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  1. Article ; Online: Doing less, accomplishing more for childhood acute lymphoblastic leukaemia (ALL).

    Yeoh, Allen E J / Oh, Bernice L-Z / Ariffin, Hany

    British journal of haematology

    2021  Volume 194, Issue 4, Page(s) 661–662

    MeSH term(s) Child ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology ; Risk Factors
    Language English
    Publishing date 2021-07-06
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.17556
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Curing the Curable: Managing Low-Risk Acute Lymphoblastic Leukemia in Resource Limited Countries.

    Oh, Bernice L Z / Lee, Shawn H R / Yeoh, Allen E J

    Journal of clinical medicine

    2021  Volume 10, Issue 20

    Abstract: Although childhood acute lymphoblastic leukemia (ALL) is curable, global disparities in treatment outcomes remain. To reduce these global disparities in low-middle income countries (LMIC), a paradigm shift is needed: start with curing low-risk ALL. Low- ... ...

    Abstract Although childhood acute lymphoblastic leukemia (ALL) is curable, global disparities in treatment outcomes remain. To reduce these global disparities in low-middle income countries (LMIC), a paradigm shift is needed: start with curing low-risk ALL. Low-risk ALL, which accounts for >50% of patients, can be cured with low-toxicity therapies already defined by collaborative studies. We reviewed the components of these low-toxicity regimens in recent clinical trials for low-risk ALL and suggest how they can be adopted in LMIC. In treating childhood ALL, the key is risk stratification, which can be resource stratified. NCI standard-risk criteria (age 1-10 years, WBC < 50,000/uL) is simple yet highly effective. Other favorable features such as
    Language English
    Publishing date 2021-10-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm10204728
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Genetic Alterations in Childhood Acute Lymphoblastic Leukemia: Interactions with Clinical Features and Treatment Response.

    Lee, Shawn H R / Li, Zhenhua / Tai, Si Ting / Oh, Bernice L Z / Yeoh, Allen E J

    Cancers

    2021  Volume 13, Issue 16

    Abstract: Acute lymphoblastic leukemia (ALL) is the most common cancer among children. This aggressive cancer comprises multiple molecular subtypes, each harboring a distinct constellation of somatic, and to a lesser extent, inherited genetic alterations. With ... ...

    Abstract Acute lymphoblastic leukemia (ALL) is the most common cancer among children. This aggressive cancer comprises multiple molecular subtypes, each harboring a distinct constellation of somatic, and to a lesser extent, inherited genetic alterations. With recent advances in genomic analyses such as next-generation sequencing techniques, we can now clearly identify >20 different genetic subtypes in ALL. Clinically, identifying these genetic subtypes will better refine risk stratification and determine the optimal intensity of therapy for each patient. Underpinning each genetic subtype are unique clinical and therapeutic characteristics, such as age and presenting white blood cell (WBC) count. More importantly, within each genetic subtype, there is much less variability in treatment response and survival outcomes compared with current risk factors such as National Cancer Institute (NCI) criteria. We review how this new taxonomy of genetic subtypes in childhood ALL interacts with clinical risk factors used widely, i.e., age, presenting WBC,
    Language English
    Publishing date 2021-08-12
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13164068
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  4. Article: Associations of T-Cell Receptor Repertoire Diversity with L-Asparaginase Allergy in Childhood Acute Lymphoblastic Leukemia.

    Lee, Shawn H R / Li, Zhenhua / Lim, Evelyn H Z / Chin, Winnie H N / Jiang, Nan / Chiew, Kean Hui / Chen, Zhiwei / Oh, Bernice L Z / Tan, Ah Moy / Ariffin, Hany / Yang, Jun J / Yeoh, Allen E J

    Cancers

    2023  Volume 15, Issue 6

    Abstract: Asparaginase is a critical component of therapy for childhood acute lymphoblastic leukemia (ALL), but it is commonly associated with allergy, which results in morbidity and poorer outcomes. The underlying basis of this allergy is undoubtedly immune- ... ...

    Abstract Asparaginase is a critical component of therapy for childhood acute lymphoblastic leukemia (ALL), but it is commonly associated with allergy, which results in morbidity and poorer outcomes. The underlying basis of this allergy is undoubtedly immune-mediated, but the exact components of T-cell immunity have yet to be characterized. We performed longitudinal TCR sequencing of 180 bone marrow samples from 67 children with B-ALL treated as part of the Ma-Spore-ALL-2010 trial, and we evaluated the associations of TCR profile with asparaginase hypersensitivity, with functional validation of asparaginase activity in a separate cohort of 113 children. We found that a more diverse and dynamically changing TCR repertoire was associated with increased risk of clinical hypersensitivity and decreased L-asp activity. Allergic patients had a higher proportion of infrequent clonotypes, as well as a significantly lower degree of shared clonotypes amongst the cohort. Allergic patients also had significantly higher longitudinal variability of clonotypes across timepoints, where a higher dissimilarity between diagnosis and week 5 represented an 8.1-fold increased risk of an allergic event. After an allergy had occurred, there was shaping and convergence of the TCR repertoire towards a common antigen. Understanding the immunological basis of T-cell responses in allergy lays the groundwork for developing predictive biomarkers or strategies to mediate this common toxicity in childhood ALL.
    Language English
    Publishing date 2023-03-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15061829
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  5. Article ; Online: Predictors and Treatment Outcomes of Pediatric Osteosarcoma in Diverse Socioeconomic Backgrounds in Southeast Asia: A Retrospective Multicenter Study.

    Monsereenusorn, Chalinee / Alcasabas, Ana Patricia / Loh, Amos Hong Pheng / Soh, Shui Yen / Leung, Kenneth Wong Pak / Dhamne, Chetan / Blair, Sally / Lam, Catherine / Rujkijyanont, Piya / Traivaree, Chanchai / Photia, Apichat / Veerapan, Puwadon / Puhaindran, Mark E / Oh, Bernice L Z / Wang, Edward / Rodriguez-Galindo, Carlos

    Asian Pacific journal of cancer prevention : APJCP

    2022  Volume 23, Issue 2, Page(s) 631–640

    Abstract: Background: Pediatric osteosarcoma outcomes among developed and developing countries have not been previously compared. Countries in Southeast Asia (SEA) have a wide variety of socioeconomic statuses. A multi-institutional retrospective study was ... ...

    Abstract Background: Pediatric osteosarcoma outcomes among developed and developing countries have not been previously compared. Countries in Southeast Asia (SEA) have a wide variety of socioeconomic statuses. A multi-institutional retrospective study was conducted to determine the prognostic factors and outcomes for pediatric osteosarcoma in SEA.
    Methods: Pediatric patients with osteosarcoma treated between 1998 and 2017 in 4 SEA pediatric oncology centers were studied. Countries were classified using the World Bank Atlas method. Kaplan-Meier method and Cox's Proportion Hazard Model were applied to estimate survival outcomes and identify prognostic factors.
    Results: In all, 149 patients with osteosarcoma with a mean age of 12.48±3.66 years were enrolled. The localized to metastatic disease ratio was 1.5:1. The 5-year overall survival (OS) and event-free survival (EFS) were 53.8% and 42%, respectively. Prognostic factors associated with outcomes were country, stage of disease, MTX-containing regimens, and surgery type (p-value <0.05). In patients with localized disease, EFS was superior with limb-salvage surgery (62%) than amputation or rotationplasty (40%) (p-value 0.009). MTX-containing chemotherapies provided higher OS (45.3%) and EFS (37.9%) than non-MTX regimens (12.3% and 10.7%, respectively) among metastatic patients (p-value 0.004 and 0.005, respectively). Metastatic disease was an independent prognostic factor for death but not relapse outcome.  Conclusion: The disease outcomes in SEA were acceptable compared to developed countries. The stage of disease was the only independent prognostic factor. MTX-containing regimens and limb-salvage surgery should be considered where possible.
    MeSH term(s) Adolescent ; Amputation/mortality ; Antineoplastic Agents/therapeutic use ; Asia, Southeastern ; Bone Neoplasms/mortality ; Bone Neoplasms/therapy ; Child ; Female ; Humans ; Limb Salvage/mortality ; Male ; Methotrexate/therapeutic use ; Neoplasm Staging/mortality ; Osteosarcoma/mortality ; Osteosarcoma/therapy ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Socioeconomic Factors ; Treatment Outcome
    Chemical Substances Antineoplastic Agents ; Methotrexate (YL5FZ2Y5U1)
    Language English
    Publishing date 2022-02-01
    Publishing country Thailand
    Document type Journal Article ; Multicenter Study
    ZDB-ID 2218955-5
    ISSN 2476-762X ; 1513-7368
    ISSN (online) 2476-762X
    ISSN 1513-7368
    DOI 10.31557/APJCP.2022.23.2.631
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Life-threatening infections during treatment for acute lymphoblastic leukemia on the Malaysia-Singapore 2003 and 2010 clinical trials: A risk prediction model.

    Oh, Bernice L Z / Fan, Lijia / Lee, Shawn H R / Foo, Koon Mian / Chiew, Kean Hui / Seeto, Zelia Z L / Chen, Zhi Wei / Neoh, Cheryl C C / Liew, Germaine S M / Eng, Jing Jia / Lam, Joyce C M / Quah, Thuan Chong / Tan, Ah Moy / Chan, Yiong Huak / Yeoh, Allen E J

    Asia-Pacific journal of clinical oncology

    2022  Volume 18, Issue 5, Page(s) e456–e468

    Abstract: Aim: Life-threatening infections significantly impact the care of children undergoing therapy for acute lymphoblastic leukemia (ALL) who are at risk of severe sepsis due to both host and treatment factors. Our aim was to develop a life-threatening ... ...

    Abstract Aim: Life-threatening infections significantly impact the care of children undergoing therapy for acute lymphoblastic leukemia (ALL) who are at risk of severe sepsis due to both host and treatment factors. Our aim was to develop a life-threatening infection risk prediction model that would allow remote rapid triage of patients to reduce time to first dose of antibiotics and sepsis-related mortality.
    Methods: A retrospective analysis of 2068 fever episodes during ALL therapy was used for model building and subsequent internal validation.
    Results: Three hundred and seventy-seven patients were treated for ALL in two institutions with comparable critical and supportive care resources. A total of 55 patients accounted for 71 admissions to the critical care unit for sepsis that led to eight septic deaths during a 16-year study period. A retrospective analysis of risk factors for sepsis enabled us to build a model focused on 13 variables that discriminated admissions requiring critical care well: area under the receiver operating characteristic curve of .82; 95% CI .76-.87, p<.001, and Brier score of .033. Significant univariate predictors included neutropenia, presence of symptoms of abdominal pain, diarrhea, fever during induction or steroid-based phases, and the lack of any localizing source of infection at time of presentation.
    Conclusion: We have developed a risk prediction model that can reliably identify ALL patients undergoing treatment who are at a higher risk of life-threatening sepsis. Clinical applicability can potentially be extended to low-middle income settings, and its utility should be further studied in real-world settings.
    MeSH term(s) Anti-Bacterial Agents/therapeutic use ; Child ; Clinical Trials as Topic ; Fever ; Humans ; Malaysia/epidemiology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Retrospective Studies ; Sepsis/chemically induced ; Sepsis/diagnosis ; Sepsis/drug therapy ; Singapore
    Chemical Substances Anti-Bacterial Agents
    Language English
    Publishing date 2022-02-08
    Publishing country Australia
    Document type Journal Article
    ZDB-ID 2187409-8
    ISSN 1743-7563 ; 1743-7555
    ISSN (online) 1743-7563
    ISSN 1743-7555
    DOI 10.1111/ajco.13756
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  7. Article ; Online: Successful toxicity reduction during delayed intensification in the non-high-risk arm of Malaysia-Singapore Acute Lymphoblastic Leukaemia 2010 study.

    Oh, Bernice L Z / Lee, Shawn H R / Foo, Koon M / Chiew, Kean H / Seeto, Zelia Z L / Chen, Zhi W / Neoh, Cheryl C C / Liew, Germaine S M / Eng, Jing J / Lam, Joyce C M / Chan, Yiong H / Quah, Thuan C / Tan, Ah M / Yeoh, Allen E J

    European journal of cancer (Oxford, England : 1990)

    2020  Volume 142, Page(s) 92–101

    Abstract: In non-high-risk (non-HR) patients, the Malaysia-Singapore Acute Lymphoblastic Leukaemia 2003 (MS2003) study achieved good outcomes. However, its delayed-intensification (DI) phase, comprising repeated blocks of protocol III (2003-PIII), was toxic and ... ...

    Abstract In non-high-risk (non-HR) patients, the Malaysia-Singapore Acute Lymphoblastic Leukaemia 2003 (MS2003) study achieved good outcomes. However, its delayed-intensification (DI) phase, comprising repeated blocks of protocol III (2003-PIII), was toxic and caused significant treatment delays. The successor MS2010 study attempted to lower DI toxicity by replacing myelosuppressive drugs (doxorubicin, cytarabine) with vincristine and asparaginase.
    Patients and methods: We analysed 1748 admissions for fever in 315 Singapore children with non-HR acute lymphoblastic leukaemia (ALL) (MS2003, n = 183; MS2010, n = 132), comprising 76% of the total cohort (n = 413), to study the impact of these changes.
    Results: The new 2010-PVa which has no doxorubicin, was associated with significantly fewer hospitalisations due to fever (0.08 versus 0.30 admissions per block [A/blk], p < 0.001), as than 2003-PIIIa. Similarly in 2010-PIIIb and PVb, where one block of cytarabine was replaced by two doses of vincristine, admissions for fever were also fewer (0.47 versus 0.74 A/blk, p < 0.001) than in 2003-PIIIb. However, the addition of single doses of vincristine and asparaginase in 2010-PIIIa, even with a mandatory seven-day rest, led to more hospitalisations (0.45 A/blk, p < 0.001), increased risk of bacteraemia (relative-risk (RR) = 7.66, p = 0.005) and critical-care admissions (RR = 4.31, p = 0.13). Despite this, overall treatment-related mortality decreased from 2.7% to 0.8%. Taken together, the reduced phase delays allowed earlier completion of the intensive phase of treatment (standard risk: 38.1 versus 49.4 weeks, p < 0.001; intermediate risk: 50.9 versus 58.8 weeks, p < 0.001), while maintaining excellent 10-year event-free survival of 95.4% and overall survival of 96.2%.
    Conclusions: In non-HR ALL, replacing doxorubicin/cytarabine with vincristine/asparaginase during some DI blocks is effective in reducing toxicity without compromising outcomes.
    Clinical trial information: NCT0289464.
    MeSH term(s) Child ; Child, Preschool ; Female ; History, 21st Century ; Humans ; Infant ; Malaysia ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Singapore
    Language English
    Publishing date 2020-11-24
    Publishing country England
    Document type Historical Article ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 82061-1
    ISSN 1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
    ISSN (online) 1879-0852
    ISSN 0277-5379 ; 0959-8049 ; 0964-1947
    DOI 10.1016/j.ejca.2020.10.010
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