Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.000
Filtrar
1.
DNA Cell Biol ; 38(11): 1374-1386, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31599655

RESUMO

This study was conducted using TagSNPs to systematically explore the relationship between ARID5B polymorphisms and the occurrence, clinical characterization, and prognosis of acute myeloid leukemia (AML). A total of 569 unrelated AML patients and 410 healthy individuals from West China were recruited, and ARID5B TagSNPs were genotyped using iMLDR® (improved multiplex ligation detection reaction). It was found that the association of ARID5B polymorphisms with AML was most significant in acute promyelocytic leukemia (APL), and exclusively in males, the mutant alleles of rs6415872, rs2393726, rs7073837, rs10821936, and rs7089424 were found to increase the risk of developing APL in men, the odds ratio (OR) were 1.36, 1.74, 1.45, 1.53, and 1.56 (all p < 0.05), respectively. Haplotype analysis revealed that haplotype [AACCG] increased the risk of male APL with an OR of 1.53 (95% confidence interval: 1.10-2.14, p = 0.012). Besides, there was a strong positive additive interaction between rs6415872 and rs10821936, rs7089424, respectively, and cases attributed to the interaction of rs6415872, rs10821936, and rs7089424 accounted for 100%. Furthermore, ARID5B single nucleotide polymorphisms were found associated with clinical features of AML, and rs6415872 was shown to be an independent prognosis factor in APL patients. Besides, dual luciferase report assay showed that rs6415872 may affect the binding activity of PPARG with ARID5B. ARID5B polymorphisms contribute to male APL risk, clinical feature, and prognosis, suggesting the importance of ARDI5B in AML pathogenesis and development, and the gender and subtype preference may prompt some specific mechanisms of ARID5B. Besides, ARID5B polymorphisms might be a potential prognosis biomarker.


Assuntos
Proteínas de Ligação a DNA/genética , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/genética , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Células HEK293 , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/genética , Leucemia Promielocítica Aguda/epidemiologia , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Prognóstico , Caracteres Sexuais , Análise de Sobrevida
2.
Hematol Oncol ; 37(4): 438-446, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31378958

RESUMO

To determine the incidence, risk factors, and relative survival of acute myeloid leukemia (AML) secondary to myelodysplastic syndrome (MDS) in the Surveillance, Epidemiology, and End Results (SEER) database. Retrospective analysis of all patients with new MDS onset in the SEER-18 database from 2001 to 2013. We identified 36 558 patients with primary MDS. The rate of secondary AML (sAML) was 3.7% among patients 40 years or younger and 2.5% among those older than 40 (P = .039). The median transformation interval was significantly shorter for the younger group (4.04 vs 13.1 mo; P < .001). For both age groups, median overall and cancer-specific survival were significantly longer for patients who did not develop sAML. Although the younger patients survived longer than the older patients, sAML development had a more negative effect on the survival of younger patients. Female sex, age, and World Health Organization (WHO) type MDS with single lineage dysplasia (MDS-SLD) were associated with a decreased risk of sAML for older but not younger patients. Among older patients with MDS, a married status, Black race, female sex, shorter time to sAML, and WHO type MDS-SLD or MDS with ringed sideroblasts were favorable prognostic factors for survival. In the SEER database, the rate of sAML among patients with MDS is lower than that in previous reports, but these patients still have worse survival. Risk assessment should include clinical and demographic factors.


Assuntos
Leucemia Mieloide Aguda/epidemiologia , Síndromes Mielodisplásicas/patologia , Adulto , Linhagem da Célula , Transformação Celular Neoplásica/patologia , Progressão da Doença , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/etiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Programa de SEER , Fatores Socioeconômicos , Estados Unidos/epidemiologia
3.
Pediatr Blood Cancer ; 66(11): e27942, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31423753

RESUMO

BACKGROUND: High survival rates of 80-90% have been reported in recent clinical trials of reduced-intensity chemotherapies for children with acute myeloid leukemia and Down syndrome (AML-DS). However, a certain number of children with AML-DS have complicating comorbidities, including congenital heart disease (CHD), and are therefore ineligible for enrolment in clinical trials. METHODS: We retrospectively analyzed the clinical characteristics and outcomes of children with AML-DS who were excluded from Japanese clinical trials conducted between 2000 and 2015. RESULTS: Twelve children (six males and six females) were identified and were ineligible for CHD (n = 8) and other comorbidities, including hyperleukocytosis complicated with coagulopathy, severe hemophagocytosis, pulmonary fibrosis, and hypoxic-ischemic encephalopathy (n = 1 each). The median age at the diagnosis was 14 months (range, 5 months to 11.5 years). Among all cases, 11 patients were treated with curative intent. Four patients were considered intolerant to intensive chemotherapy and received only low-dose cytarabine-based chemotherapy: three failed to achieve remission and died of disease, while one successfully achieved remission but eventually died of infection. Seven cases underwent regular-intensive chemotherapy for AML-DS: six were alive and in remission; one had relapsed disease. One patient who received the best supportive care died of disease. Finally, six patients remained in continuous complete remission, while six died. The 5-year overall survival rate was 51%. CONCLUSIONS: The prognosis of AML-DS patients who received insufficient treatment due to severe complication was poor. The optimal dose intensity of curative chemotherapy for such cases should be explored.


Assuntos
Síndrome de Down/epidemiologia , Leucemia Mieloide Aguda/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Ensaios Clínicos como Assunto/normas , Comorbidade , Feminino , Predisposição Genética para Doença , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/genética , Humanos , Hipóxia-Isquemia Encefálica/epidemiologia , Lactente , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/genética , Linfo-Histiocitose Hemofagocítica/epidemiologia , Masculino , Seleção de Pacientes , Fibrose Pulmonar/epidemiologia , Estudos Retrospectivos , Falha de Tratamento
4.
Crit Rev Oncol Hematol ; 141: 125-138, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31279288

RESUMO

Internal tandem duplications and tyrosine kinase mutations in the fms-like tyrosine kinase 3 (FLT3) receptor can occur in acute myeloid leukemia (AML) and portend a poor prognosis. Midostaurin, a multikinase inhibitor that targets FLT3, demonstrated a survival benefit in FLT3-mutated AML in combination with front-line chemotherapy. Despite this advancement, the use of FLT3 inhibitors in clinical practice is complicated by significant drug-drug interactions and uncertainty about optimal timing, duration, and sequencing of therapy. As monotherapy, the utility of FLT3 inhibitors was initially limited by incomplete and transient clinical responses and the development of acquired resistance. This led to the development of more potent and selective FLT3 inhibitors designed to overcome common resistance mechanisms. One of these second generation FLT3 inhibitors, gilteritinib, is now FDA-approved for the treatment of relapsed or refractory AML. Now that multiple FLT3 inhibitors are commercially available, it is important to further delineate the role of these agents in the AML population. This review aims to provide a comprehensive overview of the role of FLT3 inhibitors in AML and apply the current literature to clinical practice.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Compostos de Anilina/uso terapêutico , Humanos , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/genética , Mutação , Pirazinas/uso terapêutico , Estaurosporina/análogos & derivados , Estaurosporina/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/genética
5.
Asian Pac J Cancer Prev ; 20(7): 1939-1943, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31350948

RESUMO

Background: Interleukin-10 (IL-10) is a multifunctional cytokine with both immunosuppressive and antiangiogenicfunctions and may have both tumor-promoting and -inhibiting properties. We examined the association between a single nucleotide polymorphism (SNP) in IL-10 -1082G/A (rs1800896) in Sudanese acute myeloid leukemia (AML) patients and to assess the association between polymorphisms in IL-10 -1082G/A (rs1800896) and the hematological profile in Sudanese patients with AML. Methods: A total of 30 patients with acute myeloid leukemia and 30 control subjects were enrolled in this study. Blood samples were collected from all patients in EDTA containing tubes. Genomic DNA was extracted from all blood samples using salting out method. The genotypic variants of IL-10 (-1082G/A) polymorphism were detected by allele specific-PCR. Results: We found that (36.7%) of patients have homogenous GG genotype, (43.3%) have heterogeneous GA genotype and (20.0%) have AA genotype. GA genotype was significantly associated with higher risk of AML compared with the homozygous Genotypes (GG and AA), there is no association between IL-10 (-1082G/A) polymorphism and AML sub-type, gender, age group, mean of hematological parameters. Conclusion: Our study concluded that GA genotype of IL-10 -1082G/A (rs1800896) polymorphism is a risk factor for AML and G allele is insignificantly higher than A allele in AML patient. No association between IL-10 (-1082G/A) polymorphism and AML sub-type, gender, age group, mean of hematological parameters.


Assuntos
Predisposição Genética para Doença , Interleucina-10/genética , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Prognóstico , Fatores de Risco , Sudão/epidemiologia , Adulto Jovem
6.
Medicine (Baltimore) ; 98(28): e16454, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305478

RESUMO

OBJECTIVE: Tobacco smoke contains carcinogens known to damage somatic and germ cells. In this study, we investigated the effect of tobacco smoking on the risk of childhood acute lymphoblastic leukemia (ALL) and myeloid leukemia (AML). METHODS: Information about tobacco smoking exposures of the mother before, during, and after pregnancy was collected via PubMed, Embase, and Web of Science databases through November 5, 2018. We performed to evaluate the association between smoking exposure and the risk of childhood ALL and AML. Study selection, data abstraction, and quality assessment were performed by 2 independent reviewers. Random effects models were used to obtain summary odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Nineteen case-control studies of childhood leukemia (age < 15 years) conducted in 9 countries from 1974 to 2018. Maternal smoking exposures did not a significant association with childhood ALL (OR = 1.004, 95% CI 0.953-1.058, P = .881) and AML (OR = 0.92, 95% CI 0.815-1.038, P = .177) during exposure time windows. However, there was an association with paternal smoking and ALL (OR = 1.15, 95% CI 1.038-1.275, P = .007). Paternal smoking in AML showed there was no association with smoking exposures and childhood AML (OR = 1.133, 95% CI 0.943-1.362, P = .181). Next, maternal daily cigarettes consumption showed no associations with ALL (OR = 1.08, 95% CI 1.000-1.168, P = .051) during pregnancy. No association with maternal daily smoking and AML (OR = 0.909, 95% CI 0.682-1.211, P = .514). Paternal daily cigarettes consumption was associated with increased risks of childhood ALL (OR = 1.200, 95% CI 1.112-1.302, P = .000). The higher consumption of paternal smoking (more than 10 per day) was significantly related to childhood ALL. Paternal daily smoking consumption also was related to AML (OR = 1.242, 95% CI 1.031-1.496, P = .022). CONCLUSION: Maternal smoking before, during, or after pregnancy was not associated with childhood ALL or AML. However, paternal smoking was related to a significantly elevated risk of childhood ALL during pregnancy, but not for AML. Maternal daily smoking consumption was not associated with ALL or AML during pregnancy. The higher consumption of paternal smoking were, the higher the risk of childhood ALL or AML.


Assuntos
Leucemia Mieloide Aguda/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Adolescente , Criança , Feminino , Humanos , Fatores de Risco
7.
Ann Hematol ; 98(9): 2081-2088, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31240471

RESUMO

Few reports analyze the incidence and clinical outcome of invasive fungal disease (IFD) in patients with newly diagnosed acute myeloid leukemia (AML) undergoing intensive chemotherapy, and thus the impact of different antifungal prophylactic regimens remains unclear. We analyze the incidence and clinical outcome of IFD in a large series of adult AML patients undergoing front-line intensive induction and consolidation chemotherapy between 2004 and 2015 in a single institution. Three antifungal prophylaxis regimens were given (2004-2005 oral fluconazole, 2006-2012 intravenous itraconazole, and 2013-2015 voriconazole). Overall, 285 patients and 589 intensive chemotherapy episodes were assessed (47%) (induction courses 47% and consolidation 53%). The median age was 51 years (range, 17-65). We observed 56 (10%) episodes of IFD. According to the EORTC 2008 criteria, IFD was classified as possible (29, 52%), probable (17, 30%), and proven (10, 18%). Possible/probable/proven IFD rate was significantly lower during HiDAC consolidation as compared to any anthracycline-containing chemotherapy courses (2% vs. 11%, P = 0.001), and under voriconazole prophylaxis as compared to itraconazole and fluconazole (6% vs. 11% vs. 15%, P = 0.007), and the multivariate analysis showed that they were independent risk factors. Patients under voriconazole prophylaxis had shorter hospitalization duration and less frequent use of empirical or directed antifungal therapy. In conclusion, IFD was a frequent complication during upfront intensive chemotherapy courses for adult AML patients. This retrospective study shows that voriconazole prophylaxis was feasible and associated with a lower risk of IFD compared with intravenous itraconazole or oral fluconazole schedules.


Assuntos
Antifúngicos/administração & dosagem , Quimioterapia de Consolidação , Infecções Fúngicas Invasivas , Leucemia Mieloide Aguda , Adolescente , Adulto , Idoso , Feminino , Humanos , Incidência , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/prevenção & controle , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
9.
Artigo em Inglês | MEDLINE | ID: mdl-31181608

RESUMO

Acute leukemia is the most common pediatric malignancy. Some studies suggest early-life exposures to air pollution increase risk of childhood leukemia. Therefore, we explored the association between maternal residential proximity to major roadways and risk of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Information on cases with acute leukemia (n = 2030) was obtained for the period 1995-2011 from the Texas Cancer Registry. Birth certificate controls were frequency matched (10:1) on birth year (n = 20,300). Three residential proximity measures were assessed: (1) distance to nearest major roadway, (2) residence within 500 meters of a major roadway, and (3) roadway density. Multivariate logistic regression was used to generate adjusted odds ratios (aOR) and 95% confidence intervals (CI). Mothers who lived ≤500 meters to a major roadway were not more likely to have a child who developed ALL (OR = 1.03; 95% CI: 0.91-1.16) or AML (OR = 0.84; 95% CI: 0.64-1.11). Mothers who lived in areas characterized by high roadway density were not more likely to have children who developed ALL (OR = 1.06, 95% CI: 0.93-1.20) or AML (OR = 0.83, 95% CI: 0.61-1.13). Our results do not support the hypothesis that maternal proximity to major roadways is strongly associated with childhood acute leukemia. Future assessments evaluating the role of early-life exposure to environmental factors on acute leukemia risk should explore novel methods for directly measuring exposures during relevant periods of development.


Assuntos
Poluentes Atmosféricos/análise , Leucemia Mieloide Aguda/epidemiologia , Exposição Materna , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Características de Residência , Emissões de Veículos/análise , Doença Aguda , Adulto , Poluição do Ar , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Razão de Chances , Texas/epidemiologia
10.
Blood Rev ; 36: 70-87, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31101526

RESUMO

Acute myeloid leukemia (AML) is a malignant disorder of the bone marrow which is characterized by the clonal expansion and differentiation arrest of myeloid progenitor cells. The age-adjusted incidence of AML is 4.3 per 100,000 annually in the United States (US). Incidence increases with age with a median age at diagnosis of 68 years in the US. The etiology of AML is heterogeneous. In some patients, prior exposure to therapeutic, occupational or environmental DNA-damaging agents is implicated, but most cases of AML remain without a clear etiology. AML is the most common form of acute leukemia in adults and has the shortest survival (5-year survival = 24%). Curative therapies, including intensive chemotherapy and allogeneic stem cell transplantation, are generally applicable to a minority of patients who are younger and fit, while most older individuals exhibit poor prognosis and survival. Differences in patient outcomes are influenced by disease characteristics, access to care including active therapies and supportive care, and other factors. After many years without therapeutic advances, several new therapies have been approved and are expected to impact patient outcomes, especially for older patients and those with refractory disease.


Assuntos
Leucemia Mieloide Aguda/epidemiologia , Humanos
11.
Am Soc Clin Oncol Educ Book ; 39: 421-432, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31099627

RESUMO

Most patients with newly diagnosed acute myeloid leukemia (AML) are at least age 65 and continue to have short survival, with many patients receiving no specific anti-AML therapy, particularly if they are older than age 75. Although consensus regarding optimal treatment of this growing population is lacking, treatment options are expanding even for the oldest patients. A fundamental question when seeing an older patient with AML is whether to recommend "more intensive" or "less intensive" induction therapy. Existing data can support more intensive treatment strategies for selected older adults, although there is growing evidence to support less intensive therapies as well. Randomized trials to provide clear comparisons between treatment strategies among well-characterized older adult populations are lacking. Reliance on age alone to determine treatment choice is problematic, as "fitness" or "unfitness" varies dramatically among patients of the same chronologic age and remains poorly characterized in existing studies. This article will provide differing perspectives on the "more" versus "less" question, with particular attention to recent drug approvals. Issues relevant to both treatment decision-making in practice and alternative trial design to inform gaps in knowledge will be discussed. Given the heterogeneity, an important conclusion will be that there is unlikely to be a single best approach and that appropriate decision-making requires considerations of many factors specific to individual patients.


Assuntos
Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/terapia , Fatores Etários , Tomada de Decisão Clínica , Ensaios Clínicos como Assunto , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Gerenciamento Clínico , Disparidades em Assistência à Saúde , Humanos , Leucemia Mieloide Aguda/diagnóstico , Prognóstico , Programa de SEER , Resultado do Tratamento
12.
J Nippon Med Sch ; 86(4): 207-214, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31061250

RESUMO

BACKGROUND: Therapeutic outcomes for childhood malignancy have dramatically improved. However, secondary malignancies are a major concern, as they greatly affect the quality of life of survivors. This retrospective study evaluated the cumulative incidence, clinical features, and outcomes of secondary malignancies at Nippon Medical School Hospital. METHODS: We examined data from 275 cases of primary childhood malignancy diagnosed between 1980 and 2014. Information regarding treatment of the primary malignancy, including irradiation dose, site, and cumulative dose of anticancer drugs, was assessed. We also collected data on secondary malignancy, including patient sex, age at diagnosis, malignancy site, time from primary to secondary malignancy, and outcomes. RESULTS: Secondary malignancies developed in 11 patients and included acute myeloid leukemia (AML) (4), meningioma (4), Ewing sarcoma (1), germ cell tumor (1), and malignant parotid gland tumor (1). The primary malignancies included acute lymphoblastic leukemia (ALL) (9), non-Hodgkin lymphoma (1) and brain tumor (1). In 7 of the 9 ALL patients, chemoradiotherapy was the primary treatment. The meningiomas and 1 solid tumor developed within the radiation field. All AMLs and meningiomas developed within 5 years and after 20 years, respectively, of the primary diagnosis. The 10- and 20-year cumulative incidence rates for secondary malignancy in our hospital were 1.9% and 5.8%, respectively. CONCLUSIONS: Our results revealed that the type of secondary malignancy depends on the interval after the end of treatment for primary malignancy. Meningioma, notably, develops many years after completion of primary malignancy treatment. Early detection during long-term follow-up is therefore essential.


Assuntos
Neoplasias Ósseas/epidemiologia , Leucemia Mieloide Aguda/epidemiologia , Neoplasias Meníngeas/epidemiologia , Meningioma/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Sarcoma de Ewing/epidemiologia , Quimiorradioterapia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Lactente , Masculino , Estudos Retrospectivos , Fatores de Tempo
13.
BMC Cancer ; 19(1): 389, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31023266

RESUMO

BACKGROUND: The impact of Tet oncogene family member 2 (TET2) mutations on the prognosis of acute myeloid leukemia (AML) is still controversial. A meta analysis is needed in order to assess the prognostic significance of TET2 mutation in AML. METHODS: Five databases including PubMed, Cochrane, EMBase, China National Knowledge Internet (CNKI) and Wanfang database were retrieved to search studies that investigated the correlation between TET2 mutations and outcomes of AML patients. Pooled hazard ratios (HRs) and odds ratios (ORs) were used to assess the effects of TET2 mutations. RESULTS: Sixteen studies were included. TET2 mutation was an unfavorable prognostic factor for overall survival (OS: HR = 1.386; P < 0.001) and event-free survival (EFS: HR = 1.594; P = 0.002) in patients with AML. For patients under 65 years of age, TET2 mutation predicted an inferior OS (HR = 1.310, P = 0.051) and EFS (HR = 1.429, P = 0.027). For patients with intermediate-risk cytogenetics (IR-AML), mutant TET2 had a significant association with adverse OS (HR = 0.474; P < 0.001). For patients with normal cytogenetics (CN-AML), mutant TET2 also conferred adverse OS (HR = 1.425; P < 0.001) and EFS (HR = 1.450, P < 0.001). Further, among patients with CN-AML, mutant TET2 was associated with inferior OS (HR = 2.034, P < 0.001) and EFS (HR = 2.140, P < 0.001) in the ELN favorable-risk subgroup and an inferior EFS (HR = 1.487; P < 0.001) in the ELN intermediate-Isubgroup. With respect to treatment outcome, TET2 mutation predicted a significantly lower rate of complete remission (CR) in cases with ELN favorable-risk cytogenetics (OR = 0.460, P = 0.011). CONCLUSIONS: TET2 mutation had adverse impacts on survival and treatment response in AML patients and will contribute to risk-stratification, prognosis prediction and therapy guidance.


Assuntos
Proteínas de Ligação a DNA/genética , Leucemia Mieloide Aguda/genética , Prognóstico , Proteínas Proto-Oncogênicas/genética , Adulto , Idoso , China/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Indução de Remissão , Resultado do Tratamento
14.
PLoS One ; 14(4): e0215453, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30998723

RESUMO

BACKGROUND AND OBJECTIVE: The revised World Health Organization classification of 2016 for myeloid neoplasms and acute leukemia added a section of myeloid neoplasms with germline predisposition. The main objective of our study was to evaluate the frequency of hematologic and solid malignancies in the family history of patients with acute myeloid leukemia (AML) by using a systemic pedigree interview. The family history was taken of 50 patients between 24 and 80 years. FINDINGS: 8/50 (16%) patients with AML had family members with hematologic malignancies. 2/50 (4%) patients had family members of first degree with hematologic malignancies. Furthermore in 42/50 (84%) of AML patients solid malignancies were documented in family members of any degree and in 31/50 (62%) in family members of first degree. The most commonly occurring malignancies in our cohort were breast and colorectal cancer. We analyzed the pedigrees for cancer syndromes that can be associated with acute leukemia like Li-Fraumeni syndrome, Lynch syndrome and hereditary breast cancer. 2/50 (4%) patients fulfilled the criteria for familial breast and ovarian cancer from the German consortium and 1/50 (2%) patients fulfilled the Bethesda Guidelines criteria for hereditary nonpolyposis colorectal cancer. No pedigree met the criteria for Li-Fraumeni syndrome. In 29 cases we compared the patient history obtained in the routine work-up with our data. The accuracy of the obtained family history was 23%, outlining that in the clinical routine information about family histories often escapes notice. CONCLUSION: Our study shows that though generally considered a sporadic disease, the presence of hematologic and solid malignancies in the family history of AML patients is relatively high. One should keep in mind that cancer syndromes like hereditary breast cancer are associated with a higher incidence of leukemia. These data are relevant in the context of family donor search for allogeneic stem cell transplantation, genetic counseling and testing as well as cancer prevention.


Assuntos
Neoplasias Hematológicas , Leucemia Mieloide Aguda , Anamnese , Síndromes Neoplásicas Hereditárias , Linhagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/genética , Humanos , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Síndromes Neoplásicas Hereditárias/epidemiologia , Síndromes Neoplásicas Hereditárias/genética
15.
Future Oncol ; 15(16): 1895-1909, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30912462

RESUMO

Aim: We used Adelphi Real World Disease-Specific Programme data to characterize adults with newly diagnosed or relapsed/refractory de novo acute myeloid leukemia (AML). Materials & methods: Community-practice hematologists/oncologists completed patient record forms for their regular AML patients. Patients were invited to complete patient self-completion forms including 3-Level EuroQol 5-Dimensions (EQ-5D-3L) and Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionnaires. Results: Physicians provided patient record forms for 389 patients (339 newly diagnosed, 50 relapsed/refractory); 68 patients completed patient self-completion forms. Mean EQ-5D visual-analog scale and index and FACT-General scores were significantly lower than US population norms (p < 0.0001); health-related quality of life (HRQoL) scores were generally lower than 11 other cancers. Conclusion: HRQoL impairment is grave in AML. Efforts are needed to improve HRQoL in affected patients.


Assuntos
Leucemia Mieloide Aguda/epidemiologia , Qualidade de Vida , Idoso , Comorbidade , Estudos Transversais , Gerenciamento Clínico , Feminino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Vigilância em Saúde Pública , Inquéritos e Questionários , Estados Unidos/epidemiologia
16.
Cancer Epidemiol ; 59: 158-165, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30776582

RESUMO

BACKGROUND: Parental age has been associated with several childhood cancers, albeit the evidence is still inconsistent. AIM: To examine the associations of parental age at birth with acute myeloid leukemia (AML) among children aged 0-14 years using individual-level data from the Childhood Leukemia International Consortium (CLIC) and non-CLIC studies. MATERIAL/METHODS: We analyzed data of 3182 incident AML cases and 8377 controls from 17 studies [seven registry-based case-control (RCC) studies and ten questionnaire-based case-control (QCC) studies]. AML risk in association with parental age was calculated using multiple logistic regression, meta-analyses, and pooled-effect estimates. Models were stratified by age at diagnosis (infants <1 year-old vs. children 1-14 years-old) and by study design, using five-year parental age increments and controlling for sex, ethnicity, birthweight, prematurity, multiple gestation, birth order, maternal smoking and education, age at diagnosis (cases aged 1-14 years), and recruitment time period. RESULTS: Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) derived from RCC, but not from the QCC, studies showed a higher AML risk for infants of mothers ≥40-year-old (OR = 6.87; 95% CI: 2.12-22.25). There were no associations observed between any other maternal or paternal age group and AML risk for children older than one year. CONCLUSIONS: An increased risk of infant AML with advanced maternal age was found using data from RCC, but not from QCC studies; no parental age-AML associations were observed for older children.


Assuntos
Leucemia Mieloide Aguda/epidemiologia , Pais , Adolescente , Adulto , Peso ao Nascer , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Sistema de Registros , Risco , Inquéritos e Questionários , Adulto Jovem
17.
Eur J Haematol ; 102(5): 424-431, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30801819

RESUMO

PURPOSE: The aim of the study was to evaluate the feasibility and the potential effects of the Haematological Home Care (HHC) programme for acute leukaemia (AL) patients, either in active chemotherapy or in the terminal phase of disease. METHODS: We retrospectively assessed a group of AL patients assisted at home in terms of number of hospitalisations, accesses to emergency department and place of death. We also used historical data to evaluate potential effects of HHC. RESULTS: The study group consisted of 44 patients, 36 of whom (82%) required palliative treatment, and eight (18%) had ongoing active chemotherapy. The mean number of hospitalisations was 0.64 (range 0-7) per patient, and the number of emergency department (ED) visits was 0.82 (range 0-4) per patient. Place of death was at home for 51.4% of patients and in hospital for 40.5%. Considering a historical group of 17 patients assisted at home the rate of hospitalisations and ED visits were 2.53 (range 0-9) and one (range 0-3), respectively. Place of death was home and hospital in 6% and 65%, respectively. CONCLUSIONS: Haematological Home Care for AL patients is feasible and has potential positive effects in terms rate of hospitalisations and place of death.


Assuntos
Serviços de Assistência Domiciliar , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Estudos Retrospectivos , Assistência Terminal , Resultado do Tratamento
18.
Cancer ; 125(11): 1886-1897, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30811592

RESUMO

BACKGROUND: Several risk factors have been implicated in acute myeloid leukemia (AML) leukemogenesis. However, the epidemiologic distribution and precise triggers for AML in Canada remain poorly understood. METHODS: In this study, demographic data for AML patients in Canada from 1992 to 2010 were analyzed using 3 independent population-based cancer registries. The AML incidence and mortality rates were examined at the levels of province/territory, city, and forward sortation area (FSA) postal code. RESULTS: In total, 18,085 patients were identified. AML incidence was documented to be 30.61 cases per million individuals per year (95% confidence interval [CI], 30.17-31.06) from 1992 to 2010. Five industrial cities in Ontario were identified where incidence rates were significantly higher than the national average: Sarnia, Sault Ste. Marie, Thunder Bay, St. Catharines, and Hamilton. Analysis at the FSA postal code level identified significant patient clusters of AML in these cities. Specifically, FSA N7V in Sarnia, Ontario had an incidence of 106.81 (95% CI, 70.96-161.86) cases per million individuals per year, which is >3 times higher than the national average. The pollution from local oil refineries and chemical plants in Sarnia may be implicated as a risk factor for AML in that city. Analysis of mortality rates at the province and city levels corroborated the findings from the incidence data. CONCLUSION: These results provide a comprehensive analysis of AML burden in Canada and reveal striking geographic case clustering in industrial Ontario cities and potentially implicate exposure to materials/pollution from these plants as an important risk factor for developing AML in Canada.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Feminino , Humanos , Incidência , Desenvolvimento Industrial , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Mortalidade , Ontário/epidemiologia , Saúde da População Urbana , Adulto Jovem
19.
Pediatr Blood Cancer ; 66(6): e27683, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30803139

RESUMO

BACKGROUND: Information on stage at diagnosis for childhood blood cancers is essential for surveillance but is not available on a population basis in most countries. Our aim was to apply the internationally endorsed Toronto Paediatric Cancer Stage Guidelines to children (<15 years) with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), or non-Hodgkin lymphoma (NHL) and to assess differences in survival by stage at diagnosis. PROCEDURE: Stage was defined by extent of involvement of the central nervous system (CNS) for ALL and AML and using the Ann Arbor and St Jude-Murphy systems for HL and NHL, respectively. The study cohort was drawn from the population-based Australian Childhood Cancer Registry, consisting of children diagnosed with one of these four blood cancers between 2006 and 2014 with follow-up to 2015. Five-year observed survival was estimated from the Kaplan-Meier method. RESULTS: Stage was assigned to 2201 of 2351 eligible patients (94%), ranging from 85% for AML to 95% for ALL, HL, and NHL. Survival following ALL varied from 94% (95% CI = 93%-95%) for CNS1 disease to 89% (95% CI = 79%-94%) for CNS2 (P = 0.07), whereas for AML there was essentially no difference in survival between CNS- (77%) and CNS+ disease (78%; P = 0.94). Nearly all children with HL survived for five years. There was a trend (P = 0.04) toward worsening survival with higher stage for NHL. CONCLUSIONS: These results provide the first population-wide picture of the distribution and outcomes for childhood blood cancers in Australia by extent of disease at diagnosis and provide a baseline for future comparisons.


Assuntos
Doença de Hodgkin/patologia , Leucemia Mieloide Aguda/patologia , Linfoma não Hodgkin/patologia , Estadiamento de Neoplasias/normas , Guias de Prática Clínica como Assunto/normas , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Sistema de Registros/estatística & dados numéricos , Adolescente , Austrália/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Doença de Hodgkin/epidemiologia , Humanos , Lactente , Leucemia Mieloide Aguda/epidemiologia , Linfoma não Hodgkin/epidemiologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia
20.
Blood ; 133(13): 1457-1464, 2019 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-30630862

RESUMO

The prevention of relapse is the major therapeutic challenge in older patients with acute myeloid leukemia (AML) who have obtained a complete remission (CR) on intensive chemotherapy. In this randomized phase 3 study (HOVON97) in older patients (≥60 years) with AML or myelodysplastic syndrome with refractory anemia with excess of blasts, in CR/CR with incomplete hematologic recovery (CRi) after at least 2 cycles of intensive chemotherapy, we assessed the value of azacitidine as postremission therapy with respect to disease-free survival (DFS; primary end point) and overall survival (OS; secondary end point). In total, 116 eligible patients were randomly (1:1) assigned to either observation (N = 60) or azacitidine maintenance (N = 56; 50 mg/m2, subcutaneously, days 1-5, every 4 weeks) until relapse, for a maximum of 12 cycles. Fifty-five patients received at least 1 cycle of azacitidine, 46 at least 4 cycles, and 35 at least 12 cycles. The maintenance treatment with azacitidine was feasible. DFS was significantly better for the azacitidine treatment group (logrank; P = .04), as well as after adjustment for poor-risk cytogenetic abnormalities at diagnosis and platelet count at randomization (as surrogate for CR vs CRi; Cox regression; hazard ratio, 0.62; 95% confidence interval, 0.41-0.95; P = .026). The 12-month DFS was estimated at 64% for the azacitidine group and 42% for the control group. OS did not differ between treatment groups, with and without censoring for allogeneic hematopoietic cell transplantation. Rescue treatment was used more often in the observation group (n = 32) than in the azacitidine maintenance group (n = 9). We conclude that azacitidine maintenance after CR/CRi after intensive chemotherapy is feasible and significantly improves DFS. The study is registered with The Netherlands Trial Registry (NTR1810) and EudraCT (2008-001290-15).


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/epidemiologia , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Indução de Remissão
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA