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1.
Int J Mol Sci ; 22(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33803981

RESUMO

Systemic mastocytosis (SM) is a hematologic neoplasm with abnormal accumulation of mast cells in various organ systems such as the bone marrow, other visceral organs and skin. So far, only little is known about epigenetic changes contributing to the pathogenesis of SM. In the current article, we provide an overview of epigenetic changes that may occur and be relevant to mastocytosis, including mutations in genes involved in epigenetic processes, such as TET2, DNMT3A and ASXL1, and global and gene-specific methylation patterns in neoplastic cells. Moreover, we discuss methylation-specific pathways and other epigenetic events that may trigger disease progression in mast cell neoplasms. Finally, we discuss epigenetic targets and the effects of epigenetic drugs, such as demethylating agents and BET-targeting drugs, on growth and viability of neoplastic mast cells. The definitive impact of these targets and the efficacy of epigenetic therapies in advanced SM need to be explored in future preclinical studies and clinical trials.


Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , Proteínas de Ligação a DNA/genética , Neoplasias Hematológicas/genética , Mastocitose Sistêmica/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Epigênese Genética/genética , Neoplasias Hematológicas/patologia , Humanos , Mastócitos/patologia , Mastocitose Sistêmica/patologia , Mutação/genética
2.
Pediatr Blood Cancer ; 68(6): e29005, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33719167

RESUMO

Information regarding the novel coronavirus disease (COVID-19) in pediatric oncology is limited. We conducted a systematic review of the available published literature on children with cancer affected by COVID-19. The last date of the study search was October 20, 2020, and 33 studies comprising 226 children were included for the final analysis. Data were extracted in a predefined data collection form, and the variables were extracted and analyzed. Patients with hematological malignancies were more in number. Males and children on intensive treatment were more frequently affected. Fever was the commonest symptom. The disease was asymptomatic/mild in 48% and severe in 9.6%. Consolidation, peribronchial cuffing, and consolidation with ground glass opacities were the common imaging findings. Hydroxychloroquine was the most frequently used drug for COVID-19. About 10% of children required intensive care, and about 32% had oxygen requirements. The percentage of children who died due to COVID-19 was 4.9%. The severity, morbidity, and mortality of COVID-19 in pediatric oncology were more compared to the general pediatric population. This information can help in risk stratification for the management of COVID-19.


Assuntos
/complicações , Neoplasias/complicações , Antimaláricos/uso terapêutico , /terapia , Criança , Cuidados Críticos/métodos , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Hidroxicloroquina/uso terapêutico , Neoplasias/patologia , Neoplasias/terapia , /isolamento & purificação , Resultado do Tratamento
3.
Int J Mol Sci ; 22(5)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652638

RESUMO

Acute kidney injury in patients who suffer a malignancy is a common complication. Due to its high prevalence and effective treatment, one of the most frequent causes that both oncologists and nephrologists must be aware of is acute tubulointerstitial nephritis (ATIN). ATIN is an immunomediated condition and the hallmark of the disease, with the presence of a tubulointerstitial inflammatory infiltrate in the renal parenchyma. This infiltrate is composed mainly of T lymphocytes that can be accompanied by macrophages, neutrophils, or eosinophils among other cells. One of the major causes is drug-related ATIN, and some antineoplastic treatments have been related to this condition. Worthy of note are the novel immunotherapy treatments aimed at enhancing natural immunity in order to defeat cancer cells. In the context of the immunosuppression status affecting ATIN patients, some pathogen antigens can trigger the development of the disease. Finally, hematological malignancies can also manifest in the kidney leading to ATIN, even at the debut of the disease. In this review, we aim to comprehensively examine differential diagnosis of ATIN in the setting of a neoplastic patient.


Assuntos
Neoplasias Hematológicas , Imunoterapia , Rim , Nefrite Intersticial , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Rim/imunologia , Rim/patologia , Macrófagos/imunologia , Macrófagos/patologia , Nefrite Intersticial/etiologia , Nefrite Intersticial/imunologia , Nefrite Intersticial/patologia , Nefrite Intersticial/terapia , Infiltração de Neutrófilos , Neutrófilos/imunologia , Neutrófilos/patologia , Linfócitos T/imunologia , Linfócitos T/patologia
4.
Lancet Haematol ; 8(3): e205-e215, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33636142

RESUMO

BACKGROUND: Diagnosis and remission status at the time of allogeneic haematopoietic stem-cell transplantation (HSCT) are the principal determinants of overall survival following transplantation. We sought to develop a contemporary disease-risk stratification system (DRSS) that accounts for heterogeneous transplantation indications. METHODS: In this retrospective cohort study we included 55 histology and remission status combinations across haematological malignancies, including acute leukaemia, lymphoma, multiple myeloma, and myeloproliferative and myelodysplastic disorders. A total of 47 265 adult patients (aged ≥18 years) who received an allogeneic HSCT between Jan 1, 2012, and Dec 31, 2016, and were reported to the European Society for Blood and Marrow Transplantation registry were included. We divided EBMT patients into derivation (n=25 534), tuning (n=18 365), and geographical validation (n=3366) cohorts. Disease combinations were ranked in a multivariable Cox regression for overall survival in the derivation cohort, cutoff for risk groups were evaluated for the tuning cohort, and the selected system was tested on the geographical validation cohort. An independent single-centre US cohort of 660 patients transplanted between Jan 1, 2010, and Dec 31, 2015 was used to externally validate the results. FINDINGS: The DRSS model stratified patients in the derivation cohort (median follow-up was 2·1 years [IQR 1·0-3·2]) into five risk groups with increasing mortality risk: low risk (reference group), intermediate-1 (hazard ratio for overall survival 1·26 [95% CI 1·17-1·36], p<0·0001), intermediate-2 (1·53 [1·42-1·66], p<0·0001), high (2·03 [1·86-2·22], p<0·0001), and very high (2·87 [2·63-3·13], p<0·0001). DRSS levels were also associated with a stepwise increase in risk across the tuning and geographical validation cohort. In the external validation cohort (median follow-up was 5·7 years [IQR 4·5-7·1]), the DRSS scheme separated patients into 4 risk groups associated with increasing risk of mortality: intermediate-2 risk (hazard ratio [HR] 1·34 [95% CI 1·04-1·74], p=0·025), high risk (HR 2·03 [95% CI 1·39-2·95], p=0·00023) and very-high risk (HR 2·26 [95% CI 1·62-3·15], p<0·0001) patients compared with the low risk and intermediate-1 risk group (reference group). Across all cohorts, between 64% and 65% of patients were categorised as having intermediate-risk disease by a previous prognostic system (ie, the disease-risk index [DRI]). The DRSS reclassified these intermediate-risk DRI patients, with 855 (6%) low risk, 7111 (51%) intermediate-1 risk, 5700 (41%) intermediate-2 risk, and 375 (3%) high risk or very high risk of 14 041 patients in a subanalysis combining the tuning and internal geographic validation cohorts. The DRI projected 2-year overall survival was 62·1% (95% CI 61·2-62·9) for these 14 041 patients, while the DRSS reclassified them into finer prognostic groups with overall survival ranging from 45·7% (37·4-54·0; very high risk patients) to 73·1% (70·1-76·2; low risk patients). INTERPRETATION: The DRSS is a novel risk stratification tool including disease features related to histology, genetic profile, and treatment response. The model should serve as a benchmark for future studies. This system facilitates the interpretation and analysis of studies with heterogeneous cohorts, promoting trial-design with more inclusive populations. FUNDING: The Varda and Boaz Dotan Research Center for Hemato-Oncology Research, Tel Aviv University.


Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Adulto , Estudos de Coortes , Feminino , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Sociedades Médicas , Taxa de Sobrevida , Transplante Homólogo
5.
Blood Adv ; 5(3): 913-925, 2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33560402

RESUMO

Tyrosine kinase inhibitors (TKIs) are used to target dysregulated signaling pathways in virtually all hematologic malignancies. Many of the targeted signaling pathways are also essential in nonmalignant immune cells. The current coronavirus severe acute respiratory syndrome coronavirus 2 pandemic catalyzed clinical exploration of TKIs in the treatment of the various stages of COVID-19, which are characterized by distinct immune-related complications. Most of the reported effects of TKIs on immune regulation have been explored in vitro, with different class-specific drugs having nonoverlapping target affinities. Moreover, many of the reported in vivo effects are based on artificial animal models or on observations made in symptomatic patients with a hematologic malignancy who often already suffer from disturbed immune regulation. Based on in vitro and clinical observations, we attempt to decipher the impact of the main TKIs approved or in late-stage development for the treatment of hematological malignancies, including inhibitors of Bruton's tyrosine kinase, spleen tyrosine kinase, BCR-Abl, phosphatidylinositol 3-kinase/ mammalian target of rapamycin, JAK/STAT, and FMS-like tyrosine kinase 3, to provide a rationale for how such inhibitors could modify clinical courses of diseases, such as COVID-19.


Assuntos
Imunidade Adaptativa , Neoplasias Hematológicas/tratamento farmacológico , Imunidade Inata , Inibidores de Proteínas Quinases/uso terapêutico , Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Tirosina Quinase da Agamaglobulinemia/metabolismo , /imunologia , Citocinas/metabolismo , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Proteínas de Fusão bcr-abl/metabolismo , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/patologia , Humanos , /isolamento & purificação
7.
Support Care Cancer ; 29(1): 79-84, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32803727

RESUMO

BACKGROUND: Verruciform xanthoma (VX) is an uncommon benign epithelial lesion which mainly appears in inflamed oral epithelium. In this study, our aim was to present new cases of oral VX (OVX) in chronic graft-versus-host disease (cGVHD) and review the literature. METHODS: We conducted a retrospective chart review of cGVHD patients (2012-2019) to reveal cases of OVX. The demographics, medical background, clinical presentation, treatment provided, and follow-up were obtained. Additionally, Medline was searched using the terms "graft-versus-host disease," "verruciform xanthoma," and "oral." Of the articles, the above-mentioned demographic and clinical features were retrieved. RESULTS: The patient pool included 133 oral cGVHD patients. Three cGVHD patients (males, aged 15-49 years, post-hematologic malignancy) were diagnosed with OVX. All patients had oral mucosal lichenoid lesions, but not in close proximity to the VX lesion. Medline searches revealed 9 cases of OVX in cGVHD patients reported in the literature. Eleven of the 12 patients had oral mucosal lichenoid lesions. Four patients had multiple OVX lesions. All lesions were asymptomatic. Six patients had lesions in the masticatory mucosa (hard palate and gingiva) and 4 patients had lesions in the buccal mucosa. CONCLUSIONS: To the best of our knowledge, this is the largest published OVX in cGVHD series, including 12 patients. It appears that despite the higher prevalence in cGVHD patients relative to the general population, OVXs do not necessarily develop in sites with lichenoid lesions. It is advised that clinicians be familiar with the clinical and histological features in order to consider OVX in the differential diagnosis of oral lesions in cGVHD patients.


Assuntos
Doença Enxerto-Hospedeiro/patologia , Doenças da Boca/patologia , Mucosa Bucal/patologia , Úlceras Orais/patologia , Xantomatose/patologia , Adolescente , Adulto , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Neoplasias Hematológicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Boca/diagnóstico , Estudos Retrospectivos , Adulto Jovem
8.
Am J Clin Pathol ; 155(2): 160-178, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33367495

RESUMO

OBJECTIVES: To summarize cases submitted to the 2019 Society for Hematopathology/European Association for Haematopathology Workshop under the category of myeloid/lymphoid neoplasms with eosinophilia and PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2 rearrangements, focusing on recent updates and relevant practice findings. METHODS: The cases were summarized according to their respective gene rearrangement to illustrate the spectrum of clinical, laboratory, and histopathology manifestations and to explore the appropriate molecular genetic tests. RESULTS: Disease presentations were heterogeneous, including myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDSs), MDS/MPN, acute myeloid leukemia, acute B- or T-lymphoblastic lymphoma/acute lymphoblastic lymphoma (ALL/LBL), or mixed-lineage neoplasms. Frequent extramedullary involvement occurred. Eosinophilia was common but not invariably present. With the advancement of RNA sequencing, cryptic rearrangements were recognized in genes other than PDGFRA. Additional somatic mutations were more frequent in the FGFR1-rearranged cases. Cases with B-ALL presentations differed from Philadelphia-like B-ALL by the presence of an underlying MPN. Cases with FLT3 and ABL1 rearrangements could be potential candidates for future inclusion in this category. CONCLUSIONS: Accurate diagnosis and classification of this category of myeloid/lymphoid neoplasms has important therapeutic implications. With the large number of submitted cases, we expand our understanding of these rare neoplasms and improve our ability to diagnose these genetically defined disorders.


Assuntos
Eosinofilia , Neoplasias Hematológicas , Diagnóstico Diferencial , Eosinofilia/etiologia , Eosinofilia/patologia , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/patologia , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética
9.
Am J Clin Pathol ; 155(2): 179-210, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33367563

RESUMO

OBJECTIVES: To report the findings of the 2019 Society for Hematopathology/European Association for Haematopathology Workshop within the categories of reactive eosinophilia, hypereosinophilic syndrome (HES), germline disorders with eosinophilia (GDE), and myeloid and lymphoid neoplasms associated with eosinophilia (excluding entities covered by other studies in this series). METHODS: The workshop panel reviewed 109 cases, assigned consensus diagnosis, and created diagnosis-specific sessions. RESULTS: The most frequent diagnosis was reactive eosinophilia (35), followed by acute leukemia (24). Myeloproliferative neoplasms (MPNs) received 17 submissions, including chronic eosinophilic leukemia, not otherwise specified (CEL, NOS). Myelodysplastic syndrome (MDS), MDS/MPN, and therapy-related myeloid neoplasms received 11, while GDE and HES received 12 and 11 submissions, respectively. CONCLUSIONS: Hypereosinophilia and HES are defined by specific clinical and laboratory criteria. Eosinophilia is commonly reactive. An acute leukemic onset with eosinophilia may suggest core-binding factor acute myeloid leukemia, blast phase of chronic myeloid leukemia, BCR-ABL1-positive leukemia, or t(5;14) B-lymphoblastic leukemia. Eosinophilia is rare in MDS but common in MDS/MPN. CEL, NOS is a clinically aggressive MPN with eosinophilia as the dominant feature. Bone marrow morphology and cytogenetic and/or molecular clonality may distinguish CEL from HES. Molecular testing helps to better subclassify myeloid neoplasms with eosinophilia and to identify patients for targeted treatments.


Assuntos
Eosinofilia , Neoplasias Hematológicas , Síndrome Hipereosinofílica , Leucemia Linfoide , Diagnóstico Diferencial , Eosinofilia/diagnóstico , Eosinofilia/etiologia , Eosinofilia/patologia , Feminino , Proteínas de Fusão bcr-abl/metabolismo , Predisposição Genética para Doença , Células Germinativas/patologia , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/patologia , Técnicas Histológicas , Humanos , Síndrome Hipereosinofílica/diagnóstico , Síndrome Hipereosinofílica/patologia , Leucemia/diagnóstico , Leucemia/patologia , Leucemia Linfoide/diagnóstico , Leucemia Linfoide/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mieloide de Fase Acelerada/diagnóstico , Leucemia Mieloide de Fase Acelerada/patologia , Masculino , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/patologia , Patologia Molecular , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia
10.
Int J Mol Sci ; 22(1)2020 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-33375664

RESUMO

Hypericum is a widely present plant, and extracts of its leaves, flowers, and aerial elements have been employed for many years as therapeutic cures for depression, skin wounds, and respiratory and inflammatory disorders. Hypericum also displays an ample variety of other biological actions, such as hypotensive, analgesic, anti-infective, anti-oxidant, and spasmolytic abilities. However, recent investigations highlighted that this species could be advantageous for the cure of other pathological situations, such as trigeminal neuralgia, as well as in the treatment of cancer. This review focuses on the in vitro and in vivo antitumor effects of St. John's Wort (Hypericum perforatum), its derivatives, and other Hypericum species in hematologic malignancies. Hypericum induces apoptosis in both myeloid and lymphoid cells. Other Hypericum targets include matrix metalloproteinase-2, vascular endothelial growth factor, and matrix metalloproteinase-9, which are mediators of cell migration and angiogenesis. Hypericum also downregulates the expression of proteins that are involved in the resistance of leukemia cells to chemotherapeutic agents. Finally, Hypericum and its derivatives appear to have photodynamic effects and are candidates for applications in tumor photodynamic therapy. Although the in vitro studies appear promising, controlled in vivo studies are necessary before we can hypothesize the introduction of Hypericum and its derivatives into clinical practice for the treatment of hematologic malignancies.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Hypericum/química , Extratos Vegetais/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Interações Medicamentosas , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/etiologia , Neoplasias Hematológicas/patologia , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Linfócitos/patologia , Células Mieloides/efeitos dos fármacos , Células Mieloides/metabolismo , Células Mieloides/patologia , Extratos Vegetais/química , Relação Estrutura-Atividade
11.
Cancer ; 126(23): 5069-5076, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32910456

RESUMO

BACKGROUND: Patients with cancer are considered highly vulnerable to the recent coronavirus disease 2019 (COVID-19) pandemic. However, there are still few data on COVID-19 occurring in hematologic patients. METHODS: One hundred two patients with COVID-19 symptoms and a nasopharyngeal swab positive for severe acute respiratory syndrome coronavirus 2 seen at 2 hematologic departments located in Lombardy, Italy, during March 2020 were studied. Risk factors for acquiring COVID-19 were analyzed by comparisons of patients with COVID-19 and the standard hematologic population managed at the same institutions in 2019. Thirty-day survival was compared with the survival of matched uninfected control patients with similar hematologic disorders and nonhematologic patients affected by COVID-19. RESULTS: Male sex was significantly more prevalent in patients with COVID-19. The infection occurred across all different types of hematologic disease; however, the risk of acquiring a COVID-19 infection was lower for patients with chronic myeloproliferative neoplasms, including chronic myeloid leukemia, and higher for patients with immune-mediated anemia on immunosuppressive-related treatments. The 30-day mortality rate was 39.2%, which was higher than the rates for nonhematologic patients with COVID-19 (23.5%; P = .02) and uninfected hematologic controls (3%; P < .001). The severity of the respiratory syndrome at presentation and active hematologic treatment were independently associated with a worse prognosis. Neither diagnosis nor disease status affected the prognosis. The worst prognosis was demonstrated among patients on active hematologic treatment and those with more severe respiratory syndrome at COVID-19 presentation. CONCLUSIONS: During the COVID-19 pandemic, patients should be advised to seek medical attention at the earliest signs of dyspnea and/or respiratory infection. Physicians should perform a risk-benefit analysis to determine the impact of temporarily deferring nonlifesaving treatments versus the risk of adverse outcomes associated with COVID-19. LAY SUMMARY: Coronavirus disease 2019 (COVID-19) infection occurs across all different types of hematologic disease; however, the risk of acquiring it is lower for patients with chronic myeloproliferative neoplasms, including chronic myeloid leukemia, and higher for patients with immune-mediated anemia on immunosuppressive treatment. The 30-day mortality rate is 39.2%, which is far higher than the rates for both uninfected hematologic controls (3%; P < .001) and nonhematologic patients with COVID-19 (23.5%; P = .02) despite matching for age, sex, comorbidities, and severity of disease. Variables independently associated with a worse prognosis are the severity of the respiratory syndrome at presentation and any type of active hematologic treatment. Neither diagnosis nor disease status influence the prognosis.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Pneumonia Viral/complicações , Idoso , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Feminino , Seguimentos , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/virologia , Humanos , Itália/epidemiologia , Masculino , Pandemias , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
12.
Anticancer Res ; 40(10): 5707-5713, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988896

RESUMO

BACKGROUND/AIM: Genetic variations of the non-coding RNA gene, ANRIL, have been associated with human diseases including cancer, type-2 diabetes, and atherosclerosis. In the present study, we investigated the potential associations of select ANRIL single nucleotide polymorphisms (SNPs) with overall survival and other clinical outcomes in adult patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT). PATIENTS AND METHODS: Genomic DNA was extracted from whole blood samples from 103 adult patients with hematologic malignancies who had received allo-HSCT followed by oral tacrolimus therapy. The genotypes of four select ANRIL SNPs, rs564398, rs1063192, rs2151280, and rs2157719 were determined using qRT-PCR-based genotyping assays. RESULTS: rs2151280 (C->T) in ANRIL was associated with worse overall survival in these patients (CT/CC vs. TT). Contrarily, rs2151280 and the other select ANRIL SNPs were not associated with death at Day-100 after transplantation, the incidence of graft-versus-host disease (GVHD), acute kidney injury (AKI), and neurotoxicity in the study cohort. CONCLUSION: rs2151280 represents a potential prognostic biomarker for overall survival in adult patients with hematologic malignancies after allo-HSCT.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Neoplasias Hematológicas/genética , RNA Longo não Codificante/genética , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/genética , Lesão Renal Aguda/patologia , Idoso , Feminino , Genótipo , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Intervalo Livre de Progressão , Tacrolimo/farmacocinética , Transplante Homólogo/efeitos adversos
15.
PLoS One ; 15(8): e0238124, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822433

RESUMO

BACKGROUND: Very elderly critically ill patients (ie, those older than 75 or 80 years) are an increasing population in intensive care units. However, patients with cancer have encompassed only a minority in epidemiological studies of very old critically-ill patients. We aimed to describe clinical characteristics and identify factors associated with hospital mortality in a cohort of patients aged 80 or older with cancer admitted to intensive care units (ICUs). METHODS: This was a retrospective cohort study in 94 ICUs in Brazil. We included patients aged 80 years or older with active cancer who had an unplanned admission. We performed a mixed effect logistic regression model to identify variables independently associated with hospital mortality. RESULTS: Of 4604 included patients, 1807 (39.2%) died in hospital. Solid metastatic (OR = 2.46; CI 95%, 2.01-3.00), hematological cancer (OR = 2.32; CI 95%, 1.75-3.09), moderate/severe performance status impairment (OR = 1.59; CI 95%, 1.33-1.90) and use of vasopressors (OR = 4.74; CI 95%, 3.88-5.79), mechanical ventilation (OR = 1.54; CI 95%, 1.25-1.89) and renal replacement (OR = 1.81; CI 95%, 1.29-2.55) therapy were independently associated with increased hospital mortality. Emergency surgical admissions were associated with lower mortality compared to medical admissions (OR = 0.71; CI 95%, 0.52-0.96). CONCLUSIONS: Hospital mortality rate in very elderly critically ill patients with cancer with unplanned ICU admissions are lower than expected a priori. Cancer characteristics, performance status impairment and acute organ dysfunctions are associated with increased mortality.


Assuntos
Estado Terminal/mortalidade , Mortalidade Hospitalar/tendências , Neoplasias/mortalidade , APACHE , Idoso de 80 Anos ou mais , Brasil , Estudos de Coortes , Feminino , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Hospitalização , Humanos , Unidades de Terapia Intensiva , Modelos Logísticos , Masculino , Neoplasias/patologia , Estudos Retrospectivos , Fatores de Risco
16.
PLoS One ; 15(8): e0236338, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785215

RESUMO

Dysregulation of BCL2 is a pathophysiology observed in haematological malignancies. For implementation of available treatment-options it is preferred to know the relative quantification of BCL2 mRNA with appropriate reference genes. For the choice of reference genes-(i) Reference Genes were selected by assessing variation of >60,000 genes from 4 RNA-seq datasets of haematological malignancies followed by filtering based on their GO biological process annotations and proximity of their chromosomal locations to known disease translocations. Selected genes were experimentally validated across various haematological malignancy samples followed by stability comparison using geNorm, NormFinder, BestKeeper and RefFinder. (ii) 43 commonly used Reference Genes were obtained from literature through extensive systematic review. Levels of BCL2 mRNA was assessed by qPCR normalized either by novel reference genes from this study or GAPDH, the most cited reference gene in literature and compared. The analysis showed PTCD2, PPP1R3B and FBXW9 to be the most unregulated genes across lymph-nodes, bone marrow and PBMC samples unlike the Reference Genes used in literature. BCL2 mRNA level shows a consistent higher expression in haematological malignancy patients when normalized by these novel Reference Genes as opposed to GAPDH, the most cited Reference Gene. These reference genes should also be applicable in qPCR platforms using Taqman probes and other model systems including cell lines and rodent models. Absence of sample from healthy-normal individual in diagnostic cases call for careful selection of Reference Genes for relative quantification of a biomarker by qPCR.BCL2 can be used as molecular diagnostics only if normalized with a set of reference genes with stable yet low levels of expression across different types of haematological malignancies.


Assuntos
Biomarcadores Tumorais/isolamento & purificação , Neoplasias Hematológicas/diagnóstico , Proteínas Proto-Oncogênicas c-bcl-2/isolamento & purificação , RNA Mensageiro/isolamento & purificação , RNA-Seq/normas , Animais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Medula Óssea/patologia , Linhagem Celular Tumoral , Conjuntos de Dados como Assunto , Modelos Animais de Doenças , Estudos de Viabilidade , Regulação Neoplásica da Expressão Gênica , Genes Essenciais , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/patologia , Humanos , Leucócitos Mononucleares , Proteínas Proto-Oncogênicas c-bcl-2/sangue , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/sangue , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real/normas , Padrões de Referência
17.
Lancet Haematol ; 7(9): e679-e689, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32791044

RESUMO

Although the incidence of HIV-associated lymphomas decreased after the introduction of effective combination antiretroviral therapy, they became the most common AIDS-related cancer in high-income countries. Moreover, as people living with HIV live longer, a wide range of non-AIDS-related cancer has emerged, including other haematological malignancies. Nonetheless, combination antiretroviral therapy has offered people with HIV the opportunity to receive the same therapies as those provided to the general population, and intensive curative therapies have become the standard. However, several population-based studies highlight a major health-care disparity between people with HIV and those without, with people who are HIV positive often excluded from using innovative therapies and participating in prospective trials. In addition, patients from low-income countries frequently receive inappropriate treatment. The hope is that with increased awareness of effective curative options these disparities will decrease, and people with HIV will be given the same therapeutic opportunities and enrolled in clinical trials alongside patients who are HIV negative.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Infecções por HIV/patologia , Neoplasias Hematológicas/tratamento farmacológico , Antirretrovirais/uso terapêutico , Saúde Global , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Humanos , Gradação de Tumores , Intervalo Livre de Progressão , Taxa de Sobrevida
18.
Value Health ; 23(7): 953-968, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32762998

RESUMO

OBJECTIVES: We performed a systematic review of health state utility values (HSUVs) obtained using the EQ-5D questionnaire for patients with hematologic malignancies. METHODS: The following databases were searched up to September 2018: MEDLINE, EMBASE, The Cochrane Library, and the EQ-5D publications database on the EuroQol website. Additional references were extracted from reviewed articles. Only studies presenting EQ-Index results were incorporated. In view of the heterogeneity across the included publications, we limited ourselves to a narrative synthesis of original HSUVs found. RESULTS: Fifty-nine studies (described in 63 articles) met the inclusion criteria. Data from 21 635 respondents provided 796 HSUV estimates for hematologic malignancy patients. EQ-Index scores ranged from -0.025 to 0.980. The most represented area was multiple myeloma (4 studies, 11 112 patients, and 249 HSUVs). In clinical areas such as chronic myeloid leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphoma, and mantle cell lymphoma, we described over 50 health utilities in each. In contrast, we identified only 13 HSUVs (based on 4 studies and the data of 166 patients) for Hodgkin lymphoma. Areas without EQ-5D-based health utilities comprised: polycythemia vera, primary myelofibrosis, essential thrombocythemia, mastocytosis, myeloid sarcoma, chronic myelomonocytic, eosinophilic leukemia, and neutrophilic leukemia. CONCLUSIONS: There is a wide range of HSUVs available for hematologic cancer patients with different indications. The review provides a catalog of utility values for use in cost-effectiveness models for hematologic malignancies.


Assuntos
Nível de Saúde , Neoplasias Hematológicas/psicologia , Qualidade de Vida , Análise Custo-Benefício , Neoplasias Hematológicas/economia , Neoplasias Hematológicas/patologia , Humanos , Modelos Econômicos , Inquéritos e Questionários
20.
Acta Cytol ; 64(6): 588-596, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32721953

RESUMO

INTRODUCTION: The nucleated-cell differential count on the bone marrow aspirate smears is required for the clinical diagnosis of hematological malignancy. Manual bone marrow differential count is time consuming and lacks consistency. In this study, a novel artificial intelligence (AI)-based system was developed to perform cell automatic classification of bone marrow cells and determine its potential clinical applications. MATERIALS AND METHODS: Bone marrow aspirate smears were collected from the Xinqiao Hospital of Army Medical University. First, an automated analysis system (Morphogo) scanned and generated whole digital images of bone marrow smears. Then, the nucleated marrow cells in the selected areas of the smears at a magnification of ×1,000 were analyzed by the software utilizing an AI-based platform. The cell classification results were further reviewed and confirmed independently by 2 experienced pathologists. The automatic cell classification performance of the system was evaluated using 3 categories: accuracy, sensitivity, and specificity. Correlation coefficients and linear regression equations between automatic cell classification by the AI-based system and concurrent manual differential count were calculated. RESULTS: In 230 cases, the classification accuracy was above 85.7% for hematopoietic lineage cells. Averages of sensitivity and specificity of the system were found to be 69.4 and 97.2%, respectively. The differential cell percentage of the automated count based on 200-500 cell counts was correlated with differential cell percentage provided by the pathologists for granulocytes, erythrocytes, and lymphocytes (r ≥ 0.762, p < 0.001). DISCUSSION/CONCLUSION: This pilot study confirmed that the Morphogo system is a reliable tool for automatic bone marrow cell differential count analysis and has potential for clinical applications. Current ongoing large-scale multicenter validation studies will provide more information to further confirm the clinical utility of the system.


Assuntos
Inteligência Artificial , Células da Medula Óssea/patologia , Medula Óssea/patologia , Neoplasias Hematológicas/patologia , Algoritmos , Humanos , Contagem de Leucócitos/métodos , Projetos Piloto , Sensibilidade e Especificidade
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