RESUMO
BACKGROUND: Childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has been associated with early-life exposures, including birth by cesarean section (C-section), and a deficit of social exposure (first child). These exposures as proxies for microbiome acquisition in infancy are essential to prime the immune system and restrain later dysregulated immune responses that can trigger ALL in susceptible individuals. We tested risk factors pertaining to immune stimulation that may impact BCP-ALL development. METHODS: Cases comprised 1,126 children (0-12 years) with ALL (BCP-ALL: 78.5%) from the EMiLI study group in Brazil (2002-2020). Age- and sex-matched controls (n = 2,252) were randomly selected from healthy children whose mothers participated in the National Placental and Umbilical Cord Blood Bank donation. Multiple logistic regression was run fitted and adjusted for selected covariates models. RESULTS: C-section delivery was associated with increased risk for ALL [odds ratio (OR) ALL: 1.10; 95% confidence intervals (CI), 1.04-1.15; ORBCP-ALL: 1.09; 95% CI, 1.03-1.14], as well as being the firstborn child. Interaction analysis showed a significant effect of first birth on the observed C-section associations (P < 0.0001). Indeed, high-risk children, namely, firstborn children delivered via C-section were at increased risk for ALL (OR: 2.33; 95% CI, 2.40-4.84) compared with non-first, vaginally born children. An increased risk was found for firstborn children delivered by C-section and non-breastfed with ALL (ORALL: 2.32; 95% CI, 1.27-4.24; ORBCP-ALL: 2.37; 95% CI, 1.18-4.76). CONCLUSIONS: Our observations are in accord with the prediction that exposures determining microbiome composition and adrenal pathway in infancy contribute to the risk of BCP-ALL. IMPACT: These findings encourage the exploration of potential preventive interventions. See related commentary by Wiemels and Gallant, p. 292.
Assuntos
Cesárea , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Feminino , Gravidez , Cesárea/efeitos adversos , Ordem de Nascimento , Placenta , Fatores de Risco , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologiaRESUMO
Acute lymphocytic leukemia is the most common type of cancer in pediatric individuals. Glucose regulated protein (GRP78) is an endoplasmic reticulum chaperone that facilitates the folding and assembly of proteins and regulates the unfolded protein response pathway. GRP78 has a role in survival of cancer and metastasis and cell-surface associated GRP78 (sGRP78) is expressed on cancer cells but not in normal cells. Here, we explored the presence of sGRP78 in pediatric B-ALL at diagnosis and investigated the correlation with bona fide markers of leukemia. By using a combination of flow cytometry and high multidimensional analysis, we found a distinctive cluster containing high levels of sGRP78, CD10, CD19, and CXCR4 in bone marrow samples obtained from High-risk leukemia patients, which was absent in the compartment of Standard-risk leukemia. We confirmed that sGRP78+CXCR4+ blood-derived cells were more frequent in High-risk leukemia patients. Finally, we analyzed the dissemination capacity of sGRP78 leukemia cells in a model of xenotransplantation. sGRP78+ cells emigrated to the bone marrow and lymph nodes, maintaining the expression of CXCR4. Testing the presence of sGRP78 and CXCR4 together with conventional markers may help to achieve a better categorization of High and Standard-risk pediatric leukemia at diagnosis.
Assuntos
Chaperona BiP do Retículo Endoplasmático/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Receptores CXCR4/metabolismo , Adolescente , Animais , Antígenos CD/metabolismo , Linhagem Celular , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Células Neoplásicas Circulantes/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Fatores de RiscoRESUMO
Acute lymphoid leukemia (ALL) is a type of hematological neoplasm that affects the precursor cells of strains B, T and NK, with a higher incidence in the pediatric range. The pathophysiology of ALL is characterized by chromosomal abnormalities and genetic alterations involved in the differentiation and proliferation of lymphoid precursor cells. Despite the lack of information in the literature, it is believed that leukemogenesis originates from a complex interaction between environmental and genetic factors, which combined lead to cellular modifications. Environmental factors have been evaluated as possible predisposing factors in the development of ALL but there are still conflicting results in the world literature. In this context, the aim of the present review is to discuss the major exogenous factors regarding ALL.
Assuntos
Carcinogênese/imunologia , Regulação Leucêmica da Expressão Gênica/imunologia , Interação Gene-Ambiente , Células Progenitoras Linfoides/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Adulto , Linfócitos B/imunologia , Linfócitos B/patologia , Carcinogênese/genética , Carcinogênese/patologia , Diferenciação Celular , Proliferação de Células , Criança , Aberrações Cromossômicas , Citocinas/genética , Citocinas/imunologia , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Células Progenitoras Linfoides/patologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Linfócitos T/imunologia , Linfócitos T/patologiaRESUMO
OBJECTIVE: To investigate the cellular and molecular epidemiology of acute leukemias in vulnerable populations of children and adolescents in Oaxaca de Juarez, Mexico. MATERIAL AND METHODS: Descriptive, cross-sectional and retrospective study, conducted from 2014 to 2018 in which profiles of molecular and immunophenotypic aberrations were investigated in children and adolescents diagnosed with acute leukemia, by evaluating 28 molecular abnormalities by HemaVision-Q28 multiplex RT-PCR kit and standardized EuroFlow Immunophenotyping of bone marrow cells. RESULTS: We included 218 patients, with 82.5% younger than 14 years and 17.5% adolescents. The median age was 9 years and a main peak of incidence was recorded at age of 4 to 5 years. B-cell acute lymphoblastic leukemia was diagnosed in 70.64% of all cases, acute myeloid leukemia was in 22.48%, T-cell acute lymphoblastic leukemia in 6.42%, and mixed lineage acute leukemia in 0.46% of cases. Overall, chromosomal translocations were positive in 29.82% of cases. While 65.31% of patients with acute myeloid leukemia reported aberrancies, only in 18.83% of B-cell acute lymphoblastic leukemia cases genetic abnormalities were obvious. Surprisingly, most prevalent translocations in B-cell acute lymphoblastic leukemia were t(9;22) in 20.7%, followed by t(4;11) in 17.2% and t(6;11) in 13.8%, whereas patients with acute myeloid leukemia showed t(15;17) in 40.6% and t(8;21) in 21.9%. In contrast, an homogeneous expression of t(3;21) and t(6;11) was recorded for T-cell acute lymphoblastic leukemia and mixed lineage acute leukemia cases, respectively. Except for t(1;19), expressed only by pre-B cells, there was no association of any of the studied translocations with differentiation stages of the B-leukemic developmental pathway. CONCLUSION: Our findings identify near 50% of patients with acute lymphoblastic leukemia at debut with high-risk translocations and poor prognosis in B-cell acute lymphoblastic leukemia as well as an unexpected increase of acute myeloid leukemia cases in young children, suggesting a molecular shift that support a higher incidence of poor prognosis cases in Oaxaca.
Assuntos
Biomarcadores Tumorais , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Adolescente , Fatores Etários , Criança , Pré-Escolar , Estudos Transversais , Suscetibilidade a Doenças , Feminino , Frequência do Gene , Rearranjo Gênico , Humanos , Imunofenotipagem , Masculino , México/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Prognóstico , Vigilância em Saúde Pública , Estudos Retrospectivos , Translocação GenéticaRESUMO
Expression of the cell cycle regulatory gene CDK6 is required for Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) cell growth, whereas expression of the closely related CDK4 protein is dispensable. Moreover, CDK6 silencing is more effective than treatment with the dual CDK4/6 inhibitor palbociclib in suppressing Ph+ ALL in mice, suggesting that the growth-promoting effects of CDK6 are, in part, kinase-independent in Ph+ ALL. Accordingly, we developed CDK4/6-targeted proteolysis-targeting chimeras (PROTACs) that inhibit CDK6 enzymatic activity in vitro, promote the rapid and preferential degradation of CDK6 over CDK4 in Ph+ ALL cells, and markedly suppress S-phase cells concomitant with inhibition of CDK6-regulated phospho-RB and FOXM1 expression. No such effects were observed in CD34+ normal hematopoietic progenitors, although CDK6 was efficiently degraded. Treatment with the CDK6-degrading PROTAC YX-2-107 markedly suppressed leukemia burden in mice injected with de novo or tyrosine kinase inhibitor-resistant primary Ph+ ALL cells, and this effect was comparable or superior to that of the CDK4/6 enzymatic inhibitor palbociclib. These studies provide "proof of principle" that targeting CDK6 with PROTACs that inhibit its enzymatic activity and promote its degradation represents an effective strategy to exploit the "CDK6 dependence" of Ph+ ALL and, perhaps, of other hematologic malignancies. Moreover, they suggest that treatment of Ph+ ALL with CDK6-selective PROTACs would spare a high proportion of normal hematopoietic progenitors, preventing the neutropenia induced by treatment with dual CDK4/6 inhibitors.
Assuntos
Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Recombinantes de Fusão/farmacologia , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quinase 6 Dependente de Ciclina/metabolismo , Modelos Animais de Doenças , Ativação Enzimática/efeitos dos fármacos , Perfilação da Expressão Gênica , Genes cdc , Humanos , Camundongos , Estrutura Molecular , Fosforilação , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/uso terapêutico , Resultado do Tratamento , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
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.
Assuntos
Peso ao Nascer , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Humanos , Lactente , México/epidemiologia , Razão de Chances , Vigilância da População , Medição de Risco , Fatores de RiscoRESUMO
OBJECTIVE: Digit ratio (2D : 4D) has been suggested as a biomarker for prenatal hormone activity and has been linked to several types of cancer. This study investigated the possible correlation between 2D : 4D ratios and acute lymphoblastic leukemia. METHODS: A case-control study was performed with Brazilian subjects. Direct measurements of the lengths of index and ring fingers of both hands of patients with acute lymphoblastic leukemia (n = 43) and controls matched by age and gender (n = 86) were obtained by using a digital vernier caliper. Mean ratios between the second and fourth digits were compared. Data were analyzed by Student's t-test with a significance level of 5%. RESULTS: No significant difference was found between the mean digit ratios of the right and left hands between the groups for any analysis (p > 0.05), neither for the whole sample nor for the distribution by gender. CONCLUSIONS: We observed that patients with acute lymphoblastic leukemia do not have a different digit pattern when compared with unaffected individuals, which may suggest that exposure to prenatal sex hormone is similar between groups.
Assuntos
Dedos/anatomia & histologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Idade Gestacional , Humanos , Masculino , Idade MaternaRESUMO
Childhood acute lymphoblastic leukaemia (ALL) with MLL rearrangement (MLL-r) is an aggressive disease still associated with a high mortality rate. Recent investigations have identified co-operating mutations in the RAS pathway and although the functional consequences of these mutations are not yet fully understood, aberrant regulation of RAS pathway signalling at both transcriptional and protein levels is observed. Studies investigating the efficacy of specific inhibitors of this pathway, e.g. MEK-inhibitors, have also achieved encouraging results. In this context, this mini-review summarizes the available data surrounding MLL-r infant ALL with RAS mutation in relation to other well-known features of this intriguing disease.
Assuntos
Rearranjo Gênico , Genes ras , Histona-Lisina N-Metiltransferase/genética , Mutação , Proteína de Leucina Linfoide-Mieloide/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Humanos , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidoresRESUMO
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.
Assuntos
Leucemia Mieloide Aguda/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Adolescente , Algoritmos , Criança , Pré-Escolar , Análise por Conglomerados , Feminino , Humanos , Incidência , Leucemia Mieloide Aguda/etiologia , Masculino , México/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Fatores de RiscoRESUMO
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.
Assuntos
Linfoma de Burkitt/mortalidade , Doença de Hodgkin/mortalidade , Leucemia Mieloide Aguda/mortalidade , Desnutrição/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Tumor de Wilms/mortalidade , Adolescente , Linfoma de Burkitt/etiologia , Linfoma de Burkitt/terapia , Criança , Pré-Escolar , Países em Desenvolvimento , Feminino , Seguimentos , Doença de Hodgkin/etiologia , Doença de Hodgkin/terapia , Humanos , Lactente , Neoplasias Renais/etiologia , Neoplasias Renais/mortalidade , Neoplasias Renais/terapia , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/terapia , Masculino , Desnutrição/fisiopatologia , Morbidade , Estadiamento de Neoplasias , Nicarágua , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Tumor de Wilms/etiologia , Tumor de Wilms/terapiaRESUMO
Introdução: Leucemia é o câncer mais comum em crianças e a principal causa de óbito relacionada ao câncer na infância. A sobrevida das crianças com leucemia tem melhorado de forma significativa, entretanto, ainda permanece abaixo de 50% na maioria dos países com recursos limitados. Objetivo: Descrever o perfil epidemiológico, incidência, mortalidade, sobrevida das leucemias agudas e os fatores de risco para o óbito em crianças e adolescentes com leucemia mieloide aguda (LMA) em Pernambuco. Metodologia: a) coorte retrospectiva com crianças e adolescentes (0-19 anos), a partir das informações do Registro de Câncer de Base populacional (RCBP) do Recife (período de 1998 - 2007). As tendências da incidência e da mortalidade foram avaliadas utilizando-se o método Joinpoint. A sobrevida relativa foi calculada, utilizando-se a tábua completa de mortalidade disponível no Instituto Brasileiro de Geografia Estatística (IBGE) para o Brasil em 2010. b) Foram analisados o risco cumulativo de óbito precoce (até 6 semanas do diagnóstico) e a sobrevida global (SG) e livre de eventos (recidiva, segunda neoplasia ou óbito) pelo método de Kaplan Meier para leucemia promielocítica aguda (LPA), LMA da síndrome de Down (LMA-SD) e outros subtipos (exceto LMASD e LPA) e os fatores preditivos para o óbito, por características do diagnóstico utilizando-se a regressão multivariada de Cox, distintamente para leucemia promielocítica aguda (LPA) e para outros subtipos de LMA a partir de uma coorte de crianças diagnosticadas entre 2000-2014 com LMA e acompanhadas no Instituto de Medicina Integral Prof. Fernando Figueira (IMIP). Resultados: a) o estudo de base populacional envolveu 175 casos. A taxa de incidência para leucemias foi de 41,1/milhão de habitantes menores de 20 anos, com pico de incidência de 78,3/milhão na faixa de 1 a 4 anos....
Introduction Leukemia is the most common cancer in children and the leading cause of cancerrelateddeath in childhood, with a variable incidence worldwide. The survival rates for children with leukemia have significantly improved. However, it remains below 50% in most countries with limited resources. Objective The aim of the study was to describe the epidemiological profile, incidence,mortality, survival, and risk factors for death in children and adolescents with acute myeloid leukemia (AML) in Pernambuco, Brazil. Methodology Two studies were conducted. a) The first study included a retrospective cohort of children and adolescents aged 019 years, based on the data obtained fromthe population-based cancer registry in Recife (19982007). Joinpoint method was used to evaluate the incidence and mortality trends. The relative survival was calculated using the complete mortality table available at the Instituto Brasileiro de Geografia e Estatística for Brazil in 2010. b) The second study included a cohort of children who were diagnosed with AML between 2000 and 2014 and treated at the Instituto de Medicina Integral Prof. Fernando Figueira - IMIP. The cumulative risk ofearly death (until 6 weeks of diagnosis), overall survival (OS), and event-free survival (EFS) considered as recurrence, second neoplasia, or death for acute promyelocytic leukemia (APL), AML with Down syndrome (AML-DS), and other subtypes (except AML-DS and APL) were analyzed using the Kaplan-Meier method. Cox multivariate regression model was used to identify factors predictive of death, by the characteristics of the diagnosis, distinctly for APL and for the othersubtypes of AML...
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidadeRESUMO
Donor-derived malignancies after allogeneic hematopoietic stem cell transplantation and after solid organ transplantation are considered as rare diseases. We have prospectively searched for donor cell leukemia in a 12-year period, in a single institution, in a group of 106 consecutive patients allografted because of leukemia. We have identified seven cases of donor cell leukemia; six were allografted because of relapsed acute lymphoblastic leukemia and one because of paroxysmal nocturnal hemoglobinuria/aplastic anemia. These figures suggest that the real incidence of donor cell leukemia has been underestimated. The six patients with lymphoblastic donor cell leukemia were treated prospectively with a pediatric-inspired combined chemotherapy schedule designed for de novo acute leukemia. A complete response was obtained in three out of six patients with lymphoblastic donor cell leukemia. It is possible to obtain favorable responses in donor cell leukemia patients employing combined chemotherapy. The long-term donor cell leukemia survivors remain as full chimeras and have not needed a second transplant.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Estudos Prospectivos , Doadores de Tecidos , Adulto JovemRESUMO
BACKGROUND: The role of maternal exposures and conditions in the origin of childhood cancer has been a subject of growing interest, but current evidence is inconclusive. CASE PRESENTATION: We present a case detected in a multicenter case-control study evaluating the association between parental risk factors and childhood acute lymphoblastic leukemia (ALL). The patient is a Colombian girl who was diagnosed with ALL-L1 when she was 2 years old. Her mother had been diagnosed with antiphospholipid syndrome before pregnancy and had also been treated with subcutaneous injections of heparin. Other potentially relevant maternal and patient exposures are also reported in this paper. CONCLUSION: We hypothesize that the maternal autoimmune disease could be a contributor in the causality network of the daughter's leukemia. However, the role of other exposures cannot be excluded.
Assuntos
Síndrome Antifosfolipídica/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/terapia , Pré-Escolar , Estudos Clínicos como Assunto , Feminino , Heparina/uso terapêutico , Humanos , Exposição Materna/efeitos adversos , Mães , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Gravidez , Fatores de RiscoRESUMO
OBJECTIVE : To analyze studies that evaluated the role of infections as well as indirect measures of exposure to infection in the risk of childhood leukemia, particularly acute lymphoblastic leukemia. METHODS : A search in Medline, Lilacs, and SciELO scientific publication databases initially using the descriptors “childhood leukemia” and “infection” and later searching for the words “childhood leukemia” and “maternal infection or disease” or “breastfeeding” or “daycare attendance” or “vaccination” resulted in 62 publications that met the following inclusion criteria: subject aged ≤ 15 years; specific analysis of cases diagnosed with acute lymphoblastic leukemia or total leukemia; exposure assessment of mothers’ or infants’ to infections (or proxy of infection), and risk of leukemia. RESULTS : Overall, 23 studies that assessed infections in children support the hypothesis that occurrence of infection during early childhood reduces the risk of leukemia, but there are disagreements within and between studies. The evaluation of exposure to infection by indirect measures showed evidence of reduced risk of leukemia associated mainly with daycare attendance. More than 50.0% of the 16 studies that assessed maternal exposure to infection observed increased risk of leukemia associated with episodes of influenza, pneumonia, chickenpox, herpes zoster, lower genital tract infection, skin disease, sexually transmitted diseases, Epstein-Barr virus, and Helicobacter pylori . CONCLUSIONS : Although no specific infectious agent has been identified, scientific evidence suggests that exposure to infections has some effect on childhood leukemia etiology. .
OBJETIVO : Analisar estudos que avaliaram o papel de infecções e de medidas indiretas de exposição às infecções no risco de leucemia infantil, principalmente da leucemia linfocítica aguda. MÉTODOS : A busca nas bases de dados Medline, Lilacs e SciELO utilizando-se inicialmente os descritores “leucemia infantil” e “infecção” e, posteriormente, pesquisando-se as palavras “leucemia infantil” e “infecção ou doença materna” ou “aleitamento materno” ou “frequência à creche” ou “vacinação” recuperou 62 publicações que atenderam aos seguintes critérios de inclusão: amostra composta por sujeitos com idade inferior ou igual a 15 anos; análise específica de casos diagnosticados com leucemia linfocítica aguda ou todas as leucemias; avaliação de exposição materna ou infantil a infecções (ou medidas indiretas de exposição à infecção) e risco de leucemia. RESULTADOS : Globalmente, os 23 estudos que avaliaram infecções nas crianças suportam a hipótese de que a ocorrência de infecções no início da infância reduz o risco de leucemia, mas existem discordâncias intra e entre estudos. A avaliação por meio das medidas indiretas de exposição à infecção mostrou evidências de redução do risco de leucemia associado principalmente com frequência à creche. Mais de 50,0% dos 16 estudos que avaliaram exposição materna à infecção observaram aumento do risco de leucemia associado com episódios de gripe, pneumonia, varicela, herpes zoster, infecção do trato genital inferior, doença de pele, doenças sexualmente transmissíveis, vírus Epstein-Barr ...
OBJETIVO : Analizar estudios que evaluaron el papel de infecciones y de medidas indirectas de exposición a las infecciones en el riesgo de leucemia infantil, principalmente de la leucemia linfocítica aguda. MÉTODOS : Se realizó búsqueda en las bases de datos Medline, LILACS y SciELO utilizándose inicialmente los descriptores “leucemia infantil” e “infección” y, posteriormente, investigándose las palabras “leucemia infantil” e “infección o enfermedad materna” o “lactancia materna” o “frecuencia en guardería” o “vacunación” recuperó 62 publicaciones que atendieron los siguientes criterios de inclusión: muestra compuesta por individuos con edad inferior o igual a 15 años; análisis específica de casos diagnosticados con leucemia linfocítica aguda o todas las leucemias; evaluación de exposición materna o infantil a infecciones (o medidas indirectas de exposición a la infección) y riesgo de leucemia. RESULTADOS : Globalmente, los 23 estudios que evaluaron infecciones en los niños soportan la hipótesis de que la ocurrencia de infecciones en el inicio de la infancia reduce el riesgo de leucemia, pero existen discordancias intra y entre estudios. La evaluación por medio de las medidas indirectas de exposición a la infección mostró evidencias de reducción de riesgo de leucemia asociado principalmente con frecuencia a la guardería. Más de 50% de los 16 estudios que evaluaron exposición materna a la infección observaron aumento de riesgo de leucemia asociado con episodios de gripe, neumonía, varicela, herpes zoster, infección del tracto genital inferior, enfermedad de la piel, enfermedades sexualmente transmisibles, virus Epstein-Barr (EBV) y Helicobacter pylori. CONCLUSIONES : A pesar ...
Assuntos
Feminino , Humanos , Masculino , Gravidez , Infecções/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Brasil , Aleitamento Materno , Infecções/classificação , Infecções/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/prevenção & controle , Complicações Infecciosas na Gravidez , Fatores de RiscoRESUMO
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.
Assuntos
Tinturas para Cabelo/efeitos adversos , Preparações para Cabelo/administração & dosagem , Preparações para Cabelo/efeitos adversos , Leucemia Mieloide Aguda/etiologia , Exposição Materna , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Adulto , Brasil , Aleitamento Materno , Estudos de Casos e Controles , Feminino , Humanos , Lactente , Leucemia Aguda Bifenotípica/etiologia , Leucemia Aguda Bifenotípica/genética , Modelos Logísticos , Masculino , Razão de Chances , Gravidez , Primeiro Trimestre da Gravidez , Efeitos Tardios da Exposição Pré-Natal , Adulto JovemRESUMO
OBJECTIVE: To analyze studies that evaluated the role of infections as well as indirect measures of exposure to infection in the risk of childhood leukemia, particularly acute lymphoblastic leukemia. METHODS: A search in Medline, Lilacs, and SciELO scientific publication databases initially using the descriptors "childhood leukemia" and "infection" and later searching for the words "childhood leukemia" and "maternal infection or disease" or "breastfeeding" or "daycare attendance" or "vaccination" resulted in 62 publications that met the following inclusion criteria: subject aged ≤ 15 years; specific analysis of cases diagnosed with acute lymphoblastic leukemia or total leukemia; exposure assessment of mothers' or infants' to infections (or proxy of infection), and risk of leukemia. RESULTS: Overall, 23 studies that assessed infections in children support the hypothesis that occurrence of infection during early childhood reduces the risk of leukemia, but there are disagreements within and between studies. The evaluation of exposure to infection by indirect measures showed evidence of reduced risk of leukemia associated mainly with daycare attendance. More than 50.0% of the 16 studies that assessed maternal exposure to infection observed increased risk of leukemia associated with episodes of influenza, pneumonia, chickenpox, herpes zoster, lower genital tract infection, skin disease, sexually transmitted diseases, Epstein-Barr virus, and Helicobacter pylori . CONCLUSIONS: Although no specific infectious agent has been identified, scientific evidence suggests that exposure to infections has some effect on childhood leukemia etiology.
Assuntos
Infecções/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Brasil , Aleitamento Materno , Feminino , Humanos , Infecções/classificação , Infecções/epidemiologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/prevenção & controle , Gravidez , Complicações Infecciosas na Gravidez , Fatores de RiscoAssuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Aberrações Cromossômicas , Análise Citogenética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/congênito , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genéticaRESUMO
BACKGROUND: Epidemiological studies have identified increased risks of leukemia in children living near power lines and exposed to relatively high levels of magnetic fields. Results have been remarkably consistent, but there is still no explanation for this increase. In this study we evaluated the effect of 60 Hz magnetic fields on acute lymphocytic leukemia (ALL) in the State of São Paulo, Brazil. METHODS: This case-control study included ALL cases (n=162) recruited from eight hospitals between January 2003 and February 2009. Controls (n=565) matched on gender, age, and city of birth were selected from the São Paulo Birth Registry. Exposure to extremely low frequency magnetic fields (ELF MF) was based on measurements inside home and distance to power lines. RESULTS: For 24h measurements in children rooms, levels of ELF MF equal to or greater than 0.3microtesla (µT), compared to children exposed to levels below 0.1 µT showed no increased risk of ALL (odds ratio [OR] 1.09; 95% confidence interval [95% CI] 0.33-3.61). When only nighttime measurements were considered, a risk (OR 1.52; 95% CI 0.46-5.01) was observed. Children living within 200 m of power lines presented an increased risk of ALL (OR 1.67; 95% CI 0.49-5.75), compared to children living at 600 m or more of power lines. For those living within 50 m of power lines the OR was 3.57 (95% CI 0.41-31.44). CONCLUSIONS: Even though our results are consistent with the small risks reported in other studies on ELF MF and leukemia in children, overall our results do not provide support for an association between magnetic fields and childhood leukemia, but small numbers and likely biases weaken the strength of this conclusion.
Assuntos
Campos Eletromagnéticos/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Brasil , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Habitação , Humanos , Lactente , Masculino , Razão de ChancesRESUMO
BACKGROUND: Resource-rich countries tend to have a higher incidence of childhood acute lymphoblastic leukemia (ALL), whereas lower rates are seen in more deprived countries. This study describes the incidence of childhood acute leukemia in Brazil, an upper middle-income country, based on data from 16 population-based cancer registries (PBCRs). PROCEDURE: Data were examined from 16 PBCRs in Brazilian cities located in five geographical regions during the period from 1997 to 2004. Incidence rates were analyzed according to gender, age, and type of leukemia. The Wilcoxon test was performed to evaluate for gender-age based difference between by leukemia type. RESULTS: The median age-adjusted incidence rate (AAIR) of leukemia in children aged 0-14 years old was 53.3 per million. A different AAIR was found regarding ALL and myeloproliferative disorders (MPD) that ranged from 24.8 to 76.84 per 1,000,000 children. Manaus, although located in a poor area of Brazil, exhibited the highest AAIR (56.6 per million) of ALL. Goiania had the highest AAIR (24.5 per million) of MPD. The median age-specific incidence rate (ASIR) for the 16 Brazilian PBCRs demonstrated a marked peak in incidence of ALL at age 3 years old, in both genders. CONCLUSIONS: This population-based study of childhood leukemia demonstrates that substantial regional differences exist regarding the incidence of acute leukemia in Brazil, which warrants further ecological study.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Topografia Médica/estatística & dados numéricos , Adolescente , Fatores Etários , Brasil/epidemiologia , Criança , Pré-Escolar , Coleta de Dados , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Sistema de Registros , Fatores Sexuais , Fatores SocioeconômicosRESUMO
Previous epidemiologic studies showed four times increased risk of acute lymphoblastic leukemia (ALL) in children of women with multiple sclerosis (MS). MS shows a risk association with Human leukocyte antigens (HLA)-DRA single nucleotide polymorphism (SNP) rs3135388, which is a proxy marker for DRB1*1501. We examined the relevance of rs3135388 in childhood ALL risk along with two other HLA-DRA SNPs in two case-control groups: 114 cases and 388 controls from South Wales (UK) and 100 Mexican Mestizo cases and 253 controls. We first confirmed the correlation between rs3135388 and DRB1*1501 in HLA-typed reference cell lines. We noted a female-specific risk association in childhood ALL (pooled odds ratio (OR) = 2.6, 95% confidence interval (CI) = 1.5-4.5, Mantel-Haenszel P = 0.0009) similar to the stronger association of DRB1*1501 in females with MS. Examination of an HLA-C 5' flanking region SNP rs9264942, known to correlate with HLA-C expression, showed a protective association in girls (OR = 0.4, 95% CI = 0.2-0.7, Mantel-Haenszel P = 0.0003) similar to the protective HLA-Cw*05 association in MS. In a reference cell line panel, HLA-Cw5 homozygous samples (n = 8) were also homozygous for the minor allele of the SNP. Likewise, the male-specific protective association of interferon-gamma (IFNG) SNP rs2069727 in MS was replicated with the same sex specificity in childhood ALL (OR = 0.6, 95% CI = 0.4-1.0, Mantel-Haenszel P = 0.03). Two other SNPs in superkiller viralicidic activity 2-like and tenascin XB that are markers for systemic lupus erythematosus susceptibility showed female-specific associations but due to linkage disequilibrium with HLA-DRB1*15. Our observations supported the epidemiologic link between MS and childhood ALL and added the sex effect to this connection. It appears that only girls born to mothers with MS may have an increased risk of ALL. Investigating the mechanism of these sex-specific associations may help understand the pathogenesis of MS and ALL.