RESUMEN
BACKGROUND: Platelet transfusion plays a critical role in the supportive treatment of acute leukaemia patients who receive chemotherapy and haematopoietic stem cell transplantation (HSCT). There are few studies assessing appropriateness of platelet transfusion in this population. An audit was conducted to determine how appropriately platelets are transfused in acute leukaemia patients at a tertiary care health institution. MATERIALS AND METHODS: A six-year retrospective audit was conducted in acute lymphoblastic (ALL) and acute myeloid leukaemia (AML) patients in an Academic Centre. Episodes were assessed as either appropriate or inappropriate based on guidelines from the British Society for Haematology (BSH). Pre-transfusion platelet count, transfusion indication, World Health Organization (WHO) bleeding score, and antibiotic use were all documented. RESULTS: Overall, 745 platelet transfusion episodes in 154 patients were audited. The proportion of episodes appropriately indicated according to BSH guidelines was 75.3%. Paediatrics and Internal Medicine had the lowest and highest proportion of appropriateness by department at 63.9% and 86.8%, respectively. The best alignment to guidelines was found on the wards (82.3%). Inpatient cases were significantly better indicated (p=0.002), whereas therapeutic and HSCT-related transfusions were not. The majority of inappropriate transfusions had a pre-transfusion count >20×109/L without a valid justification (45.1%), whereas appropriate episodes were mainly accounted for by a pre-transfusion count <10×109/L (69%). DISCUSSION: The 25% rate of inappropriate platelet transfusion in acute leukaemia patients underscores the learning needs of physicians, particularly those in training, regarding adequate use of platelets in haematologic malignancies to optimise its utilisation and patient outcome.
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Leucemia Mieloide Aguda/terapia , Transfusión de Plaquetas , Adolescente , Adulto , Niño , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Leucemia Mieloide Aguda/sangre , Masculino , Recuento de Plaquetas , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: The hematology analyzer, Sysmex XN-1000, generates white blood cell count with varying scattering intensities during a complete blood count (CBC) analysis. OBJECTIVES: The objectives of the study were to study the predictive role of median and coefficient of variation of neutrophil scattering items in blood samples for differentiation of leukemic subjects. METHODS: We evaluated six neutrophil scattering parameters: neutrophil side scatter mean intensity, neutrophil side fluorescence light (SFL) mean intensity, neutrophil forward scatter mean intensity, neutrophil side scatter area distribution width (NE-WX), neutrophil SFL area distribution width (NE-WY), and neutrophil forward scatter area distribution width (NE-WZ), measured in white blood cell differential scattergram generated by the hematology analyzer (Sysmex XN-1000) at an academic medical center. RESULTS: We collected 433 blood samples from acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) cases and normal controls. AML group showed highly significant differences in the mean values compared with the control group. Out of six neutrophil scattering items, NE-WX, NE-WY, and NE-WZ showed high efficiency, with area under the curve (AUC) values of 0.764, 0.748, and 0.757, respectively, to differentiate AML from ALL cases and control groups. When comparing combined acute leukemia cases (AML plus ALL) with the control group, NE-WX, NE-WY, and NE-WZ generated highly significant AUC values (0.840, 0.884, and 0.801, respectively). CONCLUSION: The neutrophil scattering parameters generated during CBC analysis provide a new tool for the prediction of acute leukemia and its lineage.
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Recuento de Células Sanguíneas/métodos , Leucemia Mieloide Aguda/sangre , Neutrófilos/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Adolescente , Adulto , Recuento de Células Sanguíneas/instrumentación , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
ABSTRACT Background: The hematology analyzer, Sysmex XN-1000, generates white blood cell count with varying scattering intensities during a complete blood count (CBC) analysis. Objectives: The objectives of the study were to study the predictive role of median and coefficient of variation of neutrophil scattering items in blood samples for differentiation of leukemic subjects. Methods: We evaluated six neutrophil scattering parameters: neutrophil side scatter mean intensity, neutrophil side fluorescence light (SFL) mean intensity, neutrophil forward scatter mean intensity, neutrophil side scatter area distribution width (NE-WX), neutrophil SFL area distribution width (NE-WY), and neutrophil forward scatter area distribution width (NE-WZ), measured in white blood cell differential scattergram generated by the hematology analyzer (Sysmex XN-1000) at an academic medical center. Results: We collected 433 blood samples from acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) cases and normal controls. AML group showed highly significant differences in the mean values compared with the control group. Out of six neutrophil scattering items, NE-WX, NE-WY, and NE-WZ showed high efficiency, with area under the curve (AUC) values of 0.764, 0.748, and 0.757, respectively, to differentiate AML from ALL cases and control groups. When comparing combined acute leukemia cases (AML plus ALL) with the control group, NE-WX, NE-WY, and NE-WZ generated highly significant AUC values (0.840, 0.884, and 0.801, respectively). Conclusion: The neutrophil scattering parameters generated during CBC analysis provide a new tool for the prediction of acute leukemia and its lineage.
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Humanos , Masculino , Femenino , Niño , Adolescente , Adulto , Persona de Mediana Edad , Adulto Joven , Recuento de Células Sanguíneas/métodos , Leucemia Mieloide Aguda/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Neutrófilos/metabolismo , Recuento de Células Sanguíneas/instrumentación , Estudios de Casos y ControlesRESUMEN
We investigated the differences between the serum proteomic spectral characteristics of acute myeloid leukemia (AML) patients and those of healthy people. We collected peripheral blood serum samples from 62 AML patients and 15 healthy controls. After removing high-abundance proteins, low-abundance serum proteins were separated using two-dimensional gel electrophoresis to identify differences between AML patients and healthy people. We investigated the different protein dots by mass fingerprint analysis, and evaluated the results using the Masort retrieval program provided by the MSDB protein bank. To further investigate the relationship between standard chemotherapy treatment efficacy and differences in protein patterns, we divided 21 patients into two groups (A and B) according to the efficacy of standard chemotherapy. Compared with the healthy cases, the AML patients demonstrated significant abnormal expression in 14 proteins (P < 0.05); α1-trypsin inhibitor (P < 0.01), prealbumin (P < 0.01), apolipoprotein E (P < 0.010), and apolipoprotein A-IV (P < 0.01) expression decreased, whereas haptoglobin HP2 (P < 0.05), serum exogenous lectin (P < 0.05), H factor homologue protein (P < 0.05), and serum amyloid A1 (P < 0.01) expression increased. Further stratified analysis revealed that patients with high serum lectin expression had poor outcomes. The study revealed various proteins with differential expression levels in the peripheral blood of AML patients, and the difference in serum lectin expression is related to the efficiency of standard chemotherapy. Therefore, these proteins are potential diagnosis markers or prognostic indicators of AML.
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Biomarcadores de Tumor/sangre , Leucemia Mieloide Aguda/sangre , Proteoma/química , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteoma/genética , Proteoma/metabolismoRESUMEN
Acute myeloid leukemia (AML) consists in a cancer of early hematopoietic cells arising in the bone marrow, most often of those cells that would turn into white blood cells (except lymphocytes). Chemotherapy is the treatment of choice for AML but one of the major complications is that current drugs are highly toxic and poorly tolerated. In general, treatment for AML consists of induction chemotherapy and post-remission therapy. If no further post-remission is given, almost all patients will eventually relapse. Histamine, acting at histamine type-2 (H2) receptors on phagocytes and AML blast cells, helps prevent the production and release of oxygen-free radicals, thereby protecting NK and cytotoxic T cells. This protection allows immune-stimulating agents, such as interleukin-2 (IL-2), to activate cytotoxic cells more effectively, enhancing the killing of tumor cells. Based on this mechanism, post-remission therapy with histamine and IL-2 was found to significantly prevent relapse of AML. Alternatively, another potentially less toxic approach to treat AML employs drugs to induce differentiation of malignant cells. It is based on the assumption that many neoplastic cell types exhibit reversible defects in differentiation, which upon appropriate treatment results in tumor reprogramming and the induction of terminal differentiation. There are promissory results showing that an elevated and sustained signaling through H2 receptors is able to differentiate leukemia-derived cell lines, opening the door for the use of H2 agonists for specific differentiation therapies. In both situations, histamine acting through H2 receptors constitutes an eligible treatment to induce leukemic cell differentiation, improving combined therapies.
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Células Sanguíneas/metabolismo , Leucemia Mieloide Aguda/metabolismo , Receptores Histamínicos H2/sangre , Receptores Histamínicos H2/metabolismo , Histamina/metabolismo , Humanos , Interleucina-2/metabolismo , Leucemia Mieloide Aguda/sangre , MasculinoRESUMEN
Hyperleukocytic acute myeloid leukemia (AML) is associated with pulmonary complications and high early mortality rate, but given its rarity, data on chest radiographic presentation are scarce.We retrospectively reviewed the charts of 73 AML patients admitted with white blood cell count >100â×â10/L between 2003 and 2014 in order to describe the chest radiographic and computed tomography (CT) findings and to correlate them with AML subtype and respiratory symptoms.Forty-two of the 73 patients (58%) overall and 36 of the 54 patients (67%) with clinical signs of pulmonary leukostasis had abnormal radiographs on admission. The presence of radiographic abnormalities was significantly associated with dyspnea and oxygen/ventilatory support requirements (Pâ<â0.01) and with day 28 mortality (45% vs 13%, Pâ=â0.005) but not with monocytic subtype of AML. Sixteen patients had isolated focal basilar airspace opacities, unilateral (nâ=â13) or bilateral (nâ=â3), while 16 patients had bilateral diffuse opacities, interstitial (nâ=â12) or airspace and interstitial (nâ=â4). Two patients had isolated pleural effusion, 2 patients had unilateral midlung airspace opacities, and 6 patients had a combination of focal airspace and diffuse interstitial opacities. Overall, 2 patterns accounted for 75% of abnormal findings: bilateral diffuse opacities tended to be associated with monocytic AML, whereas basilar focal airspace opacities were more frequent in nonmonocytic AML (Pâ<â0.05). Eighteen patients had CT scans, revealing interlobular septal thickening (nâ=â12), airspace (nâ=â11) and ground-glass (nâ=â9) opacities, pleural effusions (nâ=â12), and acute pulmonary embolism (nâ=â2).Hyperleukocytic AML is frequently associated with abnormal chest radiographs, involving mostly focal basilar airspace opacities (more frequent in nonmonocytic AML) or diffuse bilateral opacities. CT scan should be considered broadly due to the suboptimal resolution of radiographs for detecting signs of leukostasis.
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Leucemia Mieloide Aguda/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Leucemia Mieloide Aguda/sangre , Leucocitos , Masculino , Persona de Mediana Edad , Radiografía Torácica , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Patients with acute leukemia can express aberrant markers, defined as antigens that are normally restricted to a different lineage. The reported significance and frequency of these markers is inconclusive. We assessed the frequency and impact of aberrant markers in patients with acute leukemia in a referral institution in Mexico City. METHODS: We included 433 patients, diagnosed and treated between 2005 and 2015 in our institution. RESULTS: Aberrant markers were expressed in 128 patients (29.6%); CD13 and CD33 were the most frequent aberrant markers in patients with acute lymphoblastic leukemia, while CD7 and CD19 were the most frequent in patients with acute myeloid leukemia. In the univariate analysis, the group with aberrant markers had a lower disease-free survival when compared with the aberrant-free group (8 vs. 13 months) (p = 0.03). Aberrant expression of CD10, CD20, and CD33 correlated with a worse outcome in a statistically significant manner. In the multivariate analysis, male gender, lymphoid lineage, secondary leukemia, high risk at diagnosis, and the presence of aberrant markers had a significantly negative impact on disease-free survival. CONCLUSION: The use of more aggressive treatment strategies could be considered in patients with acute leukemia and an aberrant expression of CD10, CD20, and CD33.
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Antígenos CD/sangre , Antígenos de Neoplasias/sangre , Leucemia Mieloide Aguda/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Leucemia Bifenotípica Aguda/sangre , Masculino , México , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
To investigate the expression of interleukin-24 (IL-24) in the children with acute leukemia (AL) and its effect on the apoptosis of bone marrow mononuclear cells (BMMNCs) in vitro. Four groups were assessed: acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), non-leukemia, and healthy groups, 20 children in each group. ELISA was used to measure IL-24 serum level. The bone marrow was taken from patients and controls. BMMNCs were isolated and the DNA was analyzed by glucose electrophoresis. Flow cytometry was used to determine BMMNC apoptosis. The serum level of IL-24 in the ALL and AML groups were significantly higher than in the other two groups. There was no statistical difference between ALL and AML groups, either between non-leukemia and healthy groups. BMMNCs were exposed to IL-24 for 48 h, and the apoptotic rate of the group treated with 50 ng/ml IL-24 was obviously higher than that of control group (0 ng/mL). The serum IL-24 level of AL children decreased comparing to non-leukemia and healthy children, indicating that IL-24 can induce BMMNCs apoptosis of AL children in vitro.
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Células de la Médula Ósea/metabolismo , Interleucinas/sangre , Leucemia Mieloide Aguda/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Adolescente , Apoptosis/efectos de los fármacos , Biomarcadores , Células de la Médula Ósea/efectos de los fármacos , Células Cultivadas , Niño , Preescolar , Femenino , Humanos , Interleucinas/farmacología , Leucemia Mieloide Aguda/sangre , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangreRESUMEN
BACKGROUND AND AIMS: Acute leukemia (AL) is a heterogeneous group of diseases characterized by a disorganized clone proliferation of hematopoietic cells. Thymidine kinase (TK) is a cell enzyme involved in DNA synthesis and is considered a cellular proliferation marker in some solid tumors. METHODS: A cross-sectional prospective and comparative study was performed in the Federico Gomez Children's Hospital in Mexico (HIMFG, in Spanish) in 125 samples of patients of the HIMFG with AL and 138 samples of children without leukemia. Serum TK levels were determined for both groups. RESULTS: Of the children with AL, 90 presented B-cell acute lymphoblastic leukemia (B-ALL); 13, T-cell acute lymphoblastic leukemia (T-ALL); and 22, acute myeloid leukemia (AML). A median (m) TK level of 23.7 IU (IQR 17-35.7) was observed in the group without AL and 91 IU (IQR 98-392) in the AL group. This difference was statistically significant (p <0.0001). When analyzing TK levels according to the type of leukemia, the m was as follows: 68 IU (IQR 35-118) for B-ALL, 470 IU (IQR 88-750) for AML, and 1678 IU (IQR 288-2108) for T- ALL. CONCLUSION: TK is an enzyme showing heterogeneous levels in B-ALL although it is significantly increased in 90% of patients with T-ALL and AML.
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Leucemia Mieloide Aguda/sangre , Leucemia-Linfoma Linfoblástico de Células T Precursoras/sangre , Timidina Quinasa/sangre , Adolescente , Biomarcadores/sangre , Línea Celular , Proliferación Celular , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Leucemia Mieloide Aguda/patología , Masculino , México , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Estudios ProspectivosRESUMEN
The present study aimed to explore the changes in serum endostatin and fibroblast growth factor 19 (FGF-19) in acute myeloid leukemia patients, and to determine their effects on chemotherapeutic sensitivity. Sixty acute myeloid leukemia patients and 30 healthy controls were included in the study. Patient serum endostatin and FGF-19 levels were measured on admission, and then, standard chemotherapy was administered. The patients were divided into 2 groups according to chemotherapeutic effects: 21 patients in the chemotherapeutic sensitivity group (complete remission + partial remission) and 39 in the chemotherapeutic resistance group (no remission + degradation). A receiver operating characteristic (ROC) curve was used to analyze the relationship of serum endostatin and FGF-19 levels with chemotherapeutic sensitivity in acute myeloid leukemia patients. The levels of serum endostatin and FGF-19 in acute myeloid leukemia patients before chemotherapy were significantly higher than those in the control group. Moreover, these levels significantly decreased after chemotherapy (P < 0.01). The levels of serum endostatin and FGF-19 in the chemotherapeutic sensitivity group were lower than those in the chemotherapeutic resistance group, both before and after chemotherapy (P < 0.05 and P < 0.01, respectively). ROC curve analysis showed that the predictive values of endostatin and FGF-19 were good, and there was no significant difference between these results. In conclusion, serum endostatin and FGF-19 can be used as predictors of chemotherapeutic sensitivity for acute myeloid leukemia patients, and may be important for determining prognosis.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Endostatinas/sangre , Factores de Crecimiento de Fibroblastos/sangre , Leucemia Mieloide Aguda/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores Farmacológicos/sangre , Estudios de Casos y Controles , Citarabina/uso terapéutico , Daunorrubicina/uso terapéutico , Resistencia a Antineoplásicos/genética , Endostatinas/genética , Femenino , Factores de Crecimiento de Fibroblastos/genética , Expresión Génica , Harringtoninas/uso terapéutico , Homoharringtonina , Humanos , Idarrubicina/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Inducción de Remisión , Resultado del TratamientoRESUMEN
The familial acute myeloid leukemia related factor gene (FAMLF) was previously identified from a familial AML subtractive cDNA library and shown to undergo alternative splicing. This study used real-time quantitative PCR to investigate the expression of the FAMLF alternative-splicing transcript consensus sequence (FAMLF-CS) in peripheral blood mononuclear cells (PBMCs) from 119 patients with de novo acute leukemia (AL) and 104 healthy controls, as well as in CD34+ cells from 12 AL patients and 10 healthy donors. A 429-bp fragment from a novel splicing variant of FAMLF was obtained, and a 363-bp consensus sequence was targeted to quantify total FAMLF expression. Kruskal-Wallis, Nemenyi, Spearman's correlation, and Mann-Whitney U-tests were used to analyze the data. FAMLF-CS expression in PBMCs from AL patients and CD34+ cells from AL patients and controls was significantly higher than in control PBMCs (P < 0.0001). Moreover, FAMLF-CS expression in PBMCs from the AML group was positively correlated with red blood cell count (rs =0.317, P=0.006), hemoglobin levels (rs = 0.210, P = 0.049), and percentage of peripheral blood blasts (rs = 0.256, P = 0.027), but inversely correlated with hemoglobin levels in the control group (rs = -0.391, P < 0.0001). AML patients with high CD34+ expression showed significantly higher FAMLF-CS expression than those with low CD34+ expression (P = 0.041). Our results showed that FAMLF is highly expressed in both normal and malignant immature hematopoietic cells, but that expression is lower in normal mature PBMCs.
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Secuencia de Consenso/genética , Células Madre Hematopoyéticas/citología , Leucemia Mieloide Aguda/genética , Proteínas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Empalme Alternativo , Recuento de Células Sanguíneas , Estudios de Casos y Controles , Niño , Análisis Mutacional de ADN , Femenino , Humanos , Leucemia Mieloide Aguda/sangre , Masculino , Persona de Mediana Edad , Embarazo , Isoformas de Proteínas/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Valores de Referencia , Transcripción Reversa , Estadísticas no Paramétricas , Adulto JovenRESUMEN
PURPOSE: MiRNA expression profiles previously showed the higher expression of microRNA(miR)-335 in bone marrow samples of pediatric acute myeloid leukemia (AML) patients than normal controls. Our aim was to investigate associations of miR-335 expression with tumor progression and prognosis in pediatric AML. METHODS: Real-time quantitative PCR was performed to detect the expression of miR-335 in bone marrow mononuclear cells and serum obtained from patients with pediatric AML and healthy controls. RESULTS: Expression levels of miR-335 in the bone marrow and serum of pediatric AML patients were both significantly higher than those in normal controls (both P < 0.001). Then, high serum miR-335 level occurred more frequently in French-American-British classification subtype M7 subtype than in other subtypes (P = 0.03). The expression of serum miR-335 in pediatric AML patients with unfavorable karyotypes was also significantly higher than those in intermediate and favorable groups (P = 0.008). Moreover, high serum miR-335 level was markedly associated with shorter relapse-free and overall survivals (both P < 0.001) of patients with pediatric AML. Furthermore, the multivariate analysis identified the serum miR-335 and cytogenetics risk as independent prognostic factors for both relapse-free and overall survivals. More importantly, the prognostic relevance of serum miR-335 expression was more obvious in the subgroup of patients with intermediate-risk cytogenetics. CONCLUSION: Our data offer the convincing evidence for the first time that serum miR-335 level may be markedly and consistently increased in pediatric AML patients. Serum miR-335 may serve as a promising marker for monitoring the progression and predicting the clinical outcome of patients with this disease.
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Leucemia Mieloide Aguda/sangre , Leucocitos Mononucleares/metabolismo , MicroARNs/sangre , Adolescente , Médula Ósea/patología , Estudios de Casos y Controles , Niño , Preescolar , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Cariotipo , Leucemia Mieloide Aguda/clasificación , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Tasa de Supervivencia , Regulación hacia ArribaRESUMEN
Introducción: la recuperación temprana de linfocitos es un factor pronóstico que está relacionado con una mayor supervivencia libre de eventos y supervivencia global en pacientes sometidos a trasplante hematopoyético. Objetivo: determinar el valor pronóstico del recuento absoluto de linfocitos (RAL). Métodos: se realizó un estudio observacional analítico, transversal, ambispectivo, en pacientes pediátricos con hemopatías malignas trasplantados en el Instituto de Hematología e Inmunología de La Habana, Cuba, entre 1986 y 2008. Se estudiaron 36 pacientes: 15 con leucemia linfoide aguda, 13 con leucemia mieloide aguda, 6 con leucemia mieloide crónica y 2 con linfoma no hodgkiniano. Veintitrés trasplantes fueron autólogos y 13 alogénicos; 22 de médula ósea y 14 de sangre periférica. Resultados : de los trasplantes antólogos, el 60,9 por ciento alcanzó un RAL el día + 15 (RAL-15) = 500 x mm3, mientras en los alogénicos este se alcanzó en el 53,8 por ciento. La sangre periférica tuvo un RAL-15 mayor que la médula ósea y se obtuvo en el 78,6 por ciento y el 45,4 por ciento de los enfermos, respectivamente (p = 0.049). Los factores pronósticos asociados a una peor supervivencia global fueron la sepsis (p <0.001), el RAL-15 < 500 x mm3 ( p= 0.001) y la recaída (p = 0.03). Las curvas de Kapplan-Meier mostraron una mejor supervivencia global y libre de eventos a los cinco años, en los pacientes con RAL-15 = 500 x mm3 (85 por ciento vs 15 por ciento; p <0.001). Conclusiones: el RAL-15 = 500 x mm3 es una herramienta simple y útil para predecir un mejor resultado en pacientes pediátricos sometidos a trasplante hematopoyético(AU)
Introduction: early lymphocyte recovery is a prognostic factor related to a higher event-free survival and overall survival in patients who have received hematopoietic transplantation. Objective: eo determine the prognostic value of absolute lymphocyte count (ALC). Method: a study in pediatric patients with hematological malignancies transplanted at the Institute of Hematology and Immunology from 1986 to 2011 was performed. The study group included 36 patients: 15 with acute lymphoid leukemia, 13 with acute myeloid leukemia, 6 with chronic myeloid leukemia and 2 with non Hodgkin lymphoma. Twenty transplants were autologous and 13 allogeneic. As stem cell source, bone marrow was used in 22 patients and peripheral blood in 14. Results : 60,9 percent of the autologous transplants reached an absolute lymphocyte count = 500 x mm3 on day 15 (ALC-15), whereas in the allogeneic this was achieved in 53,8 percent. Peripheral blood had a higher ALC-15 than bone marrow, 78,6 percent and 45,4 percent, respectively (p = 0.049). Prognostic factors associated to worse overall survival were sepsis (p <0.001), ALC-15 <500 x mm3 (p = 0.001) and relapse (p = 0.03). Kapplan-Meier curves showed better overall survival and event-free survival after five years in patients with ALC-15 = 500 x mm3 (85 percent vs. 15 percent, p <0.001). Conclusions: the ALC-15 = 500 x mm3 is a simple and useful tool to predict a better outcome in pediatric patients undergoing hematopoietic transplantation(AU)
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Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Adolescente , Trasplante Autólogo/métodos , Trasplante Homólogo/métodos , Trasplante de Médula Ósea/métodos , Trasplante de Células Madre de Sangre Periférica/métodos , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Leucemia Mieloide Aguda/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Linfoma no Hodgkin/sangre , Pronóstico , Recuento de Linfocitos/métodos , Estudios Transversales , Estudios Observacionales como AsuntoRESUMEN
Introducción: la recuperación temprana de linfocitos es un factor pronóstico que está relacionado con una mayor supervivencia libre de eventos y supervivencia global en pacientes sometidos a trasplante hematopoyético. Objetivo: determinar el valor pronóstico del recuento absoluto de linfocitos (RAL). Métodos: se realizó un estudio observacional analítico, transversal, ambispectivo, en pacientes pediátricos con hemopatías malignas trasplantados en el Instituto de Hematología e Inmunología de La Habana, Cuba, entre 1986 y 2008. Se estudiaron 36 pacientes: 15 con leucemia linfoide aguda, 13 con leucemia mieloide aguda, 6 con leucemia mieloide crónica y 2 con linfoma no hodgkiniano. Veintitrés trasplantes fueron autólogos y 13 alogénicos; 22 de médula ósea y 14 de sangre periférica. Resultados : de los trasplantes antólogos, el 60,9 por ciento alcanzó un RAL el día + 15 (RAL-15) = 500 x mm3, mientras en los alogénicos este se alcanzó en el 53,8 por ciento. La sangre periférica tuvo un RAL-15 mayor que la médula ósea y se obtuvo en el 78,6 por ciento y el 45,4 por ciento de los enfermos, respectivamente (p = 0.049). Los factores pronósticos asociados a una peor supervivencia global fueron la sepsis (p <0.001), el RAL-15 < 500 x mm3 ( p= 0.001) y la recaída (p = 0.03). Las curvas de Kapplan-Meier mostraron una mejor supervivencia global y libre de eventos a los cinco años, en los pacientes con RAL-15 = 500 x mm3 (85 por ciento vs 15 por ciento; p <0.001). Conclusiones: el RAL-15 = 500 x mm3 es una herramienta simple y útil para predecir un mejor resultado en pacientes pediátricos sometidos a trasplante hematopoyético
Introduction: early lymphocyte recovery is a prognostic factor related to a higher event-free survival and overall survival in patients who have received hematopoietic transplantation. Objective: eo determine the prognostic value of absolute lymphocyte count (ALC). Method: a study in pediatric patients with hematological malignancies transplanted at the Institute of Hematology and Immunology from 1986 to 2011 was performed. The study group included 36 patients: 15 with acute lymphoid leukemia, 13 with acute myeloid leukemia, 6 with chronic myeloid leukemia and 2 with non Hodgkin lymphoma. Twenty transplants were autologous and 13 allogeneic. As stem cell source, bone marrow was used in 22 patients and peripheral blood in 14. Results : 60,9 percent of the autologous transplants reached an absolute lymphocyte count = 500 x mm3 on day 15 (ALC-15), whereas in the allogeneic this was achieved in 53,8 percent. Peripheral blood had a higher ALC-15 than bone marrow, 78,6 percent and 45,4 percent, respectively (p = 0.049). Prognostic factors associated to worse overall survival were sepsis (p <0.001), ALC-15 <500 x mm3 (p = 0.001) and relapse (p = 0.03). Kapplan-Meier curves showed better overall survival and event-free survival after five years in patients with ALC-15 = 500 x mm3 (85 percent vs. 15 percent, p <0.001). Conclusions: the ALC-15 = 500 x mm3 is a simple and useful tool to predict a better outcome in pediatric patients undergoing hematopoietic transplantation
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Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Adolescente , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Leucemia Mieloide Aguda/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Linfoma no Hodgkin/sangre , Trasplante Autólogo/métodos , Trasplante Homólogo/métodos , Trasplante de Células Madre de Sangre Periférica/métodos , Trasplante de Médula Ósea/métodos , Estudios Transversales , Estudios Observacionales como Asunto , Pronóstico , Recuento de Linfocitos/métodosRESUMEN
BACKGROUND: Familial platelet disorder with a predisposition to acute myelogenous leukemia (FPD/AML) is an inherited platelet disorder caused by a germline RUNX1 mutation and characterized by thrombocytopenia, a platelet function defect, and leukemia predisposition. The mechanisms underlying FPD/AML platelet dysfunction remain incompletely clarified. We aimed to determine the contribution of platelet structural abnormalities and defective activation pathways to the platelet phenotype. In addition, by using a candidate gene approach, we sought to identify potential RUNX1-regulated genes involved in these defects. METHODS: Lumiaggregometry, α-granule and dense granule content and release, platelet ultrastructure, αIIb ß3 integrin activation and outside-in signaling were assessed in members of one FPD/AML pedigree. Expression levels of candidate genes were measured and luciferase reporter assays and chromatin immunoprecipitation were performed to study NF-E2 regulation by RUNX1. RESULTS: A severe decrease in platelet aggregation, defective αIIb ß3 integrin activation and combined αδ storage pool deficiency were found. However, whereas the number of dense granules was markedly reduced, α-granule content was heterogeneous. A trend towards decreased platelet spreading was found, and ß3 integrin phosphorylation was impaired, reflecting altered outside-in signaling. A decrease in the level of transcription factor p45 NF-E2 was shown in platelet RNA and lysates, and other deregulated genes included RAB27B and MYL9. RUNX1 was shown to bind to the NF-E2 promoter in primary megakaryocytes, and wild-type RUNX1, but not FPD/AML mutants, was able to activate NF-E2 expression. CONCLUSIONS: The FPD/AML platelet function defect represents a complex trait, and RUNX1 orchestrates platelet function by regulating diverse aspects of this process. This study highlights the RUNX1 target NF-E2 as part of the molecular network by which RUNX1 regulates platelet biogenesis and function.
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Trastornos de las Plaquetas Sanguíneas/sangre , Trastornos de las Plaquetas Sanguíneas/complicaciones , Plaquetas/citología , Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/complicaciones , Adenosina Trifosfato/metabolismo , Adulto , Salud de la Familia , Femenino , Perfilación de la Expresión Génica , Humanos , Integrina beta3/metabolismo , Masculino , Subunidad p45 del Factor de Transcripción NF-E2/metabolismo , Linaje , Fenotipo , Fosforilación , Agregación Plaquetaria , Pruebas de Función Plaquetaria , Glicoproteína IIb de Membrana Plaquetaria/metabolismo , Transducción de Señal , Tirosina/metabolismo , Adulto JovenRESUMEN
Se trata de primigesta de 18 años, etnia wayuu, con amenorrea de 30,5 semanas, quien acude en condiciones clínicas de cuidado por presentar disnea acentuada desde hace una semana. El examen físico demostraba palidez cutánea marcada, hiperplasia gingival, soplo holosistólico grado I, taquisfigmia, murmullo vesicular abolido en ambas bases pulmonares con crepitantes bilaterales, abdomen globoso, útero grávido, AU: 27 cm, feto cefálico activo, tacto sin modificaciones. Presenta anemia, marcada leucocitosis, hipoproteinemia, elevación de LDH, y patrón de consolidación bibasal en radiografía pulmonar. Ingresa con diagnóstico de embarazo simple pretérmino, neumonía bilateral, enfermedad linfoproliferativa, y sepsis (?); durante su evolución presenta alteración en el perfil biofísico fetal y hemodinámico, practicándose cesárea segmentaria debido a oligoamnios y sufrimiento fetal agudo. Se obtiene neonato pretérmino, el cual ingresa por prematuridad, sepsis neonatal y enfermedad de membrana hialina. Frotis de sangre periférica revela leucopenia con predominio de monocitos, trombocitopenia, anisocitosis, hipocromia, y macroplaquetas; mientras que el aspirado de médula ósea presentaba 80 % de infiltración de mieloblastos y alteraciones en la citometría de flujo. Recibe quimioterapia según protocolo BMS y manejo médico de las complicaciones presentadas, fallece durante el puerperio tardío.
Primigravida 18 years, ethnicity Wayuu, with 30.5 weeks of amenorrhea, who went into clinical conditions of care for presenting accentuated dyspnea since a week ago. Physical examination showed marked skin pallor, gingival hyperplasia, holosystolic blow, palpitations, vesicular murmur abolished in lungs bases with bilateral crackles. Abdomen with graves uterus, height 27cm, and cephalic active fetus; vaginal touch unchanged. Presents anemia, marked leukocytosis, hypoproteinaemia, elevated LDH, and pattern of consolidation at lungs radiographers. She is admitting with diagnosed of preterm pregnancy, bilateral pneumonia, lymphoproliferative disease, and sepsis (?); during its evolution presents impaired fetal biophysical profile and hemodynamic, practised caesarean operation due to oligoamnios and acute fetal distress. Obtained preterm infant, who was admitted because of prematurity, neonatal sepsis and hyaline membrane disease. Peripheral blood smear reveals predominantly monocytes leukopenia, thrombocytopenia, anisocitosis, hipocromia and macroplaquets. While the bone marrow aspirate showed 80 % of infiltration mieloblasts cells and alterations in the cytometry of flow. Receives chemotherapy by protocol BMS and medical management of complications presented, dies during the late puerperium.
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Humanos , Femenino , Embarazo , Adolescente , Complicaciones Neoplásicas del Embarazo/patología , Leucemia Mieloide Aguda/patología , Complicaciones Neoplásicas del Embarazo/sangre , Enfermedades Raras , Resultado Fatal , Leucemia Mieloide Aguda/sangreRESUMEN
Granulocytic sarcoma (GS) is a rare tumor consisting of immature cells of granulocytic lineage. It is also called chloroma, referring to the green color of the tumor caused by high levels of myeloperoxidase in the cells. GS is often associated with acute myeloblastic leukemia. We report the case of a 4-year-old boy with a diagnosis of acute myeloblastic leukemia. Abdominal ultrasonography demonstrated a solid, vascularized, heterogeneous, polypoid formation involving the posterior wall of the bladder. Further studies confirmed the etiology of the tumor. On control ultrasonography, a marked decrease in tumor size 15 days after treatment was revealed. We describe the imaging findings in this patient and review the literature about this infrequent entity. Although imaging findings are not specific and considering that extramedullary involvement in leukemia is very sensitive to treatment, inclusion of GS in the differential diagnosis and awareness of the possible sites of occurrence and imaging features is essential to avoid unnecessary therapeutic measures.
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Leucemia Mieloide Aguda/diagnóstico , Sarcoma Mieloide/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Vejiga Urinaria/diagnóstico por imagen , Preescolar , Diagnóstico Diferencial , Humanos , Leucemia Mieloide Aguda/sangre , Masculino , UltrasonografíaRESUMEN
PURPOSE: Polymorphisms in the ABCB1 gene may influence P-glycoprotein (Pgp) expression and/or activity. Because the population in Brazil is markedly heterogeneous, we analyzed the relationship between ABCB1 polymorphisms and Pgp expression/activity in Brazilian acute myeloid leukemia (AML) patients. METHODS: Acute myeloid leukemia samples from 109 patients were studied. ABCB1 gene variants rs1128503 (C1236T) and rs1045643 (C3435T) were analyzed by PCR-RFLP assay. Pgp expression and Pgp activity were analyzed by flow cytometry. RESULTS: There was a similar distribution of Pgp expression and activity on polymorphisms C1236T, C1236C, and T1236T for exon 12, and C3435T, C3435C, and T3435T for exon 26. An exception was observed in the lowest ratio of mean fluorescence intensity (MFI) median for Pgp expression in the TT genotype for both studied exons, and its correspondence to a low MFI median for Pgp activity. Pgp expression did not show impact on the response to remission induction therapy, but the MFI median of Pgp expression in the remission failure group was higher than that of the complete remission (CR) group of patients (p = 0.04). Overall survival (OS) was significantly influenced by CR (p = 0.0001). Better 5-year OS and 5-year event-free survival rates (p = 0.04 and p = 0.007, respectively) were achieved in patients presenting the genetic variant CC in exon 12 followed by those presenting the variant CT in exon 26 (p = 0.001). CONCLUSIONS: Polymorphisms in the ABCB1 gene and the levels of Pgp expression could be useful to identify prognostic in AML patients.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/biosíntesis , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Brasil , Estudios de Cohortes , Supervivencia sin Enfermedad , Exones , Femenino , Haplotipos , Humanos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/tratamiento farmacológico , Recuento de Leucocitos/métodos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Inducción de Remisión , Resultado del Tratamiento , Adulto JovenRESUMEN
Leukostasis is a relatively uncommon but potentially catastrophic complication of acute myelogenous leukemia (AML). Prompt leukoreduction is considered imperative to reduce the high mortality rate in this condition. Leukapheresis, usually associated with chemotherapy, is an established approach to diminish blast cell counts. We report a single center experience in managing leukostasis with leukapheresis. Fifteen patients with leukostasis of 187 patients with AML (8.02%) followed at our institution were treated with leukapheresis associated with chemotherapy. The procedures were scheduled to be performed on a daily basis until clinical improvement was achieved and WBC counts were significantly reduced. Overall and early mortalities, defined as that occurred in the first 7 days from diagnosis, were reported. A high proportion of our patients with leukostasis (46.66%) had a monocytic subtype AML (M4/M5, according to French-American-British classification). The median overall survival was 10 days, despite a significant WBC reduction after the first apheresis procedure (from 200.7 × 109/L to 150.3 × 109/L). Almost half of patients (7/15) had an early death. Therapeutic leukapheresis, associated or not to chemotherapy, is an effective approach to reduce WBC counts in patients with AML and leukostasis; however, this therapeutic procedure does not appear to change significantly the sombre prognosis observed in the majority of patients with this complication. Other forms of treatment must be found to reduce the high mortality rate related to leukostasis.
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Leucaféresis , Leucemia Mieloide Aguda/complicaciones , Leucostasis/etiología , Leucostasis/terapia , Adulto , Anciano , Femenino , Humanos , Leucemia Mieloide Aguda/sangre , Recuento de Leucocitos , Leucostasis/sangre , Leucostasis/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Insuficiencia del Tratamiento , Adulto JovenRESUMEN
Existe creciente evidencia que apoya la presencia de un perfil de metilación específico para Leucemia Mieloide Aguda (LMA). La metilación de los islotes CpG en las regiones promotoras de los genes supresores de tumores es un importante mecanismo de control epigenético y participa en el silenciamiento transcripcional. Esto puede contribuir a un nuevo entendimiento de la biología de la enfermedad y vislumbrar nuevas oportunidades terapéuticas. Identificar el perfil de metilación de las áreas promotoras de un grupo de genes supresores de tumores; (p15, p16, ESR1, IGSF4, SOCS1, RARB y DAPK), y relacionar el estatus de metilación gen especifica o combinada con diferentes parámetros clínico patológicos. Se utilizaron muestras de sangre o médula ósea obtenidas al momento del diagnóstico de 33 pacientes con LMA, infantil y del adulto, recolectadas entre los años 1997 y 2008 en el Hospital Hernán Henríquez de Temuco. Se evaluó la presencia de hipermetilación mediante una Reacción de Polimerasa en Cadena Metilación Específica (MSP), previa modificación con bisulfito de sodio. La frecuencia de metilación de los pacientes estudiados fue de 88 por ciento, 27 por ciento, 27 por ciento, 21 por ciento, 15 por ciento, 3 por ciento y 0 por ciento para ESR1, RARb, IGSF4, p15, SOCS1, DAPK, y P16, respectivamente. La hipermetilación de P15 y RARb presentó una asociación significativa para una menor supervivencia en forma individual (p=0,03 y p=0,02), y combinada (p=0,002). No se encontraron diferencias significativas entre metilación y los otros parámetros clínicos analizados. Los pacientes con LMA presentan hipermetilación de la región promotora en algunos genes supresores de tumores, afectando negativamente la supervivencia. Esto pudiese eventualmente contribuir al establecimiento de un patrón de metilación determinado con utilidad clínica.
There is growing evidence than acute myeloid leukemia presents a specific methylation profile. The Methylation of CpG islands within gene promoters is a major epigenetic transcriptional control mechanism and plays a critical role in the transcriptional silencing of tumor suppressor genes. This provides new insights into the biology of the disease and it may offer novel therapeutic opportunities. To identify the promoter methylation profile of tumor suppressor genes (p15, p16, ESR1, IGSF4, SOCS1, RARB y DAPK), and to relate the percentage of methylation with clinicopathological features, as age, gender, white cell count, disease classification and survival rates. Bone marrow and peripheral blood samples were collected at diagnosis from 33 patients with acute myeloid leukemia, infants and adult, between 1997 and 2008 from Hernán Henríquez Aravena Hospital, Temuco, Chile. Methylation in the promoter areas of each tumor suppressor gene was analyzed using the mehylation specific polymerase chain reaction (MSP) technique using sodium bisulfite modification. The frequency of hypermethylation among the patient samples was 88 percent, 27 percent, 27 percent, 21 percent, 15 percent, 3 percent and 0 percent for ESR1, RARb, IGSF4, p15, SOCS1, DAPK, and P16 for each one. Methylation was significantly associated with an inferior overall survival (p=0.03 and p=0.02). When both genes are used, inferior survival is even more significant (p=0.002). There is no significant correlation between methylation and clinicopathological features.Patients with AML have hipermetilation at the promoter region of some tumor supressor genes, with a negative effect in the overall survival. This could eventually become part of establishing a characteristical methilation pattern with clinical utility.