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1.
Ann Hematol ; 100(1): 261-271, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33067700

RESUMO

We designed a study to describe the incidence of intracranial hemorrhage according to severity and duration of thrombocytopenia and to quantify the associations of platelet transfusions with intracranial hemorrhage in patients with acute leukemia. In this case-control study nested in a cohort of 859 leukemia patients, cases (n = 17) were patients diagnosed with intracranial hemorrhage who were matched with control patients (n = 55). We documented platelet counts and transfusions for seven days before the intracranial hemorrhage in cases and in a "matched" week for control patients. Three measures of platelet count exposure were assessed in four potentially important time periods before hemorrhage. Among these leukemia patients, we observed the cumulative incidence of intracranial hemorrhage of 3.5%. Low platelet counts were, especially in the three to seven days preceding intracranial hemorrhage, associated with the incidence of intracranial hemorrhage, although with wide confidence intervals. Platelet transfusions during the week preceding the hemorrhage were associated with higher incidences of intracranial hemorrhage; rate ratios (95% confidence interval) for one or two platelet transfusions and for more than two transfusions compared with none were 4.04 (0.73 to 22.27) and 8.91 (1.53 to 51.73) respectively. Thus, among acute leukemia patients, the risk of intracranial hemorrhage was higher among patients with low platelet counts and after receiving more platelet transfusions. Especially, the latter is likely due to clinical factors leading to increased transfusion needs.


Assuntos
Hemorragias Intracranianas/epidemiologia , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/terapia , Transfusão de Plaquetas/tendências , Trombocitopenia/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Hemorragias Intracranianas/sangue , Hemorragias Intracranianas/diagnóstico , Leucemia Mieloide Aguda/sangue , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Transfusão de Plaquetas/efeitos adversos , Trombocitopenia/sangue , Trombocitopenia/diagnóstico , Resultado do Tratamento
2.
Ann Hematol ; 99(11): 2547-2553, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32974837

RESUMO

Patients with acute myeloid leukemia (AML) are often exposed to broad-spectrum antibiotics and thus at high risk of Clostridioides difficile infections (CDI). As bacterial infections are a common cause for treatment-related mortality in these patients, we conducted a retrospective study to analyze the incidence of CDI and to evaluate risk factors for CDI in a large uniformly treated AML cohort. A total of 415 AML patients undergoing intensive induction chemotherapy between 2007 and 2019 were included in this retrospective analysis. Patients presenting with diarrhea and positive stool testing for toxin-producing Clostridioides difficile were defined to have CDI. CDI was diagnosed in 37 (8.9%) of 415 AML patients with decreasing CDI rates between 2013 and 2019 versus 2007 to 2012. Days with fever, exposition to carbapenems, and glycopeptides were significantly associated with CDI in AML patients. Clinical endpoints such as length of hospital stay, admission to ICU, response rates, and survival were not adversely affected. We identified febrile episodes and exposition to carbapenems and glycopeptides as risk factors for CDI in AML patients undergoing induction chemotherapy, thereby highlighting the importance of interdisciplinary antibiotic stewardship programs guiding treatment strategies in AML patients with infectious complications to carefully balance risks and benefits of anti-infective agents.


Assuntos
Carbapenêmicos/administração & dosagem , Clostridium difficile , Glicopeptídeos/administração & dosagem , Quimioterapia de Indução , Tempo de Internação , Leucemia Mieloide Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Enterocolite Pseudomembranosa/tratamento farmacológico , Enterocolite Pseudomembranosa/epidemiologia , Feminino , Humanos , Incidência , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/microbiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
3.
Ann Hematol ; 99(12): 2927-2937, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32940726

RESUMO

This study aimed to analyze the factors associated with outcomes of bone marrow transplantation (UR-BMT) or cord blood stem cell transplantation from unrelated donors (UR-CBT). We assessed the time from diagnosis to transplantation among acute myeloid leukemia (AML) patients with intermediate- or poor-risk cytogenetics to identify the potential clinical efficacy of transplantation. We retrospectively analyzed 5331 patients who received UR-BMT or UR-CBT between 2008 and 2017. Patients were divided into four groups according to time from diagnosis to transplantation: (1) UR-BMT and > 5 months (n = 2353), (2) UR-BMT and ≤ 5 months (n = 379), (3) UR-CBT and > 5 months (n = 1494), and (4) UR-CBT and ≤ 5 months (n = 1106). There was no difference in overall survival (OS) for transplantation at ≤5 months and > 5 months in patients with first complete remission for both UR-BMT and UR-CBT, but OS in patients with primary induction failure (PIF) and transplantation at ≤ 5 months was significantly higher in the UR-CBT group compared with that at >5 months (P < 0.001). Multivariate Cox regression analysis also showed that transplantation at >5 months in patients with PIF was an independent predictor of poorer OS. Therefore, UR-CBT at ≤ 5 months after diagnosis is an alternative option for AML patients with PIF.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Análise Citogenética/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Doadores Vivos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Leucemia Mieloide Aguda/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sociedades Médicas , Transplante Homólogo/métodos , Resultado do Tratamento , Adulto Jovem
4.
DNA Cell Biol ; 39(11): 2040-2051, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32915082

RESUMO

As suggested by an increasing amount of evidence, there is alternative splicing (AS) modification within malignancy, which is related to cancer occurrence and development. AS within acute myeloid leukemia (AML) has not yet been systematically analyzed yet. This study analyzed the transcriptomic profiling and corresponding clinical data from AML cases based on The Cancer Genome Atlas (TCGA). In addition, the prediction model, along with the splicing network, was used to analyze the prognosis for AML patients according to the seven different AS event types. Among the 34,984 AS events across the 8830 genes, 2896 AS events were detected among 1905 genes, showing marked correlation with the overall survival of patients. The risk scoring model based on all AS event types was the most efficient in identifying the prognosis for AML patients. Meanwhile, the area under the curve at 1-, 3-, 5-year were 0.852, 0.935, 0.955, respectively. At the same time, the splicing regulating network, which was constituted by 21 splicing factor genes as well as 32 AS events related to survival, was characterized. In conclusion, our predictive model constructed based on the AS events accurately predicts the survival for AML patients. In addition, the network between AS events and splicing factor is established, which may serve as a potential mechanism.


Assuntos
Processamento Alternativo/genética , Leucemia Mieloide Aguda/genética , Proteínas de Neoplasias/genética , Análise de Sobrevida , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes , Humanos , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/patologia , Masculino , Prognóstico , RNA Mensageiro/genética , Transcriptoma/genética
6.
Lancet Oncol ; 21(9): 1201-1212, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32791048

RESUMO

BACKGROUND: Findings of retrospective studies suggest that sorafenib maintenance post-transplantation might reduce relapse in patients with FLT3 internal tandem duplication (FLT3-ITD) acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation. We investigated the efficacy and tolerability of sorafenib maintenance post-transplantation in this population. METHODS: We did an open-label, randomised phase 3 trial at seven hospitals in China. Eligible patients (aged 18-60 years) had FLT3-ITD acute myeloid leukaemia, were undergoing allogeneic haematopoietic stem-cell transplantation, had an Eastern Cooperative Oncology Group performance status of 0-2, had composite complete remission before and after transplantation, and had haematopoietic recovery within 60 days post-transplantation. Patients were randomly assigned (1:1) to sorafenib maintenance (400 mg orally twice daily) or non-maintenance (control) at 30-60 days post-transplantation. Randomisation was done with permuted blocks (block size four) and implemented through an interactive web-based randomisation system. The primary endpoint was the 1-year cumulative incidence of relapse in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02474290; the trial is complete. FINDINGS: Between June 20, 2015, and July 21, 2018, 202 patients were enrolled and randomly assigned to sorafenib maintenance (n=100) or control (n=102). Median follow-up post-transplantation was 21·3 months (IQR 15·0-37·0). The 1-year cumulative incidence of relapse was 7·0% (95% CI 3·1-13·1) in the sorafenib group and 24·5% (16·6-33·2) in the control group (hazard ratio 0·25, 95% CI 0·11-0·57; p=0·0010). Within 210 days post-transplantation, the most common grade 3 and 4 adverse events were infections (25 [25%] of 100 patients in the sorafenib group vs 24 [24%] of 102 in the control group), acute graft-versus-host-disease (GVHD; 23 [23%] of 100 vs 21 [21%] of 102), chronic GVHD (18 [18%] of 99 vs 17 [17%] of 99), and haematological toxicity (15 [15%] of 100 vs seven [7%] of 102). There were no treatment-related deaths. INTERPRETATION: Sorafenib maintenance post-transplantation can reduce relapse and is well tolerated in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation. This strategy could be a suitable therapeutic option for patients with FLT3-ITD acute myeloid leukaemia. FUNDING: None.


Assuntos
Doença Enxerto-Hospedeiro/epidemiologia , Leucemia Mieloide Aguda/tratamento farmacológico , Sorafenibe/administração & dosagem , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , China/epidemiologia , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases , Indução de Remissão , Sorafenibe/efeitos adversos , Sequências de Repetição em Tandem/genética , Transplante Homólogo/efeitos adversos , Adulto Jovem
7.
Ann Hematol ; 99(9): 2201-2203, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32699943
8.
PLoS One ; 15(7): e0235955, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32663229

RESUMO

OBJECTIVES: At any point in time, a person's lifetime health is the number of healthy life years they are expected to experience during their lifetime. In this article we propose an equity-relevant health metric, Health Adjusted Age at Death (HAAD), that facilitates comparison of lifetime health for individuals at the onset of different medical conditions, and allows for the assessment of which patient groups are worse off. A method for estimating HAAD is presented, and we use this method to rank four conditions in six countries according to several criteria of "worse off" as a proof of concept. METHODS: For individuals with specific conditions HAAD consists of two components: past health (before disease onset) and future expected health (after disease onset). Four conditions (acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), schizophrenia, and epilepsy) are analysed in six countries (Ethiopia, Haiti, China, Mexico, United States and Japan). Data from 2017 for all countries and for all diseases were obtained from the Global Burden of Disease Study database. In order to assess who are the worse off, we focus on four measures: the proportion of affected individuals who are expected to have HAAD<20 (T20), the 25th and 75th percentiles of HAAD for affected individuals (Q1 and Q3, respectively), and the average HAAD (aHAAD) across all affected individuals. RESULTS: Even in settings where aHAAD is similar for two conditions, other measures may vary. One example is AML (aHAAD = 59.3, T20 = 2.0%, Q3-Q1 = 14.8) and ALL (58.4, T20 = 4.6%, Q3-Q1 = 21.8) in the US. Many illnesses, such as epilepsy, are associated with more lifetime health in high-income settings (Q1 in Japan = 59.2) than in low-income settings (Q1 in Ethiopia = 26.3). CONCLUSION: Using HAAD we may estimate the distribution of lifetime health of all individuals in a population, and this distribution can be incorporated as an equity consideration in setting priorities for health interventions.


Assuntos
Epilepsia/mortalidade , Nível de Saúde , Leucemia Mieloide Aguda/mortalidade , Mortalidade/tendências , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Anos de Vida Ajustados por Qualidade de Vida , Esquizofrenia/mortalidade , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Epilepsia/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Leucemia Mieloide Aguda/epidemiologia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Esquizofrenia/epidemiologia , Estados Unidos/epidemiologia , Adulto Jovem
9.
Eur J Cancer ; 136: 116-129, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32688206

RESUMO

PURPOSE: The current standard-of-care for front-line therapy for acute myeloid leukaemia (AML) results in short-term and long-term toxicity, but still approximately 40% of children relapse. Therefore, there is a major need to accelerate the evaluation of innovative medicines, yet drug development continues to be adult-focused. Furthermore, the large number of competing agents in rare patient populations requires coordinated prioritisation, within the global regulatory framework and cooperative group initiatives. METHODS: The fourth multi-stakeholder Paediatric Strategy Forum focused on AML in children and adolescents. RESULTS: CD123 is a high priority target and the paediatric development should be accelerated as a proof-of-concept. Efforts must be coordinated, however, as there are a limited number of studies that can be delivered. Studies of FLT3 inhibitors in agreed paediatric investigation plans present challenges to be completed because they require enrolment of a larger number of patients than actually exist. A consensus was developed by industry and academia of optimised clinical trials. For AML with rare mutations that are more frequent in adolescents than in children, adult trials should enrol adolescents and when scientifically justified, efficacy data could be extrapolated. Methodologies and definitions of minimal residual disease need to be standardised internationally and validated as a new response criterion. Industry supported, academic sponsored platform trials could identify products to be further developed. The Leukaemia and Lymphoma Society PedAL/EUpAL initiative has the potential to be a major advance in the field. CONCLUSION: These initiatives continue to accelerate drug development for children with AML and ultimately improve clinical outcomes.


Assuntos
Antineoplásicos , Desenvolvimento de Medicamentos/organização & administração , Leucemia Mieloide Aguda/tratamento farmacológico , Oncologia/organização & administração , Pediatria/organização & administração , Adolescente , Idade de Início , Antineoplásicos/classificação , Antineoplásicos/isolamento & purificação , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Desenvolvimento de Medicamentos/métodos , Desenvolvimento de Medicamentos/normas , Desenvolvimento de Medicamentos/tendências , Europa (Continente)/epidemiologia , Humanos , Agências Internacionais/organização & administração , Agências Internacionais/tendências , Cooperação Internacional , Leucemia Mieloide Aguda/epidemiologia , Oncologia/tendências , Pediatria/tendências , Análise de Sobrevida , Estados Unidos/epidemiologia , United States Food and Drug Administration/organização & administração , United States Food and Drug Administration/tendências
11.
Ann Hematol ; 99(7): 1551-1560, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32504186

RESUMO

TP53 aberrations reportedly predict favorable responses to decitabine (DAC) in acute myeloid leukemia (AML). We evaluated clinical features and outcomes associated with chromosome 17p loss or TP53 gene mutations in older, unfit DAC-treated AML patients in a phase II trial. Of 178 patients, 25 had loss of 17p in metaphase cytogenetics; 24 of these had a complex (CK+) and 21 a monosomal karyotype (MK+). In analyses in all patients and restricted to CK+ and MK+ patients, 17p loss tended to associate with higher rates of complete remission (CR), partial remission (PR), or antileukemic effect (ALE). Despite favorable response rates, there was no significant OS difference between patients with or without loss of 17p in the entire cohort or in the CK+ and MK+ cohort. TP53 mutations were identified in eight of 45 patients with material available. Five of the eight TP53-mutated patients had 17p loss. TP53-mutated patients had similar rates of CR/PR/ALE but shorter OS than those with TP53 wild type (P = 0.036). Moreover, patients with a subclone based on mutation data had shorter OS than those without (P = 0.05); only one patient with TP53-mutated AML had a subclone. In conclusion, 17p loss conferred a favorable impact on response rates, even among CK+ and MK+ patients that however could not be maintained. The effect of TP53 mutations appeared to be different; however, patient numbers were low. Future research needs to further dissect the impact of the various TP53 aberrations in HMA-based combination therapies. The limited duration of favorable responses to HMA treatment in adverse-risk genetics AML should prompt physicians to advance allografting for eligible patients in a timely fashion.


Assuntos
Deleção Cromossômica , Decitabina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Monossomia , Síndrome de Smith-Magenis , Proteína Supressora de Tumor p53/genética , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 17/genética , Evolução Clonal/efeitos dos fármacos , Evolução Clonal/genética , Análise Mutacional de DNA , Feminino , Alemanha/epidemiologia , Humanos , Cariótipo , Cariotipagem , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Monossomia/diagnóstico , Monossomia/genética , Mutação , Síndrome de Smith-Magenis/diagnóstico , Síndrome de Smith-Magenis/epidemiologia , Síndrome de Smith-Magenis/genética , Análise de Sobrevida
12.
Pediatr Blood Cancer ; 67(7): e28340, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32359129

RESUMO

BACKGROUND: The frequency of pathogenic/likely pathogenic (P/LP) germline mutations in cancer-related genes among children with cancer in highly consanguineous populations is not well studied. METHODS: Whole-exome sequencing of germline DNA was performed in 60 children with acute leukemia. We used the St. Jude Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE) data portal for the classification of germline variants by the St. Jude Medal Ceremony pipeline. RESULTS: Fifty-seven patients had acute lymphoblastic leukemia (ALL) and three patients had acute myeloid leukemia. Parental consanguinity was present in 27 (45%) patients. All patients were of Arab ancestry. Three patients (5%) had a history of cancer in their siblings. Five patients (8.3%) had P/LP germline mutations in cancer-related genes. Three patients with B-ALL had heterozygous pathogenic mutations in TP53, BRCA1, and BRCA2; one patient with B-ALL had homozygous pathogenic mutation in PMS2; and one patient with T-ALL had LP homozygous mutation in AK2 that was associated with reticular dysgenesis. Among patients who had history of parental consanguinity, three (11%) had P/LP germline mutations compared with two (8%) in the absence of parental consanguinity. Fourteen (23%) patients had gold medal variants in cancer-related genes, 13 were heterozygous, and one was homozygous. Silver medal variants were present in 35 (58%) patients; all were heterozygous except one homozygous. CONCLUSIONS: Children with acute leukemia in Saudi Arabia had low frequency of P/LP mutations in cancer-related genes despite the high rate of consanguinity. Larger studies using whole-genome sequencing are needed to further explore the heritability of childhood leukemia.


Assuntos
Biomarcadores Tumorais/genética , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Sequenciamento Completo do Exoma/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Leucemia Mieloide Aguda/epidemiologia , Masculino , Prognóstico , Arábia Saudita/epidemiologia
13.
Ann Hematol ; 99(6): 1351-1360, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32363416

RESUMO

Acute myeloid leukemia (AML) represents the most common indication for allogeneic hematopoietic cell transplantation (HCT). This study aimed to address the implementation status of allogeneic HCT for adults with AML in Japan and to provide a comprehensive overview of post-transplant outcomes. For this purpose, we analyzed data of 15,186 patients undergoing allogeneic HCT between 1992 and 2016 who were consecutively reported to the Japanese nationwide transplantation registry. The constant increase in the annual number of transplantations was clearly attributable to the growth of unrelated transplantation, and umbilical cord blood transplantation currently accounts for one-third of all allogeneic HCTs. The proportion of older patients has increased steadily since 2000, approximately, in parallel with the introduction of reduced-intensity conditioning. The probability of overall survival (OS) was estimated at 41% (95% confidence interval (CI), 40-42%) for the entire cohort, 56% (95% CI, 55-57%) for patients transplanted in complete remission (CR), and 22% (95% CI, 21-23%) for those transplanted in non-CR. Multivariate analysis identified age, sex, performance status, disease status, cytogenetic risk, donor type, graft source, sex mismatch between the donor and the recipient, and year of transplantation as factors significantly associated with OS. These findings represent the real-world data in Japan, showing the changes in transplantation practice and a detailed estimation of post-transplant outcomes.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/tendências , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão/epidemiologia , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos , Condicionamento Pré-Transplante/tendências , Transplante Homólogo/métodos , Transplante Homólogo/tendências , Adulto Jovem
14.
Anticancer Res ; 40(5): 2917-2924, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366443

RESUMO

BACKGROUND/AIM: Acute myeloid leukemia (AML) is a biologically heterogeneous disease that can be classified into de novo AML and secondary AML. Secondary AML can be further divided into therapy-related AML (t-AML) or AML evolving from antecedent hematological disorder (AHD-AML). This study evaluated the characteristics and prognosis of secondary AML in a homogeneous East Asian population who are often under-represented. PATIENTS AND METHODS: This was a retrospective, longitudinal cohort study of Korean AML patients over 18 years old treated between January 2000 and December 2013. A total of 437 de novo AML (80.3%), 41 t-AML (7.5%), and 66 AHD-AML (12.1%) were evaluated. RESULTS: First, we found that secondary AML constituted about 19.7% of all AML cases, and t-AML was more prevalent than AHD-AML. Second, we determined AHD-AML as a prognostic factor for inferior survival, independent of other risk factors (HR=2.137, 95%CI=1.534-2.977, p<0.001). The induction response rates correlated well with the overall survival. Furthermore, AHD-AML was associated with worst treatment outcomes and prognosis regardless of cytogenetic risk or age. Interestingly, t-AML was generally associated with better outcomes compared to AHD-AML despite the similarities in treatment schema. CONCLUSION: Secondary AML represents a broad spectrum of diseases and t-AML should be addressed separately from AHD-AML.


Assuntos
Leucemia Mieloide Aguda/epidemiologia , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Estudos de Coortes , Análise Citogenética , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
16.
Am J Hematol ; 95(7): 792-798, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32242967

RESUMO

Invasive fungal infections (IFI) are a significant source of morbidity and mortality for patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Given the heterogeneity of the population receiving hypomethylating agents (HMA), it is difficult for clinicians to accurately assess their patients' risk of infection. Literature on the incidence of IFI following HMA is limited to several studies of azacitidine. The primary objective of this retrospective study was to establish the incidence of IFI in HMA treated AML/MDS patients at a large U.S. comprehensive cancer center. Secondary objectives included comparing incidence of IFI among pre-specified subgroups to identify potential risk factors for IFI. Two hundred three patients with AML, intermediate to very high risk MDS or chronic myelomonocytic leukemia who received at least two cycles of HMA were included. The incidence of IFI, as defined by the European Organization for Research and Treatment of Cancer / Invasive Fungal Infections Cooperative Group criteria, was 9.6%, with 20 IFI diagnosed following HMA (three proven, four probable, 13 possible). Among the proven cases of IFI, molds included Scedosporium and Fusarium spp. Eleven patients who developed IFIs were neutropenic upon initiating HMA. The majority (17/20) of infections occurred during the first four cycles. Given this incidence, mold-active prophylaxis can be considered in patients who are neutropenic at the start of therapy.


Assuntos
Antineoplásicos/efeitos adversos , Fusariose , Fusarium , Infecções Fúngicas Invasivas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Scedosporium , Idoso , Antineoplásicos/administração & dosagem , Feminino , Fusariose/induzido quimicamente , Fusariose/epidemiologia , Fusariose/prevenção & controle , Humanos , Incidência , Infecções Fúngicas Invasivas/induzido quimicamente , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/prevenção & controle , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/epidemiologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/epidemiologia , Estudos Retrospectivos , Fatores de Risco
18.
Clin Lab ; 66(3)2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32162869

RESUMO

BACKGROUND: Acute myeloid leukemia is a heterogeneous group of diseases characterized by the uncontrolled proliferation of hematopoietic stem cells (HSCs) and progenitor cells with a reduced capacity to differentiate into mature cells. CXC chemokine receptor (CXCR4) and its ligand stromal derived factor-1 (SDF-1/CXCL12) are important players involved in cross-talk between leukemia cells and the bone marrow (BM) microenvironment. The aim to study the association between the immunohistochemical CXCR4 expression and the clinical outcome of AML in adult Egyptian patients. METHODS: Fifty-eight patients suffering from AML were recruited for this study, with an age range from 18 to 60 years and presenting from January 2013 to March 2017. All patients were subjected to complete blood count, BM aspiration, immunophenotyping, BM trephine biopsy, immunohistochemical staining with CXCR4 McAb and cytogenetics when feasible. RESULTS: CXCR4 was widely expressed (55.2%) among the studied patients. There was a significant relationship between CXCR4 and patients' outcomes. Fifteen (71.4%) patients who died were CXCR4 positive. The estimated mean time until death among CXCR4 negative cases was 37.6 ± 4.04 months which was longer than that of CXCR4 positive cases who had mean of 20.04 ± 4.9 months p = 0.016. The risk for death among CXCR4 positive cases was higher than CXCR4 negative cases with hazard ratio (HR) = 2.147 (p = 0.048). CONCLUSIONS: These results suggest that CXCR4 was expressed in a subset of AML patients and was associated with poor prognosis. CXCR4 expression appears to be an independent prognostic factor for survival in a heterogeneous group of AML patients.


Assuntos
Leucemia Mieloide Aguda , Receptores CXCR4 , Adolescente , Adulto , Medula Óssea/química , Quimiocina CXCL12/análise , Quimiocina CXCL12/metabolismo , Feminino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Receptores CXCR4/análise , Receptores CXCR4/metabolismo , Adulto Jovem
19.
Eur J Cancer ; 130: 1-11, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32163883

RESUMO

AIM: Evidence for an association of foetal growth with acute myeloid leukaemia (AML) is inconclusive. AML is a rare childhood cancer, relatively more frequent in girls, with distinct features in infancy. In the context of the Childhood Leukemia International Consortium (CLIC), we examined the hypothesis that the association may vary by age, sex and disease subtype using data from 22 studies and a total of 3564 AML cases. METHODS: Pooled estimates by age, sex and overall for harmonised foetal growth markers in association with AML were calculated using the International Fetal and Newborn Growth Consortium for the 21st Century Project for 17 studies contributing individual-level data; meta-analyses were, thereafter, conducted with estimates provided ad hoc by five more studies because of administrative constraints. Subanalyses by AML subtype were also performed. RESULTS: A nearly 50% increased risk was observed among large-for-gestational-age infant boys (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.03-2.14), reduced to 34% in boys aged <2 years (OR: 1.34, 95% CI: 1.05-1.71) and 25% in boys aged 0-14 years (OR: 1.25, 95% CI: 1.06-1.46). The association of large for gestational age became stronger in boys with M0/M1subtype (OR: 1.80, 95% CI: 1.15-2.83). Large birth length for gestational age was also positively associated with AML (OR: 1.38, 95% CI: 1.00-1.92) in boys. By contrast, there were null associations in girls, as well as with respect to associations of decelerated foetal growth markers. CONCLUSIONS: Accelerated foetal growth was associated with AML, especially in infant boys and those with minimally differentiated leukaemia. Further cytogenetic research would shed light into the underlying mechanisms.


Assuntos
Leucemia Mieloide Aguda/epidemiologia , Adolescente , Fatores Etários , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Desenvolvimento Fetal , Humanos , Lactente , Recém-Nascido , Masculino , Fatores Sexuais
20.
J Cancer Res Clin Oncol ; 146(4): 1011-1020, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31919567

RESUMO

PURPOSE: The impact of myeloid sarcoma (MS) on clinical outcome of pediatric acute myeloid leukemia (AML) patients remains controversial. Moreover, little is known about the role of stem cell transplantation (SCT) in such patients. METHODS: Clinical data of patients with AML under 18 years of age were retrieved from the TARGET dataset. We analyzed the prevalence, clinical profile, molecular characteristics, and prognosis of MS in these patients. RESULTS: Among 884 pediatric patients with AML, the frequency of MS was 12.3%. Pediatric AML with MS was associated with age under 1-year, abnormal cytogenetics, and KMT2A rearrangement. Moreover, MS was associated with a low complete remission rate, high induction death, poor 5-year EFS, and OS. KMT2A rearrangement had a negative impact on clinical outcome in AML patients with MS. In addition, SCT had no significant effect on the survival of AML patients with MS. Multivariate analysis revealed that MS was an unfavorable prognostic factor in pediatric AML in terms of EFS (Hazard ratio 1.670, P < 0.001) and OS (Hazard ratio 1.623, P = 0.004). CONCLUSIONS: The presence of MS at diagnosis of pediatric AML is associated with poor clinical outcomes, particularly when associated with KMT2A rearrangements. Moreover, pediatric patients with AML and MS may not benefit from SCT.


Assuntos
Leucemia Mieloide Aguda/diagnóstico , Sarcoma Mieloide/diagnóstico , Adolescente , Criança , Pré-Escolar , Feminino , Rearranjo Gênico , Histona-Lisina N-Metiltransferase/genética , Humanos , Lactente , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Masculino , Proteína de Leucina Linfoide-Mieloide/genética , Prognóstico , Sarcoma Mieloide/epidemiologia , Sarcoma Mieloide/genética , Sarcoma Mieloide/patologia
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