and randomized into a cross-training exercise group (CEG), a resistance exercise group (REG), and a control group (CG). During induction, patients received an exercise routine three to five days a week for 30 to 50 min each. Body composition, QOL, and physical performance were measured at baseline, up to discharge, and at a follow-up of two months. Body composition improved in the REG and CEG. In the CG, muscle mass decreased and fat mass increased (p = 0.020 and 0.020, respectively). The REG and CEG had significant positive improvements in physical performance compared to the CG. QOL showed no differences in any group (p = 0.340). Cross-training and resistance exercise are essential to improve body composition and physical performance during induction. Considering the prognostic value of physical performance, we propose integrated training exercises as adjuvant therapy in adult patients with ALL.
Introducción. El bazo es un órgano linfoide implicado en el reconocimiento antigénico, la depuración de patógenos y la remoción de eritrocitos envejecidos o con inclusiones citoplasmáticas. La esplenectomía es una técnica utilizada tanto para el diagnóstico (linfomas), el tratamiento (trombocitopenia inmune, anemia hemolítica adquirida) y la curación (microesferocitosis hereditaria) de diversas enfermedades. Métodos. Describir los principales cambios hematológicos y complicaciones asociadas al procedimiento de esplenectomía. Discusión. Los cambios posteriores a la esplenectomía pueden ser inmediatos, como la aparición de cuerpos de Howell-Jolly, la trombocitosis y la presencia de leucocitosis durante las primeras dos semanas. Otras complicaciones tempranas incluyen la presencia de trombosis, en especial en pacientes con factores de riesgo secundarios (edad, sedentarismo, manejo hospitalario, obesidad) o un estado hipercoagulable (diabetes, cáncer, trombofilia primaria), siendo tanto el flujo de la vena porta como el volumen esplénico los principales factores de riesgo para su aparición. Las complicaciones tardías incluyen la alteración en la respuesta inmune, aumentando el riesgo de infecciones por bacterias encapsuladas, en conjunto con una reducción en los niveles de IgM secundario a la ausencia de linfocitos B a nivel de bazo. Debido al riesgo de infecciones, principalmente por Streptococcus pneumoniae, la esplenectomía parcial se ha considerado una opción. Conclusión. Una adecuada valoración de la indicación de esplenectomía y la identificación precoz de complicaciones posoperatorias son fundamentales para reducir la mortalidad asociada a la esplenectomía
Introduction. The spleen is a lymphoid organ involved in antigen recognition, pathogen clearance, and removal of aged erythrocytes or those with cytoplasmic inclusions. Splenectomy is a technique used for diagnosis (lymphomas), treatment (immune thrombocytopenia, acquired hemolytic anemia), and cure (hereditary microspherocytosis) of various diseases. Methods. To describe the main hematological changes and complications associated with the splenectomy procedure. Discussion. Changes after splenectomy can be considered immediate: the appearance of Howell-Jolly bodies, thrombocytosis, and leukocytosis during the first two weeks. Other complications include the presence of thrombosis, especially in patients with risk factors (age, sedentary lifestyle, long hospital stay, obesity) or a hypercoagulable state (diabetes, cancer, primary thrombophilia), with both portal vein flow and splenic volume being the main risk factors for its appearance. Late complications include altered immune response, increased risk of infections by encapsulated bacteria, and a reduction in IgM levels secondary to the absence of B lymphocytes in the spleen; due to the risk of diseases mainly by Streptococcus pneumoniae, partial splenectomy has been considered an option. Conclusion. An adequate assessment of the indication for splenectomy and the early identification of complications are essential to reduce the mortality associated with splenectomy
Humans , Splenectomy , Splenic Diseases , Postoperative Complications , Thrombosis , Erythrocyte Inclusions , Leukocytosis
Antecedentes: La obesidad se ha asociado con estado proinflamatorio de bajo grado que se ha relacionado con el desarrollo del cáncer en general incluyendo el hematológico. Objetivos: El presente trabajo tiene el objetivo de identificar la asociación del diagnóstico de obesidad acorde al índice de masa corporal (IMC) con indicadores pronóstico de pacientes adultos con Leucemia Linfoblástica Aguda (LAL). Pacientes y Método: Se trata de un estudio observacional, retrospectivo que incluyó pacientes hospitalizados con diagnóstico de LAL de linaje de células B. Se estimó el IMC con base al peso y talla registrado al ingreso de los pacientes. Se determinó el riesgo de recaídas, recaídas a médula ósea y supervivencia. Se utilizó el método de Kaplan-Meier mediante el test log-Rank en el análisis estadístico. Resultados: Se incluyeron 128 pacientes. El peso y el IMC no mostraron una asociación significativa con el riesgo de recaídas. La frecuencia de recaída a médula ósea fue del 43,8%. La obesidad no impactó con la supervivencia global (p = 0,640) ni en la supervivencia libre de enfermedad (p = 0,527). La presencia de obesidad no se comportó como una variable de riesgo de recaída (p = 0,873). El IMC con punto de corte de 30 kg/m2 no se comportó como un factor de riesgo de recaída (OR 1.078). Conclusión: La obesidad no es un factor de riesgo independiente para el pronóstico de los pacientes adultos portadores de Leucemia Linfoblástica Aguda de linaje B.
Background: Obesity has been associated with a low-grade proinflammatory state, and it has been related to the development of cancer in general, including hematologic cancer. Aim: The present work aimed to identify the association of the diagnosis of obesity according to the body mass index (BMI) with prognostic factors of adult patients with Acute Lymphoblastic Leukemia (ALL). Patients and Method: This observational, retrospective study included hospitalized patients diagnosed with ALL of the B-cell lineages. BMI was estimated based on the weight and height registered on clinical records at the admission of the patients. The relapse risk and bone marrow relapse were determined, and the survival rate was measured. The statistical analysis included the Kaplan-Meier method using the log-Rank test. Results: This study included 128 clinical records of patients. Weight had no significant association with relapse risk. The frequency of bone marrow relapse was 43.8%. Obesity did not impact overall survival (p = 0.640) or disease-free survival (p = 0.527). The presence of obesity does not behave as a relapse risk variable (p = 0.873). BMI with a 30 kg/m2 cut-off point did not influence relapse risk (OR 1.078). Conclusion: Obesity is not an independent risk factor for the prognosis of adult patients with Acute Lymphoblastic Leukemia B-lineage.
Background: Leukemia is a neoplasm with high incidence and mortality rates. Mitotic death has been observed in tumor cells treated with chemotherapeutic agents. Ras family proteins participate in the transduction of signals involved in different processes, such as proliferation, differentiation, survival, and paradoxically, initiation of cell death. Methods: This study investigated the effect of H-Ras expression on human T-cell acute lymphoblastic leukemia MOLT-4 cells. Cells were electroporated with either wild-type (Raswt) or oncogenic mutant in codon 12 exon 1 (Rasmut) versions of H-Ras gene and stained for morphological analysis. Cell viability was assessed using trypan blue staining and cell cycle analysis using flow cytometry. H-Ras gene expression was determined using quantitative real-time reverse transcription polymerase chain reaction. The t, ANOVA, and Scheffe tests were used for statistical analysis. Results: Human T-cell acute lymphoblastic leukemia MOLT-4 cells showed nuclear fragmentation and presence of multiple nuclei and micronuclei after transfection with either wt or mutant H-Ras genes. Cell cycle analysis revealed a statistically significant increase in cells in the S phase when transfected with either wt (83.67%, P<0.0005) or mutated (81.79%, P<0.0001) H-Ras genes. Although similar effects for both versions of H-Ras were found, cells transfected with the mutated version died at 120 h of mitotic catastrophe. Conclusion: Transfection of human T-cell acute lymphoblastic leukemia MOLT-4 cells with either normal or mutated H-Ras genes induced alterations in morphology, arrest in the S phase, and death by mitotic catastrophe.
BACKGROUND: Obesity has been associated with a low-grade proinflammatory state, and it has been related to the development of cancer in general, including hematologic cancer. AIM: The present work aimed to identify the association of the diagnosis of obesity according to the body mass index (BMI) with prognostic factors of adult patients with Acute Lymphoblastic Leukemia (ALL). PATIENTS AND METHOD: This observational, retrospective study included hospitalized patients diagnosed with ALL of the B-cell lineages. BMI was estimated based on the weight and height registered on clinical records at the admission of the patients. The relapse risk and bone marrow relapse were determined, and the survival rate was measured. The statistical analysis included the Kaplan-Meier method using the log-Rank test. RESULTS: This study included 128 clinical records of patients. Weight had no significant association with relapse risk. The frequency of bone marrow relapse was 43.8%. Obesity did not impact overall survival (p = 0.640) or disease-free survival (p = 0.527). The presence of obesity does not behave as a relapse risk variable (p = 0.873). BMI with a 30 kg/m2 cut-off point did not influence relapse risk (OR 1.078). CONCLUSION: Obesity is not an independent risk factor for the prognosis of adult patients with Acute Lymphoblastic Leukemia B-lineage.
Body Mass Index , Obesity , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Male , Retrospective Studies , Female , Obesity/complications , Adult , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Risk Factors , Middle Aged , Young Adult , Prognosis , Adolescent , Recurrence , Aged , Kaplan-Meier Estimate , Disease-Free Survival
IL-15 is a proinflammatory myokine essential for activating NK cells and CD8+ T lymphocytes, and its overexpression has been related to reducing overall survivorship in patients with acute lymphoblastic leukemia (ALL). Physical exercise has been shown to be safe, feasible, and beneficial in hematological cancers. Exercise requires the activation of muscles that secrete cytokines, such as IL-15, causing immune mobilization. The objective was to compare the outcomes of two training routines on IL-15 and survival prognosis in adult patients diagnosed with ALL. A blind randomized clinical study was carried out where twenty-three peripheral blood samples were obtained pre and postexercise intervention from patients categorized into three types of intervention: the resistance exercise group (REG), the cross-training exercise group (CEG), and the control group (CG). Changes in IL-15 levels during the intervention were not significant in any of the groups (CG p = 0.237, REG p = 0.866, and CEG p = 0.678). However, 87.5% of patients who received an exercise intervention achieved remission, while only 21.73% experienced a relapse. There were no deaths during the study. Although IL-15 level adaptation in the REG and the CG performed similarly, the REG induced a better clinical outcome. Resistance exercises may help improve survival prognosis and reduce relapses in patients with ALL.
Objective: In the last two years progress was made in molecular, physio pathological understanding and the form of transmission of COVID-19, and different therapeutic strategies have been explored to deal with the situation of the pandemic. However, the evaluation of certain genes that participate in the metabolism and transport of these drugs has not been fully explored. A lack of response to treatment and a lower survival have been observed that may be due to the presence of the ABCB1 drug resistance gene. Our research group analyzed whether the expression levels of the ABCB1 gene are associated with comorbidities, treatments, overall survival and risk of death in patients with severe COVID-19. Methods: The expression levels of the ABCB1 gene were analyzed by RT-qPCR in 61 patients diagnosed with COVID-19. The association between the levels of expression, the risk variables and different treatments were determined by the Chi-Square test and the Fisher's exact test. Global Survival (GS) was determined by the Kaplan-Meier method. The impact of high levels of expression and the risk of death was performed by odds ratio. Results: The different risk variables showed that patients with either high or absent levels of ABCB1 gene expression presented a greater risk of death (OR 3.08, 95%, CI 1.02-9.26) as well as need for ventilatory support (OR 2.8, 95%, CI 0.98 -8.5). Patients with diabetes and COVID-19, treated with metformin, were associated with a lower risk of death (OR 1.11, 95%, CI 0.38-3.22). OS with respect to high or absent levels of expression of the ABCB1 gene was lower. Conclusion: High levels or null expression of the ABCB1 gene are associated with a higher risk of death or progression of the disease, the use of metformin in patients with COVID-19 confers a lower risk of death.
BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by different genetic alterations that cause changes in the normal mechanisms of differentiation, which are associated with chemoresistance. The ABCB1 gene is part of a family of ATP-binding cassette (ABC) transporter genes involved in the progression of various types of cancer. The following work aimed to evaluate the expression levels of the ABCB1 gene and the C3435T SNP with the response to first-line treatment and survival in patients with AML. METHODS: In total 135 samples were taken to isolate total RNA and DNA at the beginning of the treatment. Expression analysis by RT-qPCR and SNP C3435T assessment method were performed for real-time Polymerase chain reaction (qPCR). RESULTS: The expression levels impact on the survival of patients with AML compared to low or absent levels; the CC genotype was found in 22.9%, the CT genotype was found in 47.4%, and the TT genotype was found in 29.6%, the presence of the C3435T SNP, the TT genotype also impacts with a lower survival compared to CT and CC genotypes. In addition, it was shown that the dominant model significantly impacts survival. CONCLUSION: In conclusion, we have found that the overexpression of the ABCB1 gene, as well as the presence of the TT genotype of the C3435T SNP, contributes to a worse prognosis in AML.
Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathology , Polymorphism, Single Nucleotide , ATP Binding Cassette Transporter, Subfamily B/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Mexico , Middle Aged , Real-Time Polymerase Chain Reaction , Survival Rate , Young Adult
Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by the clonal expansion of hematopoietic lymphoid progenitors. With new target therapies, the survival of adults with ALL has improved in the past few decades. Unfortunately, there are no large ALL patient series in many Latin American countries. Data from the Acute Leukemia Workgroup that includes five Mexico City referral centers were used. Survival was estimated for adult patients with ALL during 2009-2015. In total, 559 adults with ALL were included. The median age was 28 years; 67% were classified into the adolescent and young adult group. Cytogenetic information was available in 54.5% of cases. Of the 305 analyzed cases, most had a normal caryotype (70.5%) and Philadelphia-positive was present in 16.7%. The most commonly used treatment regimen was hyper-CVAD. In approximately 20% of cases, there was considerable delay in the administration of chemotherapy. Primarily refractory cases accounted for 13.1% of patients. At the time of analysis, 26.7% of cases had survived. The 3-year overall survival was 22.1%. The main cause of death was disease progression in 228 (55.6%). Clinical and public health strategies are needed to improve diagnosis, treatment and survivorship care for adult with ALL. This multicentric report represents the largest series in Mexico of adult ALL patients in which a survival analysis and risk identification were obtained.
Leukemia, Myeloid, Acute/epidemiology , Adult , Female , Humans , Leukemia, Myeloid, Acute/mortality , Male , Mexico , Survival Analysis
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.
Leukemia/epidemiology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Male , Mexico/epidemiology , Middle Aged , Retrospective Studies , Sex Distribution , Tertiary Care Centers , Urban Health , Young Adult
BACKGROUND: The incidence of acute leukemia (AL) has increased. Its prognosis is variable and depends on several baseline characteristics with a highly heterogeneous presentation. In Mexico, large-scale descriptive studies have not yet been published; the objective of this study was to analyze the initial basic characteristics of patients diagnosed with AL in our population. PATIENTS AND METHODS: In this multicenter, retrospective study, 1018 patients ≥ 16 years of age and diagnosed with AL between 2009 and 2014, were included. We described age, gender, complete blood count, and AL subtype according to flow cytometry analysis. RESULTS: Acute lymphoblastic leukemia (ALL) was as common as acute myeloid leukemia (AML) (51% vs. 49%). The median age was 31 years. Only 9.6% of patients with ALL were positive for the Philadelphia chromosome. No gender differences were observed. The median age at presentation of AML was 43 years. Acute promyelocytic leukemia was the most frequent AML subtype (38.3%), with a median age of 37 years. CONCLUSION: ALL is equally as frequent as AML in patients ≥16 years of age. Philadelphia-positive prevalence is less frequent than that reported in literature. AML cases occur in a younger age in comparison with other countries. There is a higher rate of acute promyelocytic leukemia among our patients compared with other non-Latin American populations. This study is the largest ever performed in Mexico regarding descriptive AL data.
Leukemia, Myeloid, Acute/epidemiology , Acute Disease/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Incidence , Leukemia, Myeloid, Acute/genetics , Male , Mexico , Middle Aged , Philadelphia Chromosome , Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Prognosis , Retrospective Studies , Young Adult
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.
Humans , Male , Adult , Prognosis , Antineoplastic Combined Chemotherapy Protocols , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Treatment Failure , Survivorship
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.
Leukemia/epidemiology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Child , Child, Preschool , Cities , Female , Humans , Infant , Male , Mexico/epidemiology , Middle Aged , Referral and Consultation , Retrospective Studies , Sex Distribution , Urban Health , Young Adult
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.
Precursor Cell Lymphoblastic Leukemia-Lymphoma , Prognosis
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.
Metformin , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Steroids
