RESUMEN
Immune reconstitution after hematopoietic stem cell transplantation (HSCT) is a complex and extremely variable process. The Ikaros transcription factor plays an important role in hematopoiesis in several cell lines, especially in the lymphoid lineage. We hypothesized that Ikaros might influence immune reconstitution, and consequently, the risk of opportunistic infections, relapse, and graft versus host disease (GVHD). Samples were collected from the graft and from the peripheral blood (PB) of the recipients 3 weeks after neutrophil recovery. Real-time polymerase chain reaction (RT-PCR) was performed to analyze the absolute and relative Ikaros expression. Patients were divided into two groups, according to Ikaros expression in the graft and in the recipients' PB based on the ROC curves for moderate/severe cGVHD. A cutoff of 1.48 was used for Ikaros expression in the graft, and a cutoff of 0.79 was used for Ikaros expression in the recipients' PB. Sixty-six patients were included in this study. Median age of patients was 52 years (range 16-80 years), 55% of them were male, and 58% of them had acute leukemia. Median follow-up period was 18 months (range 10-43 months). There was no association between Ikaros expression and the risk of acute GVHD, relapse, or mortality. However, a significant association was observed with the risk of chronic GVHD. Higher Ikaros expression in the graft was associated with a significantly higher cumulative incidence (CI) of moderate/severe chronic GVHD according to the National Institute of Health (NIH) classification at two years (54% vs. 15% for patients with lower expression, P = 0.03). A higher Ikaros expression in the recipients' PB 3 weeks after engraftment was also associated with a significantly higher risk of moderate/severe chronic GVHD (65% vs. 11%, respectively, P = 0.005). In conclusion, Ikaros expression in the graft and in the recipients' PB after transplantation was associated with a higher risk of moderate/severe chronic GVHD. Ikaros expression should be evaluated in larger prospective trials as a potential biomarker for chronic GVHD.
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Síndrome de Bronquiolitis Obliterante , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Factor de Transcripción Ikaros , Leucemia Mieloide Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Enfermedad Crónica , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia Mieloide Aguda/etiología , Estudios Prospectivos , Recurrencia , Factor de Transcripción Ikaros/genética , Factor de Transcripción Ikaros/metabolismoRESUMEN
Introduction: Over the years, the Hispanic population living in the United States has consistently shown high incidence rates of childhood acute leukemias (AL). Similarly, high AL incidence was previously observed in Mexico City (MC). Here, we estimated the AL incidence rates among children under 15 years of age in MC during the period 2010-2017. Methods: The Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia conducted a study gathering clinical and epidemiological information regarding children newly diagnosed with AL at public health institutions of MC. Crude age incidence rates (cAIR) were obtained. Age-standardized incidence rates worldwide (ASIRw) and by municipalities (ASIRm) were calculated by the direct and indirect methods, respectively. These were reported per million population <15 years of age; stratified by age group, sex, AL subtypes, immunophenotype and gene rearrangements. Results: A total of 903 AL cases were registered. The ASIRw was 63.3 (cases per million) for AL, 53.1 for acute lymphoblastic leukemia (ALL), and 9.4 for acute myeloblastic leukemia. The highest cAIR for AL was observed in the age group between 1 and 4 years (male: 102.34 and female: 82.73). By immunophenotype, the ASIRw was 47.3 for B-cell and 3.7 for T-cell. The incidence did not show any significant trends during the study period. The ASIRm for ALL were 68.6, 66.6 and 62.8 at Iztacalco, Venustiano Carranza and Benito Juárez, respectively, whereas, other municipalities exhibited null values mainly for AML. Conclusion: The ASIRw for childhood AL in MC is among the highest reported worldwide. We observed spatial heterogeneity of rates by municipalities. The elevated AL incidence observed in Mexican children may be explained by a combination of genetic background and exposure to environmental risk factors.
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Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Preescolar , Ciudades , Femenino , Humanos , Incidencia , Lactante , Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/etiología , Masculino , México/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/genéticaRESUMEN
Obesity affects the prognosis of several types of cancer. However, whether excess body weight is independently associated with adverse outcomes following initial pediatric acute leukemia (AL) treatment is still unclear. We conducted a systematic review and meta-analysis to investigate the impact of overweight/obesity at diagnosis on pediatric AL prognosis following initial treatment by performing an extensive database search up to January 22, 2021. Twenty-three studies were included, providing data for 15689 children with acute lymphoblastic leukemia (ALL) and 2506 children with acute myeloid leukemia (AML). Data from 12 studies were pooled in the meta-analysis. Children with overweight/obesity at diagnosis of ALL had poorer event free-survival (random-effects hazard ratio of 1.44, 95%CI 1.16-1.79, p = 0.0008), but no difference in overall survival (random-effects hazard ratio 1.33, 95%CI 0.77-2.29, p = 0.31) when compared with healthy-weight children. Children with overweight/obesity at diagnosis of AML had no difference in event-free survival (random-effects hazard ratio of 0.88, 95%CI 0.48-1.59, p = 0.66) or overall survival (random-effects hazard ratio 1.40, 95%CI 0.78-2.49, p = 0.26), when compared with healthy-weight children. This systematic review and meta-analysis indicates that overweight/obesity negatively affects the prognosis of children with ALL. Future studies should address the best approach to consider nutritional status in their management.
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Leucemia Mieloide Aguda , Sobrepeso , Niño , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/etiología , Obesidad/complicaciones , Obesidad/diagnóstico , Sobrepeso/complicaciones , PronósticoRESUMEN
Venetoclax is approved for older untreated acute myeloid leukemia (AML) patients. Venetoclax was available prior to approval off-label. We assessed our single-institution off-label experience with venetoclax/azacitidine, comparing outcomes with a clinical trial cohort that administered this regimen at the same institution. Thirty-three untreated AML patients unfit or unwilling to receive induction chemotherapy and prescribed venetoclax/azacitidine off-trial were retrospectively analyzed and compared with 33 patients who received the same therapy on trial. Outcomes were compared, and comparisons were made to a theoretical scenario in which off-trial patients received induction. Digital droplet polymerase chain reaction evaluated measurable residual disease (MRD). Off-trial venetoclax was attainable in nearly all patients for whom this was desired. The complete remission (CR)/CR with incomplete blood count recovery rate was 63.3% for off-trial patients who received treatment and 84.9% for trial patients (P = .081). The median overall survival for off-trial patients who received treatment was 381 days (95% confidence interval [CI], 174, not reached) vs 880 days (95% CI, 384, not reached) for trial patients (P = .041). Prior exposure to hypomethylating agents was associated with worse outcomes. Response rates with venetoclax/azacitidine were not inferior to a theoretical scenario in which patients received induction, and early death rates were less than expected with induction. MRD negativity was achievable. Newly diagnosed AML patients treated in a "real-world" scenario with off-trial venetoclax/azacitidine had inferior outcomes compared with patients treated in the setting of a clinical trial. Additionally, this therapy may be as effective, and less toxic, when compared with induction chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Azacitidina/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Femenino , Estudios de Seguimiento , Pruebas Genéticas , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/etiología , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Neoplasia Residual/diagnóstico , Pronóstico , Inducción de Remisión , Sulfonamidas/administración & dosificación , Resultado del TratamientoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia Mieloide Aguda/etiología , Mieloma Múltiple/patología , Mieloma Múltiple/terapia , Donantes de Tejidos/provisión & distribución , Terapia Combinada , Humanos , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Mieloma Múltiple/inmunología , PronósticoRESUMEN
Germline RUNX1 mutations lead to thrombocytopenia and platelet dysfunction in familial platelet disorder with predisposition to acute myelogenous leukemia (AML). Multiple aspects of platelet function are impaired in these patients, associated with altered expression of genes regulated by RUNX1 We aimed to identify RUNX1-targets involved in platelet function by combining transcriptome analysis of patient and shRUNX1-transduced megakaryocytes (MK). Down-regulated genes included TREM-like transcript (TLT)-1 (TREML1) and the integrin subunit alpha (α)-2 (ITGA2) of collagen receptor α2-beta (ß)-1, which are involved in platelet aggregation and adhesion, respectively. RUNX1 binding to regions enriched for H3K27Ac marks was demonstrated for both genes using chromatin immunoprecipitation. Cloning of these regions upstream of the respective promoters in lentivirus allowing mCherry reporter expression showed that RUNX1 positively regulates TREML1 and ITGA2, and this regulation was abrogated after deletion of RUNX1 sites. TLT-1 content was reduced in patient MK and platelets. A blocking anti-TLT-1 antibody was able to block aggregation of normal but not patient platelets, whereas recombinant soluble TLT-1 potentiated fibrinogen binding to patient platelets, pointing to a role for TLT-1 deficiency in the platelet function defect. Low levels of α2 integrin subunit were demonstrated in patient platelets and MK, coupled with reduced platelet and MK adhesion to collagen, both under static and flow conditions. In conclusion, we show that gene expression profiling of RUNX1 knock-down or mutated MK provides a suitable approach to identify novel RUNX1 targets, among which downregulation of TREML1 and ITGA2 clearly contribute to the platelet phenotype of familial platelet disorder with predisposition to AML.
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Trastornos de las Plaquetas Sanguíneas/genética , Trastornos de las Plaquetas Sanguíneas/metabolismo , Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , Regulación de la Expresión Génica , Integrina alfa2/genética , Leucemia Mieloide Aguda/etiología , Receptores Inmunológicos/genética , Trastornos de las Plaquetas Sanguíneas/sangre , Plaquetas/metabolismo , Susceptibilidad a Enfermedades , Perfilación de la Expresión Génica , Humanos , Leucemia Mieloide Aguda/diagnóstico , Megacariocitos/metabolismo , Mutación , Agregación Plaquetaria , Pruebas de Función Plaquetaria , Unión ProteicaRESUMEN
In Mexico, due to the high rates of diabetes, overweight, and obesity, there has also been noted an increased newborn weight, which may be contributing to the elevated incidence rate of childhood acute leukemia (AL). We conducted a case-control study in public hospitals of Mexico City aimed to know whether a greater weight at birth is associated with a higher risk of developing leukemia. We included incident cases with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) diagnosed between 2010 and 2015. Controls were frequency-matched to the cases by age, sex, and health institution. Logistic regression analysis was performed adjusting risks by child's sex, overcrowding index, birth order, and mother's age at the time of pregnancy. Adjusted odds ratios (aORs) and 95% confidence intervals were calculated. A total of 1455 cases and 1455 controls were included. An evident association between ALL and child's birthweight ≥2500 g was found (aOR 2.06; 95% CI: 1.59, 2.66) and also, in those with birthweight ≥3500 g (aOR 1.19; 95% CI: 1.00, 1.41). In AML patients with birthweight ≥2500 g and ≥3500 g, an aOR of 1.77 (95% CI: 1.07, 2.94) and 1.42 (95% CI: 1.03-1.95) was observed, respectively. No association was noticed with either type of AL and a birthweight ≥4000 g. To sum up, we found a moderate association between not having a low birthweight and an increased risk of acute leukemias. Birthweight ≥3500 g was also a risk factor for both types of leukemia. This suggests that a greater birthweight may increase the risk of acute leukemias in Mexican children.
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Peso al Nacer , Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiología , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Humanos , Lactante , México/epidemiología , Oportunidad Relativa , Vigilancia de la Población , Medición de Riesgo , Factores de RiesgoRESUMEN
BACKGROUND: Acute leukemia is the most common cancer in childhood. Analyzing the spatial distribution of acute leukemia may generate the identification of risk factors. OBJECTIVE: To study the incidence rate of acute leukemia, its geographic distribution, and cluster detection in the metropolitan area of Guadalajara, Mexico. METHODS: We included children under 15 years of age diagnosed with acute leukemia during the period 2010-2014 in the metropolitan area of Guadalajara. Each case was geo-referenced to street level to latitude and longitude coordinates using Quantum Geographic Information System (QGIS). Spatial clusters were found in the location of the acute leukemia cases applying the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm with R statistical software. RESULTS: A total of 269 cases of leukemia were registered, 227 (84%) were acute lymphoblastic leukemia and 42 (16%) acute myeloblastic leukemia. The mean age was 6 ± 4 years. The mean incidence of acute leukemia was 6.44 cases/100,000 inhabitants: El Salto 10.12/100,000, Guadalajara 7.55/100,000, and Tlaquepaque 6.74/100,000. The DBSCAN found three clusters, all located within the municipality of Guadalajara. CONCLUSIONS: The incidence of acute leukemia in our population is higher than that in Canada and the USA. We found three spatial clusters of childhood acute lymphoblastic leukemia in the municipality of Guadalajara, suggesting the presence of local predisposing factors.
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Leucemia Mieloide Aguda/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Adolescente , Algoritmos , Niño , Preescolar , Análisis por Conglomerados , Femenino , Humanos , Incidencia , Leucemia Mieloide Aguda/etiología , Masculino , México/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiología , Factores de RiesgoRESUMEN
PURPOSE: As a desmoplastic reaction, tissue fibrosis played crucial roles in solid tumor progression, chemo-resistance, and consequently heralded poor clinical outcome. Previous studies implied the effects of marrow fibrosis on prognosis for acute lymphoblastic leukemia were disputable. In this study, we aimed to investigate the potential role of bone marrow fibrosis on clinical survival in acute myeloid leukemia (AML) patients. METHODS: Bone marrow fibrosis (evaluated as reticulin fiber density, RFD) in bone marrow sections was evaluated at diagnosis via computer technology. Receiver operating characteristic curve (ROC) was used to analyze the predictive value of RFD for relapse and survival status. Kaplan-Meier method was used to estimate survival rates per subgroup between patients with different RFD. Cox proportional hazard regression was used to model the overall survival. RESULTS: High RFD at diagnosis in bone marrow sections from primary AML might predict early relapse and shorter survival (P = 0.003 and 0.001, respectively). The optimal cutoff value of RFD at diagnosis was determined to be 7.2%. Furthermore, the Kaplan-Meier analysis indicated that patients with high marrow RFD had shorter relapse-free survival (RFS) and overall survival (OS) than patients with low RFD (P = 0.007 and 0.000, respectively). Multivariate analysis suggested that similar with cytogenetics, marrow RFD at diagnosis was an independent prognostic factor for RFS [HR 0.564, 95% confidence interval (CI) 0.338-0.940, P = 0.028] and OS (HR 0.457, 95% CI 0.225-0.929, P = 0.031) in primary AML patients. CONCLUSIONS: Our data suggest that marrow RFD before treatment should be seemed as prognostic factor in primary AML, it may provide valuable clues for developing new targeted therapy.
Asunto(s)
Leucemia Mieloide Aguda/mortalidad , Mielofibrosis Primaria/complicaciones , Adolescente , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mieloide Aguda/etiología , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Mielofibrosis Primaria/mortalidad , Mielofibrosis Primaria/patología , Pronóstico , Curva ROC , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Most children with cancer live in resource-limited countries where malnutrition is often prevalent. We identified the relationship between malnutrition and treatment-related morbidity (TRM), abandonment of therapy, and survival of children with cancer in Nicaragua to better inform targeted nutritional interventions. PROCEDURE: We conducted a retrospective review of patients aged 6 months to 18 years with newly diagnosed acute lymphoblastic leukemia, acute myeloid leukemia (AML), Wilms tumor, Hodgkin lymphoma, or Burkitt lymphoma (BL) who were treated between January 1, 2004, and December 31, 2007 at Children's Hospital Manuel de Jesus Rivera in Managua, Nicaragua. Statistical analysis examined the relations among nutritional status and cancer type, risk category, TRM, and event-free survival (EFS). RESULTS: Sixty-seven percent of patients (189/282) were malnourished at diagnosis. Malnutrition was highest among patients with Wilms tumor (85.7%), BL (75%), and AML (74.3%). A total of 92.2% of patients (225/244) experienced morbidity during the first 90 days. Malnutrition was associated with severe infection (P = 0.033). Severely malnourished patients had ≥grade 3 TRM on more days (P = 0.023) and were more likely to experience severe TRM on >50% of days (P = 0.032; OR, 3.27 [95% CI, 1.05-10.16]). Malnourished patients had inferior median EFS (2.25 vs. 5.58 years; P = 0.049), and abandoned therapy more frequently (P = 0.015). CONCLUSIONS: In Nicaragua, pediatric oncology patients with malnutrition at diagnosis experienced increased TRM, abandoned therapy more frequently, and had inferior EFS. Standardized nutritional evaluation of patients with newly diagnosed cancer and targeted provision of nutritional support are essential to decrease TRM and improve outcomes.
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Linfoma de Burkitt/mortalidad , Enfermedad de Hodgkin/mortalidad , Leucemia Mieloide Aguda/mortalidad , Desnutrición/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Tumor de Wilms/mortalidad , Adolescente , Linfoma de Burkitt/etiología , Linfoma de Burkitt/terapia , Niño , Preescolar , Países en Desarrollo , Femenino , Estudios de Seguimiento , Enfermedad de Hodgkin/etiología , Enfermedad de Hodgkin/terapia , Humanos , Lactante , Neoplasias Renales/etiología , Neoplasias Renales/mortalidad , Neoplasias Renales/terapia , Leucemia Mieloide Aguda/etiología , Leucemia Mieloide Aguda/terapia , Masculino , Desnutrición/fisiopatología , Morbilidad , Estadificación de Neoplasias , Nicaragua , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Tumor de Wilms/etiología , Tumor de Wilms/terapiaRESUMEN
The interaction between the bone marrow microenvironment and malignant hematopoietic cells can result in the protection of leukemia cells from chemotherapy in both myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We, herein, characterized the changes in cytokine expression and the function of mesenchymal stromal cells (MSC) in patients with MDS, AML with myelodysplasia-related changes (MRC), a well-recognized clinical subtype of secondary AML, and de novo AML. We observed a significant inhibitory effect of MDS-MSC on T lymphocyte proliferation and no significant differences in any of the cytokines tested. AML-MSC inhibited T-cell proliferation only at a very low MSC/T cell ratio. When compared to the control, AML-MRCderived MSC presented a significant increase in IL6 expression, whereas de novo AML MSC presented a significant increase in the expression levels of VEGFA, CXCL12, RPGE2, IDO, IL1ß, IL6 and IL32, followed by a decrease in IL10 expression. Furthermore, data indicate that IL-32 regulates stromal cell proliferation, has a chemotactic potential and participates in stromal cell crosstalk with leukemia cells, which could result in chemoresistance. Our results suggest that the differences between AML-MRC and de novo AML also extend into the leukemic stem cell niche and that IL-32 can participate in the regulation of the bone marrow cytokine milieu.
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Microambiente Celular , Leucemia Mieloide Aguda/etiología , Leucemia Mieloide Aguda/metabolismo , Síndromes Mielodisplásicos/etiología , Síndromes Mielodisplásicos/metabolismo , Microambiente Tumoral , Antimetabolitos Antineoplásicos/farmacología , Médula Ósea/patología , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/patología , Estudios de Casos y Controles , Línea Celular , Proliferación Celular , Microambiente Celular/efectos de los fármacos , Microambiente Celular/genética , Microambiente Celular/inmunología , Quimiotaxis/genética , Quimiotaxis/inmunología , Citarabina/farmacología , Citocinas/metabolismo , Femenino , Regulación de la Expresión Génica , Silenciador del Gen , Humanos , Inmunomodulación , Leucemia Mieloide Aguda/patología , Masculino , MicroARNs/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Síndromes Mielodisplásicos/patología , FN-kappa B/metabolismo , Interferencia de ARN , Transducción de Señal , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/inmunologíaRESUMEN
INTRODUCTION: Acute myeloid leukemias represent the second most common childhood leukemia subtype. In Mexico, there are few studies on descriptive epidemiology for this disease. AIMS: To report acute myeloid leukemia incidence for children less than 15 years of age in the Metropolitan Area of the Valley of Mexico for a period of five years (2010-2014) and to analyze whether there are differences in the incidence of acute myeloid leukemia by regions. MATERIAL AND METHODS: A descriptive study was conducted in nine public hospitals in Mexico City. The crude annual average incidence rate and adjusted average annual incidence rate were calculated. RESULTS: A total of 190 patients with diagnosis of de novo acute myeloid leukemia were analyzed. Male sex (57.2%) and acute myeloid leukemia-M3 subtype (25.3%) were more frequent. The adjusted average annual incidence rates for Mexico City and for the Metropolitan Area of the Valley of Mexico were 8.18 and 7.74 per million children under 15 years old, respectively. CONCLUSIONS: It seems that childhood acute myeloid leukemia incidence is increasing in Mexico City, which makes the identification of associated risk factors imperative.
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Leucemia Mieloide Aguda/epidemiología , Adolescente , Niño , Ciudades/epidemiología , Humanos , Incidencia , Lactante , Leucemia Mieloide Aguda/etiología , Masculino , México/epidemiología , Factores de Riesgo , Distribución por SexoRESUMEN
Secondary acute myeloid leukemia is a very rare complication in patients with solid organ transplantation. We report a 62 years old female who received a right single lung allograft for idiopathic pulmonary fibrosis. Her immunosuppression scheme consisted in prednisone, azathioprine, and tacrolimus. Two years after the transplantation, she presented with progressive pancytopenia. Bone marrow aspiration was informed as a M4 acute myeloid leukemia, confirmed by flow cytometry. Cytogenetic study was complex, including alterations in chromosome 5. A secondary acute myeloid leukemia was diagnosed. The patient developed nosocomial pneumonia and died a few days after the diagnosis, without specific treatment. The pathogenesis of acute myeloid leukemia is probably related to the intensive exposure to immunosuppressant, especially azathioprine, in these patients.
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Inmunosupresores/efectos adversos , Leucemia Mieloide Aguda/etiología , Trasplante de Pulmón/efectos adversos , Azatioprina/efectos adversos , Médula Ósea/patología , Cromosomas Humanos Par 5 , Resultado Fatal , Femenino , Humanos , Leucopenia/complicaciones , Persona de Mediana Edad , Pancitopenia/complicaciones , Tacrolimus/efectos adversosRESUMEN
Anthracycline antibiotics are an effective therapy for a variety of neoplastic diseases. Dilated cardiomyopathy is a known risk of their use. Because of the risk of new or recurrent neoplasm with immunosuppression transplantation is often delayed. Our patient developed early cardiomyopathy with congestive heart failure 3 months after completion of chemotherapy. Given the severity of her cardiac symptoms the decision was made to proceed with heart transplantation in the short term after completion of her chemotherapy. We report the success to 1 year of this decision and discuss the implications of her genetic and oncologic diagnoses in this clinical scenario.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cardiomiopatía Dilatada/inducido químicamente , Síndrome de Down/complicaciones , Trasplante de Corazón , Leucemia Mieloide Aguda/tratamiento farmacológico , Edad de Inicio , Cardiomiopatía Dilatada/cirugía , Preescolar , Femenino , Humanos , Recién Nacido , Leucemia Mieloide Aguda/etiologíaRESUMEN
OBJECTIVE: To investigate the association between maternal exposure to hair dyes and hair straightening cosmetics (HDSC) during pregnancy and leukemia at an early age (<2yr., EAL). METHODS: A multicenter hospital-based case-control study was carried out in 13 states in Brazil between 1999 and 2007. Mothers of 176 ALL (acute lymphocytic leukemia) and 55 AML (acute myeloid leukemia) cases and 419 controls were enrolled and interviewed. Data on maternal exposure to HDSC occurring 3months before pregnancy, during pregnancy and during breastfeeding were obtained. Data were also gathered on paternal exposure to HDSC before pregnancy. Unconditional logistic regression was performed and odds ratios (OR) on the association between HDSC use and EAL were obtained after adjustment for hormonal intake during pregnancy, maternal age, education, birth weight, and the child skin color. RESULTS: An adjusted OR of 1.78 (95% C.I. 1.13-2.81) was observed between maternal exposure to HDSC in the first trimester of pregnancy and ALL. Regarding AML, an adjusted OR of 2.43 (95% C.I. 1.13-5.22) was found for maternal exposure to HDSC during breastfeeding. No association between maternal exposure to HDSC during pregnancy and ALL or AML was observed in children with MLL (Mixed Lineage Leukemia) gene rearrangement. CONCLUSIONS: Results in this study seem to support the hypothesis that maternal exposure to HDSC during pregnancy may be involved in the etiology of leukemia in children under 2years of age.
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Tinturas para el Cabello/efectos adversos , Preparaciones para el Cabello/administración & dosificación , Preparaciones para el Cabello/efectos adversos , Leucemia Mieloide Aguda/etiología , Exposición Materna , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiología , Adulto , Brasil , Lactancia Materna , Estudios de Casos y Controles , Femenino , Humanos , Lactante , Leucemia Bifenotípica Aguda/etiología , Leucemia Bifenotípica Aguda/genética , Modelos Logísticos , Masculino , Oportunidad Relativa , Embarazo , Primer Trimestre del Embarazo , Efectos Tardíos de la Exposición Prenatal , Adulto JovenAsunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Lactante , Preescolar , Niño , Aberraciones Cromosómicas , Análisis Citogenético , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/etiología , Leucemia Mieloide Aguda/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/congénito , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/genéticaRESUMEN
As síndromes mielodisplásicas (SMD) se caracterizam por terem uma hematopoese displásica, citopenias e pelo risco de progressão para leucemia mielóide aguda. O diagnóstico baseia-se na clínica e nos achados citomorfológicos da medula óssea (MO) e citogenéticos. Na fase inicial ou quando a MO é hipocelular o diagnóstico é difícil e a citogenética frequentemente é normal. A imunofenotipagem (IMF) tem sido cada vez mais utilizada nos casos de SMD em adultos e pouco explorada na SMD pediátrica. Os nossos objetivos foram: estudar os casos de SMD e doenças correlatas (LMA relacioanda à SMD: LMA-rMD; leucemia mielomonocítica crônica: LMMC e leucemia mielomonocítica juvenil: LMMJ) em adultos e crianças, associando os dados clínicos e laboratoriais aos obtidos pela IMF, que utilizou um painel de anticorpos monoclonais para as várias linhagens medulares. No período compreendido entre 2000 e 2010 foram estudados 87 pacientes (64 adultos e 23 crianças) oriundos do HUPE/UERJ e IPPMG/UFRJ e 46 controles (23 adultos e 20 crianças). Todos os doentes realizaram mielograma, biópsia óssea, citogenética, citoquímica e estudo imunofenotípico. Segundo os critérios da OMS 50 adultos foram classificados como SMD, 11 como LMA-rMD e 3 LMMC. Entre as crianças 18 eram SMD, 2 LMA e 3 LMMJ. Os pacientes adultos com SMD foram divididos em alto risco (n=9; AREB-1 e AREB-2) e baixo risco (n=41; CRDU, CRDM, CRDM-SA, SMD-N e SMD-5q). As crianças com SMD em CR (n=16) e AREB (n=2). Anormalidades clonais recorrentes foram encontradas em 22 pacientes adultos e em 7 crianças. Na análise de IMF foi utilizada a metodologia da curva ROC para a determinação dos valores de ponto de corte a fim de identificar os resultados anormais dos anticorpos monoclonais nos pacientes e nos controles, permitindo determinar a sensibilidade e especificidade desses em cada linhagem. A IMF foi adequada para a análise em todos os pacientes e 3 ou mais anormalidades foram encontradas. A associação da IMF...
Myelodysplastic syndrome (MDS) is characterized by having a dysplastic hematopoiesis, cytopenias and risk of progression to acute myeloid leukemia. The diagnosis is based on clinical and cytomorphologic findings in bone marrow (BM) and cytogenetics. In the initial phase of when the BM is hypocellular, diagnosis is difficult and often with normal karyotype. The flow cytometry immunophenotyping (FCI) analysis has been broadly used in adult MDS cases but is rarely in pediatric MDS. The objectives of this work were: to study MDS cases and correlated diseases (AML with myelodysplasia-related changes; chronic myelomonocytic leukemia - CMML and juvenite myelomonocytic leukemia - JMML) and to correlate laboratorial data to FCI using a panel of monoclonal antibodies for the various marrow lineages in both adult and children. In the period between 2000 and 2010, 87 patients were studied (64 adults and 23 children) coming from HUPE/UERJ and IPPMG/UFRJ and 46 controls (26 adults and 20 children). All patients were submitted to myelogram, bone marrow biopsy, cytogenetic, cytochemistry and immunophenotypic study. According to WHO criteria 50 adults were classified MDS, 12 AML and 3 CMML. Among the children there were 18 MDS, 2 AML, and 3 JMML. MDS adult patients were subdivided into high risk (n=9; RAEB-1 and RAEB-2) and low risk (n=41; RCUD, RCMD-RS, MDS-U and MDS-5q). MDS children were classified as RCC (n=16) and RAEB (n=2). Clonal abnormalities were found in 22 (35%) adult patients and 7 (30%) children. In the analysis of FCI methodology ROC curve was used for determination of cut off abnormalities at monoclonal antibodies in patients and controls which allowed to estimate the sensitivity and specificity of each strain. The FCI was suitable for analysis in all patients and 3 or more abnormalities were found. The association of the FCI increased the sensitivity of morphological analysis in the erythroid lineage from 70 to 97% in adults and from 59 to 86% in children...
Asunto(s)
Humanos , Masculino , Femenino , Niño , Adulto , Citodiagnóstico , Células de la Médula Ósea/citología , Citometría de Flujo/métodos , Citometría de Flujo , Inmunofenotipificación/métodos , Inmunofenotipificación , Leucemia Mieloide Aguda/etiología , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/patología , Leucemia Mielomonocítica Crónica , Leucemia Mielomonocítica Juvenil , Sensibilidad y EspecificidadRESUMEN
Therapy-related myelodysplastic syndrome (t-MDS) and therapy-related acute myelogenous leukemia (t-AML) in patients with acute promyelocytic leukemia (APL) are rare events. The cumulative exposure to chemotherapy with alkylating agents and topoisomerase II inhibitors is associated with t-AML that may develop any time after the completion of the treatment. We report the case of an acquired AML who previously received therapy for APL, after two years of being diagnosed. The diagnosis was established by morphologic findings, membrane markers, cytogenetic studies, and fluorescence in situ hybridization (FISH). To our knowledge this is the first documented case in Puerto Rico of a patient with APL that developed a t-AML without the characteristic chromosomal and morphologic findings of APL.
Asunto(s)
Leucemia Mieloide Aguda/etiología , Leucemia Promielocítica Aguda/tratamiento farmacológico , Neoplasias Primarias Secundarias/etiología , Translocación Genética , Adulto , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cromosomas Humanos Par 15/ultraestructura , Cromosomas Humanos Par 17/ultraestructura , Cromosomas Humanos Par 21/ultraestructura , Cromosomas Humanos Par 3/ultraestructura , Cromosomas Humanos Par 7 , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Daunorrubicina/efectos adversos , Sinergismo Farmacológico , Resultado Fatal , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Promielocítica Aguda/genética , Masculino , Mercaptopurina/administración & dosificación , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Mitoxantrona/administración & dosificación , Mitoxantrona/efectos adversos , Monosomía , Neoplasias Primarias Secundarias/genética , Tretinoina/administración & dosificaciónRESUMEN
OBJECTIVE: To investigate the risk factors associated with childhood acute leukemia (CHAL). METHODS: During a year period 47 prevalent and incidental cases with CHAL and 47 controls (healthy children) were included. They were matched by gender, age (+/- 3 years) and residence area. Sociodemographic, gyneco-obstetric, perinatal features, parents' use of alcohol or smoking, exposure to electromagnetic fields and exposure to pesticides 3 months before and during pregnancy were assessed. Associations were assessed using odds ratios (OR) with 95 % confidence intervals (CI). RESULTS: The average age was 7.2 +/- 4.4 years; 61.7 % were male. An increased OR was found for domestic (OR = 2.1, CI 95 = % 1.5-2.9) or garden (OR = 1.8, IC 95 % = 1.2-2.6) use of pesticides three months before pregnancy. A non-significant frequency was observed with previous fetal death, neonatal jaundice, smoking 3 months before pregnancy, father intake of alcohol, pesticides use during pregnancy at home or garden and living close (< 60 m) to agricultural fields. CONCLUSIONS: The domestic or garden use of pesticides three months before pregnancy may play a role in the etiology of CHAL.