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1.
Rinsho Ketsueki ; 62(8): 988-997, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497239

RESUMO

Leukemia is caused by uncontrolled proliferation of immature hematopoietic progenitors. MLL fusion proteins, generated by chromosomal translocations, activate a broad range of previously transcribed genes to achieve the same expression profile as that of the parent cell in the daughter cells, thereby promoting self-renewal. Normally, replication of the expression profile only occurs in the hematopoietic stem cells (HSCs). A transactivation system comprised of MLL and AF4/ENL/P-TEFb (AEP) complexes promotes it by reactivating CpG-rich promoters. In the normal hematopoietic development, this system is tightly regulated and progressively suppressed during the course of hematopoietic differentiation so that non-HSC hematopoietic cells would not self-renew. Genetic mutations such as fusions of MLL and AEP components generate a constitutively active form of the MLL transcriptional machinery, which aberrantly promotes self-renewal even in non-HSC hematopoietic cells. In this review, I depict a molecular mechanism of MLL fusion-mediated leukemogenesis from a standpoint that leukemogenesis is driven by aberrant self-renewal that is mediated by hyper-active transcriptional machinery, and introduce several molecularly targeted therapies in the making which specifically perturb this transactivation system.


Assuntos
Leucemia , Proteína de Leucina Linfoide-Mieloide , Carcinogênese , Células-Tronco Hematopoéticas , Humanos , Leucemia/genética , Leucemia/terapia , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas de Fusão Oncogênica/genética
2.
Hematology ; 26(1): 637-647, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34474663

RESUMO

OBJECTIVES: The objective of the current study was to investigate the relationship between changes in vital signs and intensive care unit (ICU) admission. Windsor Regional Hospital treats 15-20 new patients a year with acute leukemia. These patients are at increased risk of neutropenic fevers and admission to the ICU following induction chemotherapy. METHODS: Retrospective review examined the correlation between acute leukemia patient vitals and ICU admission. The analysis included 37 patients: 7 ICU versus 30 controls. Changes were compared to baseline over 24 hours prior to ICU admission or 5 days after the initiation of induction chemotherapy in the following vital signs: heart rate (HR), mean arterial pressure (MAP), temperature (T), respiratory rate (RR), and fraction of inspired oxygen (FiO2) required to maintain a stable oxygen saturation. RESULTS: RR and FiO2 demonstrated significant change over baseline leading up to ICU admission within the ICU group. T, HR and MAP did not demonstrate significant changes over time in either group. RR, FiO2 and HR were significantly higher in the ICU group at time zero compared with the control group. RR was recorded least frequently in the 24 hours leading up to ICU admission. DISCUSSION: Changes in RR and FiO2 predicted clinical deterioration requiring ICU admission in acute leukemia patients. This is consistent with the predominant reason for ICU admission which was respiratory failure. CONCLUSION: We present preliminary evidence to support enhanced monitoring of RR and FiO2 in acute leukemia patients following induction chemotherapy with early intervention if identified.


Assuntos
Unidades de Terapia Intensiva , Leucemia , Admissão do Paciente , Sinais Vitais , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Leucemia/metabolismo , Leucemia/fisiopatologia , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
Curr Oncol Rep ; 23(10): 114, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34342734

RESUMO

PURPOSE OF REVIEW: The spread of the novel coronavirus SARS-CoV-2 and its associated disease, coronavirus disease of 2019 (COVID-19), has significantly derailed cancer care. Patients with leukemia are more likely to have severe infection and increased rates of mortality. There is paucity of information on how to modify care of leukemia patients in view of the COVID-19 risks and imposed restrictions. We review the available literature on the impact of COVID-19 on different types of leukemia patients and suggest general as well as disease-specific recommendations on care based on available evidence. RECENT FINDINGS: The COVID-19 infection impacts leukemia subtypes in variable ways and the standard treatments for leukemia have similarly, varying effects on the course of COVID-19 infection. Useful treatment strategies include deferring treatment when possible, use of less intensive regimens, outpatient targeted oral agents requiring minimal monitoring, and prioritization of curative or life-prolonging strategies. Reducing health care encounters, rational transfusion standards, just resource allocation, and pre-emptive advance care planning will serve the interests of leukemia patients. Ad hoc modifications based on expert opinions and extrapolations of previous well-designed studies are the way forward to navigate the crisis. This should be supplanted with more rigorous prospective evidence.


Assuntos
COVID-19/epidemiologia , Leucemia/terapia , COVID-19/prevenção & controle , COVID-19/terapia , Humanos , Leucemia/classificação , Leucemia/diagnóstico , Leucemia/epidemiologia , Assistência ao Paciente , Fatores de Risco , SARS-CoV-2
4.
Nat Commun ; 12(1): 4844, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381053

RESUMO

Acute leukemia relapsing after chemotherapy plus allogeneic hematopoietic stem cell transplantation can be treated with donor-derived T cells, but this is hampered by the need for donor/recipient MHC-matching and often results in graft-versus-host disease, prompting the search for new donor-unrestricted strategies targeting malignant cells. Leukemia blasts express CD1c antigen-presenting molecules, which are identical in all individuals and expressed only by mature leukocytes, and are recognized by T cell clones specific for the CD1c-restricted leukemia-associated methyl-lysophosphatidic acid (mLPA) lipid antigen. Here, we show that human T cells engineered to express an mLPA-specific TCR, target diverse CD1c-expressing leukemia blasts in vitro and significantly delay the progression of three models of leukemia xenograft in NSG mice, an effect that is boosted by mLPA-cellular immunization. These results highlight a strategy to redirect T cells against leukemia via transfer of a lipid-specific TCR that could be used across MHC barriers with reduced risk of graft-versus-host disease.


Assuntos
Antígenos CD1/imunologia , Glicoproteínas/imunologia , Leucemia/imunologia , Lisofosfolipídeos/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/imunologia , Doadores de Tecidos , Animais , Apresentação do Antígeno , Antígenos CD1/metabolismo , Glicoproteínas/metabolismo , Humanos , Imunoterapia Adotiva , Leucemia/metabolismo , Leucemia/terapia , Ativação Linfocitária , Camundongos , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/imunologia , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Ann Palliat Med ; 10(7): 7872-7883, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34353075

RESUMO

BACKGROUND: meta-analysis was performed to study the therapeutic effect of hematopoietic stem cell transplantation combined with killer cells (important immune cells of the body) on leukemia, hoping to enhance the postoperative therapeutic efficiency. METHODS: literatures were searched with "Hematopoietic stem cell transplantation", "killer cell", "leukemia", "Cytokine induction", etc. as search terms using Boolean logic search. Review Manager was utilized for meta-analysis after literature screening. RESULTS: eleven literatures were included, most of which were of low-risk bias (medium-high quality). Through meta-analysis, statistical heterogeneity was found in non-recurring mortality (NRM) between control group and experimental group (Chi2 =15.69, I2=62%, P=0.02). The leukemia-free survival rate between two groups was not heterogeneous (Chi2 =13.16, I2=32%, P=0.16), without considerable difference between groups (Z=1.52, P=0.13). The incidence of graft-versus-host disease (GvHD) between the two groups was statistically heterogeneous (Chi2 =21.38, I2=67%, P=0.003). The incidence of graft-versus-host disease in experimental group was greatly inferior to controls (Z=3.87, P=0.0001). DISCUSSION: hematopoietic stem cell transplantation combined with killer cells can effectively reduce the incidence of GvHD after stem cell transplantation in patients. The prognosis of transplantation was good, and it had no obvious effect on the overall survival rate and recurrence rate.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia , Células-Tronco Hematopoéticas , Humanos , Incidência , Leucemia/terapia
6.
Int J Mol Sci ; 22(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34445701

RESUMO

Chimeric antigen receptor (CAR) T-cells (CAR T-cells) are a promising therapeutic approach in treating hematological malignancies. CAR T-cells represent engineered autologous T-cells, expressing a synthetic CAR, targeting tumor-associated antigens (TAAs) independent of major histocompatibility complex (MHC) presentation. The most common target is CD19 on B-cells, predominantly used for the treatment of lymphoma and acute lymphocytic leukemia (ALL), leading to approval of five different CAR T-cell therapies for clinical application. Despite encouraging clinical results, treatment of other hematological malignancies such as acute myeloid leukemia (AML) remains difficult. In this review, we focus especially on CAR T-cell application in different hematological malignancies as well as strategies for overcoming CAR T-cell dysfunction and increasing their efficacy.


Assuntos
Neoplasias Hematológicas/terapia , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/tendências , Antígenos de Neoplasias/imunologia , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Humanos , Imunoterapia/métodos , Leucemia/imunologia , Leucemia/terapia , Linfoma/imunologia , Linfoma/terapia , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia
7.
Bone Joint J ; 103-B(8): 1400-1404, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34334046

RESUMO

AIMS: The aim of this study was to determine whether there is an increased prevalence of scoliosis in patients who have suffered from a haematopoietic malignancy in childhood. METHODS: Patients with a history of lymphoma or leukaemia with a current age between 12 and 25 years were identified from the regional paediatric oncology database. The medical records and radiological findings were reviewed, and any spinal deformity identified. The treatment of the malignancy and the spinal deformity, if any, was noted. RESULTS: From a cohort of 346 patients, 19 (5.5%) had radiological evidence of scoliosis, defined as a Cobb angle of > 10°. A total of five patients (1.4% of the total cohort) had a Cobb angle of > 40°, all of whom had corrective surgery. No patient with scoliosis had other pathology as a possible cause of the scoliosis and all had been treated with high doses of steroids for leukaemia, either acute or chronic myeloid, or acute lymphoblastic. CONCLUSION: There is an increased prevalence of idiopathic-like scoliosis and larger curves (Cobb angle of > 40°) associated with childhood leukaemia, which has not been previously reported in the literature. Causative factors may relate to the underlying disease process and/or its treatment. Cite this article: Bone Joint J 2021;103-B(8):1400-1404.


Assuntos
Leucemia , Linfoma , Escoliose/epidemiologia , Adolescente , Adulto , Criança , Estudos de Coortes , Feminino , Humanos , Leucemia/terapia , Linfoma/terapia , Masculino , Prevalência , Adulto Jovem
8.
Int J Mol Sci ; 22(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34298959

RESUMO

Blood malignancies often arise from undifferentiated hematopoietic stem cells or partially differentiated stem-like cells. A tight balance of multipotency and differentiation, cell division, and quiescence underlying normal hematopoiesis requires a special program governed by the transcriptional machinery. Acquisition of drug resistance by tumor cells also involves reprogramming of their transcriptional landscape. Limiting tumor cell plasticity by disabling reprogramming of the gene transcription is a promising strategy for improvement of treatment outcomes. Herein, we review the molecular mechanisms of action of transcription-targeted drugs in hematological malignancies (largely in leukemia) with particular respect to the results of clinical trials.


Assuntos
Reprogramação Celular , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hematológicas , Leucemia , Transcrição Genética , Animais , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Leucemia/genética , Leucemia/metabolismo , Leucemia/patologia , Leucemia/terapia
10.
Nat Med ; 27(8): 1458-1470, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34140705

RESUMO

Gene therapy (GT) has rapidly attracted renewed interest as a treatment for otherwise incurable diseases, with several GT products already on the market and many more entering clinical testing for selected indications. Clonal tracking techniques based on vector integration enable monitoring of the fate of engineered cells in the blood of patients receiving GT and allow assessment of the safety and efficacy of these procedures. However, owing to the limited number of cells that can be tested and the impracticality of studying cells residing in peripheral organs without performing invasive biopsies, this approach provides only a partial snapshot of the clonal repertoire and dynamics of genetically modified cells and reduces the predictive power as a safety readout. In this study, we developed liquid biopsy integration site sequencing, or LiBIS-seq, a polymerase chain reaction technique optimized to quantitatively retrieve vector integration sites from cell-free DNA released into the bloodstream by dying cells residing in several tissues. This approach enabled longitudinal monitoring of in vivo liver-directed GT and clonal tracking in patients receiving hematopoietic stem cell GT, improving our understanding of the clonal composition and turnover of genetically modified cells in solid tissues and, in contrast to conventional analyses based only on circulating blood cells, enabling earlier detection of vector-marked clones that are aberrantly expanding in peripheral tissues.


Assuntos
Ácidos Nucleicos Livres/genética , Vetores Genéticos/genética , Ácidos Nucleicos Livres/efeitos adversos , Terapia Genética , Humanos , Leucemia/genética , Leucemia/terapia , Leucodistrofia Metacromática/genética , Leucodistrofia Metacromática/terapia , Linfoma/genética , Linfoma/terapia
12.
J Med Chem ; 64(14): 9577-9591, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34191515

RESUMO

Chimeric antigen receptor T cell therapy has demonstrated antileukemia efficacy. However, this therapeutic approach is hampered by severe cytokine release syndrome, which is a major impediment to its widespread application in the clinic. The safety of this approach can be improved by engineering a rapid and reversible "off" or "on" safety switch for CAR-T cells. Cutting-edge investigations combining the advantages of genetic engineering and chemical technology have led to the invention of small-molecule-based safety switches for CAR-T cells. Small molecules such as FITC, folate, rimiducid, rapamycin, proteolysis-targeting chimera (PROTAC) compounds, and dasatinib are being investigated to design such safety switches. Optimized CAR-T cells may have enhanced therapeutic efficiency with fewer adverse effects. Herein we summarize and classify current novel small-molecule-based safety switches for CAR-T cells that aim to provide pharmacological control over the activities and toxicities associated with CAR-T cell-based cancer immunotherapies.


Assuntos
Antineoplásicos/uso terapêutico , Imunoterapia Adotiva , Leucemia/terapia , Bibliotecas de Moléculas Pequenas/uso terapêutico , Humanos , Estrutura Molecular
13.
Front Immunol ; 12: 657329, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33986748

RESUMO

A recent approach of hematopoietic stem cell (HSC) transplantation from haploidentical donors "mobilized" with G-CSF is based on the selective depletion of αß T and B lymphocytes from the graft. Through this approach, the patient receives both HSC and mature donor-derived effector cells (including NK cells), which exert both anti-leukemia activity and protection against infections. We previously showed that donor HSC mobilization with G-CSF results in accumulation in the graft of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), capable of inhibiting in vitro the anti-leukemia activity of allogeneic NK cells. Here, we performed a detailed gene expression analysis on NK cells and PMN-MDSCs both derived from mobilized graft. Cytotoxicity assays and real time PCR arrays were performed in NK cells. Microarray technology followed by bioinformatics analysis was used for gene expression profiling in PMN-MDSCs. Results indicate that NK cells from the graft have a lower cytolytic activity as compared to those from non-mobilized samples. Further, mobilized PMN-MDSCs displayed a peculiar transcriptional profile distinguishing them from non-mobilized ones. Differential expression of pro-proliferative and immune-modulatory genes was detected in mobilized PMN-MDSCs. These data strengthen the concept that G-CSF-mobilized PMN-MDSCs present in the graft display unique molecular characteristics, in line with the strong inhibitory effect on donor NK cells.


Assuntos
Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Células Matadoras Naturais/metabolismo , Células Supressoras Mieloides/metabolismo , Neutrófilos/metabolismo , Transcriptoma , Sobrevivência Celular , Biologia Computacional/métodos , Citotoxicidade Imunológica , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica , Sobrevivência de Enxerto/genética , Sobrevivência de Enxerto/imunologia , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Células Matadoras Naturais/imunologia , Leucemia/terapia , Células Supressoras Mieloides/imunologia , Neutrófilos/imunologia , Transcriptoma/efeitos dos fármacos , Transplante Haploidêntico
14.
Front Immunol ; 12: 652105, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968052

RESUMO

Transplantation of allogeneic hematopoietic cells faces two barriers: failure of engraftment due to a host versus graft reaction, and the attack of donor cells against the patient, the graft versus host (GVH) reaction. This reaction may lead to GVH disease (GVHD), but in patients transplanted due to leukemia or other malignant disorders, this may also convey the benefit of a graft versus leukemia (GVL) effect. The interplay of transplant conditioning with donor and host cells and the environment in the patient is complex. The microbiome, particularly in the intestinal tract, profoundly affects these interactions, directly and via soluble mediators, which also reach other host organs. The microenvironment is further altered by the modifying effect of malignant cells on marrow niches, favoring the propagation of the malignant cells. The development of stable mixed donor/host chimerism has the potential of GVHD prevention without necessarily increasing the risk of relapse. There has been remarkable progress with novel conditioning regimens and selective T-cell manipulation aimed at securing engraftment while preventing GVHD without ablating the GVL effect. Interventions to alter the microenvironment and change the composition of the microbiome and its metabolic products may modify graft/host interactions, thereby further reducing GVHD, while enhancing the GVL effect. The result should be improved transplant outcome.


Assuntos
Quimerismo , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia/terapia , Recidiva Local de Neoplasia/prevenção & controle , Intervalo Livre de Doença , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/imunologia , Reação Enxerto-Hospedeiro/efeitos dos fármacos , Reação Enxerto-Hospedeiro/genética , Reação Enxerto-Hospedeiro/imunologia , Efeito Enxerto vs Leucemia/genética , Efeito Enxerto vs Leucemia/imunologia , Humanos , Leucemia/genética , Leucemia/imunologia , Leucemia/mortalidade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/imunologia , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/efeitos adversos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
15.
Nat Biomed Eng ; 5(5): 429-440, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34002062

RESUMO

Avoiding the immune rejection of transplanted T cells is central to the success of allogeneic cancer immunotherapies. One solution to protecting T-cell grafts from immune rejection involves the deletion of allogeneic factors and of factors that activate cytotoxic immune cells. Here we report the generation of hypoimmunogenic cancer-antigen-specific T cells derived from induced pluripotent stem cells (iPSCs) lacking ß2-microglobulin, the class-II major histocompatibility complex (MHC) transactivator and the natural killer (NK) cell-ligand poliovirus receptor CD155, and expressing single-chain MHC class-I antigen E. In mouse models of CD20-expressing leukaemia or lymphoma, differentiated T cells expressing a CD20 chimeric antigen receptor largely escaped recognition by NKG2A+ and DNAM-1+ NK cells and by CD8 and CD4 T cells in the allogeneic recipients while maintaining anti-tumour potency. Hypoimmunogenic iPSC-derived T cells may contribute to the creation of off-the-shelf T cell immunotherapies.


Assuntos
Células-Tronco Pluripotentes Induzidas/citologia , Leucemia/terapia , Linfoma/terapia , Receptores Virais/genética , Linfócitos T/transplante , Microglobulina beta-2/genética , Animais , Antígenos de Diferenciação de Linfócitos T/metabolismo , Diferenciação Celular , Linhagem Celular , Técnicas de Inativação de Genes , Engenharia Genética , Humanos , Células-Tronco Pluripotentes Induzidas/imunologia , Leucemia/imunologia , Linfoma/imunologia , Masculino , Camundongos , Subfamília C de Receptores Semelhantes a Lectina de Células NK/metabolismo , Linfócitos T/citologia , Linfócitos T/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Immunity ; 54(4): 608-610, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33852826

RESUMO

Neoantigens are prime targets for cancer immunotherapy, but their identification in low mutational burden malignancies remains challenging. In this issue of Immunity, Ehx et al. show that atypical transcripts, and particularly retained introns, expand the spectrum of leukemia immunotherapy targets.


Assuntos
Leucemia , Neoplasias , Antígenos de Neoplasias/genética , Humanos , Imunoterapia , Leucemia/genética , Leucemia/terapia , Mutação
17.
Jpn J Clin Oncol ; 51(7): 1100-1106, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33822984

RESUMO

BACKGROUND: The incidence and background factors of sarcopenia and obesity in long-term survivors of childhood leukemia/lymphoma were not clear in Japan. METHODS: Between August 2018 and September 2019, we recruited adults aged ≥18 years who had childhood leukemia/lymphoma. Blood sampling, body composition measurement by bioelectrical impedance analysis and grip strength test were performed. RESULTS: Among 81 adult survivors (34 men and 47 women) with a median age of 25.0 years, 9 (11%) had sarcopenia and 10 (12%) had obesity, of whom, 3 had metabolic syndrome. Sarcopenia was observed in 7 (21%) of 33 survivors with hematopoietic stem cell transplantation (HSCT) and 2 (4%) of 48 survivors without hematopoietic stem cell transplantation (P = 0.012). The incidence of obesity was significantly higher in the cranial radiotherapy (P = 0.021) and non-transplanted cases (P = 0.042). Univariate logistic regression analysis revealed that hematopoietic stem cell transplantation for sarcopenia (odds ratio, 6.19; 95% confidence interval, 1.2-32.0; P = 0.03) and cranial radiotherapy for obesity (odds ratio, 5.6; 95% confidence interval, 1.4-22.4; P = 0.015) were significantly associated. Hypertension was more prevalent among the obese survivors, and higher transaminase levels were found more in both the sarcopenia and obese survivors than in others. CONCLUSIONS: Young adult survivors of childhood leukemia/lymphoma could be at risk of developing sarcopenia after hematopoietic stem cell transplantation and obesity after cranial radiotherapy. Further studies are required to assess the body composition of long-term survivors to find detailed risk factors of sarcopenia and metabolic syndrome.


Assuntos
Leucemia/epidemiologia , Linfoma/epidemiologia , Obesidade/epidemiologia , Sarcopenia/epidemiologia , Adolescente , Adulto , Sobreviventes de Câncer , Irradiação Craniana , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia/terapia , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Obesidade/etiologia , Sarcopenia/etiologia , Adulto Jovem
18.
Lancet Oncol ; 22(6): e254-e269, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33811813

RESUMO

Paediatric patients with cancer and those undergoing allogeneic haematopoietic cell transplantation have an increased susceptibility to invasive fungal diseases. In addition to differences in underlying conditions and comorbidities relative to adults, invasive fungal diseases in infants, children, and adolescents are unique in terms of their epidemiology, the validity of current diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of phase 3 clinical trials to provide data to guide evidence-based interventions. To re-examine the state of knowledge and to further improve invasive fungal disease diagnosis, prevention, and management, the 8th European Conference on Infections in Leukaemia (ECIL-8) reconvened a Paediatric Group to review the literature and to formulate updated recommendations according to the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and European Confederation of Medical Mycology (ECMM) grading system, which are summarised in this Review.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia/terapia , Micoses/terapia , Antifúngicos/uso terapêutico , Congressos como Assunto , Guias como Assunto , Humanos , Leucemia/complicações , Leucemia/epidemiologia , Leucemia/microbiologia , Micoses/complicações , Micoses/epidemiologia , Micoses/microbiologia , Pediatria/tendências
19.
Lancet Oncol ; 22(6): e270-e280, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33811814

RESUMO

Paediatric patients with cancer and those undergoing haematopoietic cell transplantation are at high risk of bacterial infections. The 8th European Conference on Infections in Leukaemia (ECIL-8) convened a Paediatric Group to review the literature and to formulate recommendations for the use of antibiotics according to the European Society of Clinical Microbiology and Infectious Diseases grading system. The evaluation of antibacterial prophylaxis included mortality, bloodstream infection, febrile neutropenia, emergence of resistance, and adverse effects as endpoints. Initial antibacterial therapy and antibiotic de-escalation or discontinuation focused on patients with a clinically stable condition and without previous infection or colonisation by resistant bacteria, and on patients with a clinically unstable condition or with previous infection or colonisation by resistant bacteria. The final considerations and recommendations of the ECIL-8 Paediatric Group on antibacterial prophylaxis, initial therapy, and de-escalation strategies are summarised in this Policy Review.


Assuntos
Antibacterianos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia/terapia , Micoses/terapia , Congressos como Assunto , Guias como Assunto , Humanos , Leucemia/complicações , Leucemia/epidemiologia , Leucemia/microbiologia , Micoses/complicações , Micoses/epidemiologia , Micoses/microbiologia , Pediatria/tendências
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