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  • 1
    Language: English
    In: Nature medicine, 2018-10, Vol.24 (10), p.1504-1506
    Description: We identified genetic mutations in CD19 and loss of heterozygosity at the time of CD19 relapse to chimeric antigen receptor (CAR) therapy. The mutations are present in the vast majority of resistant tumor cells and are predicted to lead to a truncated protein with a nonfunctional or absent transmembrane domain and consequently to a loss of surface antigen. This irreversible loss of CD19 advocates for an alternative targeting or combination CAR approach.
    Subject(s): Precursor Cell Lymphoblastic Leukemia-Lymphoma - immunology ; Immunotherapy, Adoptive ; Humans ; Antigens, CD19 - genetics ; Loss of Heterozygosity - genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Receptors, Chimeric Antigen - therapeutic use ; Drug Resistance, Neoplasm - genetics ; Receptors, Chimeric Antigen - immunology ; Receptors, Chimeric Antigen - genetics ; T-Lymphocytes - immunology ; Receptors, Antigen, T-Cell - genetics ; Mutation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology ; Antigens, CD19 - immunology ; Usage ; Care and treatment ; Gene mutations ; Genetic aspects ; Research ; Acute lymphocytic leukemia ; Gene therapy ; Index Medicus
    ISSN: 1078-8956
    E-ISSN: 1546-170X
    Source: Single Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: Drug design, development and therapy, 2018, Vol.12, p.3885-3898
    Description: Over the past decades, survival of patients with acute lymphoblastic leukemia (ALL) has dramatically improved, but the subgroup of patients with relapsed/refractory ALL still continues to have dismal prognosis. As an emerging therapeutic approach, chimeric antigen receptor-modified T-cells (CAR-T) represent one of the few practice-changing therapies for this subgroup of patients. Originally conceived and built in Philadelphia (University of Pennsylvania), CTL019 or tisagenlecleucel, the first CAR-T approved by the US Food and Drug Administration, showed impressive results in refractory/relapsed ALL since the publication on two pediatric patients in 2013. It is in this context that we provide a review of this product in terms of manufacturing, pharmacology, toxicity, and efficacy studies. Evaluation and management of toxicities, particularly cytokine release syndrome and neurotoxicity, is recognized as an essential part of the patient treatment with broader use of IL-6 receptor inhibitor. An under-assessed aspect, the quality of life of patients entering CAR-T cells treatment, will also be reviewed. By their unique nature, CAR-T cells such as tisagenlecleucel operate in a different way than typical drugs, but also provide unique hope for B-cell malignancies.
    Subject(s): Antigens ; Care and treatment ; Prognosis ; Acute lymphocytic leukemia ; Children ; T cells ; Health aspects ; Drug approval ; Index Medicus ; CTL019 ; Review ; tisagenlecleucel ; B-cell acute lymphoblastic leukemia ; Tisagenlecleucel
    ISSN: 1177-8881
    E-ISSN: 1177-8881
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 3
    Language: English
    In: Agronomy for sustainable development, 2017-08, Vol.37 (4), p.1-11
    Description: Maize is one of the world’s most important cereals, cultivated in a wide range of environments. Besides the importance of maize and the gains in yield from selection schemes, commercial breeding drastically reduced the number of cultivars of this crop. Current common sense states that hybrids, when compared to open-pollinated cultivars, are a better adaptation strategy to cope with the impacts of climate change. However, the performance and resilience of cultivars with different levels of improvement are still not explored in this context. Four cultivars—a commercial hybrid, one commercially improved open-pollinated, one improved open-pollinated derived from participatory breeding, and one from a farmer’s selection—were tested using the CERES-Maize crop model. Field experiments conducted in Brazil were used for calibration and evaluation. Synthetic scenarios of climate change resulted from the application of the incremental method on historical series of observations (30 years), with temperature increments ranging from +0.5 up to +3.0 °C and precipitation changes from −30 up to +30%. Planting dates consisted in nine dates (August 1–December 1, each 15 days). Results demonstrate that the model could mimic the phenology and yield of two improved open-pollinated cultivars (MPA01 and Fortuna) and the hybrid (AS1548). One open-pollinated cultivar could not be validated due to its high phenotypic variability. Yield response surfaces showed distinct impacts among cultivars, with improved open-pollinated cultivar MPA01 having a higher yield stability when compared to the hybrid. Early planting dates produced lower yields with higher risk of crop failure for all cultivars. Late planting dates produced higher yields with higher failure risk. Considering risk and yield, the best planting window for all cultivars and scenarios is between September and October. Our results demonstrate, for the first time, that improved open-pollinated cultivars are equivalent or more resilient than hybrids to yield changes under different scenarios of abiotic stresses.
    Subject(s): Local cultivars ; Zea mays ; Crop model ; Sustainable Development ; Corn ; Life Sciences ; Climate change ; DSSAT ; Model calibration ; Adaptation strategy ; Agriculture ; Yield ; Soil Science & Conservation ; Stresses ; Cereal crops ; Hybrids ; Cereals ; Stability ; Abiotic stress ; Crops ; Grain cultivation ; Rainfall ; Risk ; Response surfaces ; Resilience ; Precipitation ; Plant breeding ; Phenology ; Temperature effects ; Agricultural production ; Field tests ; Planting ; Crop yield ; Cultivars
    ISSN: 1774-0746
    E-ISSN: 1773-0155
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 4
    Language: English
    In: Leukemia, 2018-11, Vol.32 (11), p.2316-2325
    Description: The survival of pediatric patients with multiply relapsed and/or refractory (R/R) B-cell acute lymphoblastic leukemia has historically been very poor; however, data are limited in the current era. We conducted a retrospective study to determine the outcome of multiply R/R childhood B-ALL treated at 24 TACL institutions between 2005 and 2013. Patient information, treatment, and response were collected. Prognostic factors influencing the complete remission (CR) rate and event-free survival (EFS) were analyzed. The analytic set included 578 salvage treatment attempts among 325 patients. CR rates (mean ± SE) were 51 ± 4% for patients with bone marrow R/R B-ALL who underwent a second salvage attempt, 37 ± 6% for a third attempt, and 31 ± 6% for the fourth through eighth attempts combined. For patients achieving a CR after their second, third, and fourth through eighth attempts, the 2 year EFS was 41 ± 6%, 13 ± 7%, and 27 ± 13% respectively. Our results showed slight improvement when compared to previous studies. This is the largest and most recent study to date that evaluates the outcome of this patient population. Our data will provide detailed reference for the evaluation of new agents being developed for childhood B-ALL.
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 5
    Language: English
    In: Haematologica (Roma), 2007-10-01, Vol.92 (10), p.1431-1432
    Description: 1 Department of Internal Medicine, Medical School of Ribeirao Preto, Brazil; 2 Molecular Biology Laboratory, HEMOPE, Brazil; 3 Bone Marrow Transplantation Unit, Hospital Amaral Carvalho, Brazil 4 Hematology Service, University of Minas Gerais, Brazil; 5 Hematology and Bone Marrow Transplantation Unit, HCPA, Brazil; 6 Hematology Service, Santa Casa de São Paulo, Brazil; 7 Fundação Pio XII de Barretos, Brazil; 8 Hematology Service; HCPR, Brazil; 9 Clínica de Hematologia de Ribeirão Preto, Brazil; 10 Department of Hematology and Hemotherapy, UNIFESP, Brazil; 11 Oncominas, Brazil; 12 Hemocentro, State University of Campinas, Brazil; 13 International Outreach Program, St. Jude Children’s Research Hospital, Memphis, TN, USA Correspondence: Eduardo Magalhães Rego, Laboratório de Hematologia, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, São Paulo, 14048900, Brazil. Phone: international +55.16.36022888. Fax: international +55.16.36336695. E-mail: emrego{at}hcrp.fmrp.usp.br We report an increased incidence of high relapse risk features in 157 APL Brazilian patients. Out of 134 patients treated with ATRA and anthracyclines, only 91 (67.9%) achieved remission because 43 (32%) died during induction. The death rate during consolidation was 10.5%. Bleeding complications were the most frequent cause of failure (21.6%). Key words: acute promyelocytic leukemia, ATRA, developing countries, Brazil.
    Subject(s): Hematologic and hematopoietic diseases ; Chemotherapy ; Pharmacology. Drug treatments ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Biological and medical sciences ; Medical sciences ; Antineoplastic agents ; Leukemia, Promyelocytic, Acute - pathology ; Follow-Up Studies ; Humans ; Middle Aged ; Child, Preschool ; Male ; Treatment Outcome ; Leukemia, Promyelocytic, Acute - epidemiology ; Tretinoin - therapeutic use ; Adolescent ; Adult ; Female ; Aged ; Anthracyclines - therapeutic use ; Drug Therapy, Combination ; Child ; Brazil - epidemiology ; Leukemia, Promyelocytic, Acute - drug therapy ; Index Medicus
    ISSN: 0390-6078
    E-ISSN: 1592-8721
    Source: HighWire Press (Free Journals)
    Source: Directory of Open Access Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 6
    Language: English
    In: Pediatric blood & cancer, 2021-03, Vol.68 (3), p.e28727-n/a
    Description: Byline: Marie-Laure Colaiacovo, Nawar Dakhallah, Camille Jimenez-Cortes, Amalia Souza, Christophe Ah-Yan, Pascal Bernier, Henrique Bittencourt, Caroline Laverdiere, Jean-Marie Leclerc, Thai Hoa Tran
    Subject(s): COVID-19 ; Child, Preschool ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Acute Disease ; SARS-CoV-2 ; Humans ; Index Medicus
    ISSN: 1545-5009
    E-ISSN: 1545-5017
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 7
    Language: English
    In: Journal of plant interactions, 2016-01-01, Vol.11 (1), p.53-60
    Description: Allelopathy determines the dynamics of plant species in different environments. Understanding this biological phenomenon could help to develop applications in both natural and agricultural systems. This review summarizes the genetic and environmental characteristics that control the production and release of allelochemicals in agroecosystems. This study highlights the current understanding of the environmental changes caused by allelochemicals and summarizes the knowledge about the mechanisms of action of these compounds. Finally, it reviews novel applications of allelopathy in agricultural production systems, including the role of allelochemicals in consortia and their potential use in no-tillage cropping systems through cover crops or mulches.
    Subject(s): Plant secondary metabolites ; genetic characteristics ; allelochemicals ; allelopathic cover crops ; mechanisms of action
    ISSN: 1742-9145
    E-ISSN: 1742-9153
    Source: Taylor & Francis Open Access
    Source: Academic Search Ultimate
    Source: Directory of Open Access Journals
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  • 8
    Language: English
    In: Annals of hematology, 2016-06, Vol.95 (7), p.1169-1176
    Description: Febrile neutropenia (FN) requires immediate use of antibiotics (ATB), and procalcitonin (PCT) is proven to be useful in guiding antibiotic therapy in different settings. This study investigated the use of PCT as a guide for the duration of ATB in FN. A randomized controlled trial was carried out from January-December 2010. A total of 62 hematological adult patients with FN were randomized, in 1:1 ratio, into two groups: (1) PCT group: length of ATB guided by institutional protocol plus PCT dynamics, and (2) control group: duration of ATB in accordance with institutional protocol. There was no difference between groups regarding the use of ATB for the first episode of fever (HR 1.14, 95 % CI 0.66-1.95, p = 0.641), with equivalent median duration of ATB therapy (PCT group 9.0 days and control group 8.0 days, p = 0.67), and median number of days without ATB (0 days, IQR 0-2 days for both groups, p = 0.96). We observed no difference in clinical cure rate (p = 0.68), infection relapse (p = 1.0), superinfection (p = 0.85), length of hospitalization (p = 0.64), and mortality at 28 days (p = 0.39) and at 90 days (p = 0.72). Considering the cut-off of 0.5 ng/ml, PCT was correlated with bacteremia (sensitivity of 51.9 % and specificity of 76.5 %). In this randomized controlled trial, adding a PCT-guided protocol to the standard recommendations did not reduce the use of antibiotics in febrile neutropenia, although no apparent harm was caused. PCT proved to be a marker of bacteremia in this setting.
    Subject(s): Calcitonin - blood ; Anti-Bacterial Agents - blood ; Follow-Up Studies ; Humans ; Middle Aged ; Male ; Biomarkers - blood ; Anti-Bacterial Agents - therapeutic use ; Febrile Neutropenia - blood ; Febrile Neutropenia - drug therapy ; Length of Stay - trends ; Adult ; Female ; Disease Management ; Clinical trials ; Mortality ; Neutropenia ; Index Medicus
    ISSN: 0939-5555
    E-ISSN: 1432-0584
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 9
    Language: English
    In: Pediatric blood & cancer, 2019-09, Vol.66 (9), p.e27827-n/a
    Description: Chronic myeloid leukemia (CML) accounts for 2‐3% of leukemias in children under 15 and 9% in adolescents aged 15‐19. The diagnosis and management of CML in children, adolescents, and young adults have several differences compared to that in adults. This review outlines the diagnosis and management of the underlying disease as well as challenges that can occur when dealing with CML in this patient population.
    Subject(s): recommendations ; CML ; pediatric ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - diagnosis ; Humans ; Adolescent ; Child, Preschool ; Female ; Male ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - therapy ; Child ; Practice Guidelines as Topic ; Myelocytic leukemia ; Nonlymphoid leukemia ; Index Medicus ; Recommendations ; Pediatric
    ISSN: 1545-5009
    E-ISSN: 1545-5017
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 10
    Language: English
    In: Pediatric blood & cancer, 2020-07, Vol.67 (7), p.e28263-n/a
    Description: Introduction Indications for hematopoietic stem cell transplantation (HSCT) in pediatric acute myeloid leukemia (AML) are primarily dependent on risk stratification at diagnosis and relapse status. We sought to determine whether access to HSCT is influenced by regional and socioeconomic factors. Methods Children with newly diagnosed AML aged 〈 15 years between 2001 and 2015 were identified using the Cancer in Young People in Canada national population–based registry. Factors potentially associated with the receipt of HSCT were studied using univariate and multivariable logistic regression models. Results Overall, 568 children with newly diagnosed AML were included and 262 (46%) received HSCT. A greater proportion of patients, 103/157 (65.6%), underwent HSCT after first or subsequent relapse compared to 159/411 (38.7%) patients who underwent transplant before relapse. Among patients for whom HSCT would be considered before relapse, factors associated with higher odds of HSCT in a multivariable analysis were: poor versus good‐risk cytogenetics (Odds ratio [OR]: 30.0, 95% confidence interval [CI]: 7.7–117.0), diagnosis during 2012–2015 versus 2001–2006 (OR: 3.2, 95% CI: 1.6–6.3), diagnosis in eastern Canada versus central Canada (OR: 3.7, 95% CI: 1.9–7.3), and age 10–14 years versus age 〈 1 year (OR: 5.4, 95% CI: 2.3–12.8). Among patients for whom HSCT would be considered after first relapse, higher odds of HSCT was associated with diagnosis at a HSCT center (OR: 2.1, 95% CI: 1.1–4.1). Conclusion Patients diagnosed at a HSCT performing center and patients from eastern Canada had higher odds of receiving HSCT. This may suggest preferential access to HSCT for certain patients.
    Subject(s): geographical ; access to care ; acute myeloid leukemia ; sociodemographic ; universal health care ; hematopoietic stem cell transplant ; Index Medicus
    ISSN: 1545-5009
    E-ISSN: 1545-5017
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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