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  1. Article ; Online: Relapsed/Refractory T- Acute Lymphoblastic Leukemia - Current Options and Future Directions.

    Jeha, Sima

    Indian journal of pediatrics

    2023  Volume 91, Issue 2, Page(s) 168–175

    Abstract: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. The T-cell subtype (T-ALL) accounts for 10-15% of pediatric ALL cases and has been historically associated with outcomes inferior to those of B-cell ALL (B-ALL). The prognosis ... ...

    Abstract Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. The T-cell subtype (T-ALL) accounts for 10-15% of pediatric ALL cases and has been historically associated with outcomes inferior to those of B-cell ALL (B-ALL). The prognosis of T-ALL has significantly improved with contemporary intensive pediatric regimens. However, most children with relapsed T-ALL have dismal outcomes and fewer therapeutic salvage options than those available for B-ALL. After demonstrating efficacy in relapsed T-ALL, nelarabine is being increasingly incorporated into frontline T-ALL regimens. The development of genomic sequencing has led to the identification of new T-ALL subgroups and potential targeted therapeutic approaches which could improve patients' outcomes and reduce the toxicity associated with current therapy. Immunotherapy and cellular therapy regimens are also under early investigation in T-cell malignancies. This review outlines the clinical and biological characteristics of T-ALL and provides an overview of novel treatment options for refractory and relapsed T-ALL.
    MeSH term(s) Humans ; Child ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Prognosis ; Immunotherapy
    Language English
    Publishing date 2023-08-29
    Publishing country India
    Document type Journal Article ; Review
    ZDB-ID 218231-2
    ISSN 0973-7693 ; 0019-5456
    ISSN (online) 0973-7693
    ISSN 0019-5456
    DOI 10.1007/s12098-023-04745-z
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  2. Article: The burden and scope of childhood cancer in displaced patients in Jordan: The King Hussein Cancer Center and Foundation Experience.

    Rihani, Rawad / Jeha, Sima / Nababteh, Mayse / Rodriguez-Galindo, Carlos / Mansour, Asem / Sultan, Iyad

    Frontiers in oncology

    2023  Volume 13, Page(s) 1112788

    Abstract: Introduction: Jordan hosts one of the highest numbers of refugees per capita in the world, with the Syrian crisis leading to an influx of displaced persons to the already vulnerable population. However, limited resources and a lack of cancer-care ... ...

    Abstract Introduction: Jordan hosts one of the highest numbers of refugees per capita in the world, with the Syrian crisis leading to an influx of displaced persons to the already vulnerable population. However, limited resources and a lack of cancer-care strategies have made it difficult for refugees in Jordan to access quality cancer care. The King Hussein Cancer Center (KHCC) and Foundation (KHCF) have played a pivotal role in providing financial and medical support for displaced children with cancer, treating 968 non-Jordanian children with cancer between 2011-2022, with a median age of 6 years. Of these, 84% were fully funded by KHCF, and nationalities included Syrians (29%), Palestinians (26%), Iraqis (23%), and Yemenis (17%). Cancer diagnoses included solid tumors (44%), leukemia (23%), lymphoma (13%), bone sarcomas (9.5%), and retinoblastoma (9.1%). The median cost of treatment was JOD 18,000 (USD 25,352), with a total estimated cost of JOD 23.8 million (USD 33.5 million). More recently, in partnership with St. Jude Children's Research Hospital (SJCRH), two successive humanitarian funds (HF) were established to optimize cancer care for displaced children in Jordan.
    Results: Between February 2018 and September 2022, 51 children were fully treated on KHCC-SJCRH-HF, with a median age of 6 years and nationalities including Syrians (80%), Iraqis (6%), and Yemenis (8%). The most common cancer diagnoses were leukemia (41%), lymphoma (25%), solid tumors (24%), retinoblastoma (6%), and brain tumors (4%). Of these, 94% are alive and 51% are still receiving coverage. The median coverage for patients was JOD 21,808 (USD 30,715), and the total cost of treatment on KHCC/KHCF-SJCRH/American Lebanese Syrian-Associated Charities HF1 and HF2 was JOD 1.44 million (USD 1.97 million) and JOD 1.18 million (USD 1.67 million), respectively.
    Conclusion: This experience highlights the high burden of displaced children with cancer in Jordan, and the importance of local foundations like KHCC/KHCF and partnerships with international partners like SJCRH in providing lifesaving humanitarian initiatives and quality cancer care. Innovative cancer-care delivery models and sustainable financing are essential to ensure continuous coverage and access to cancer care for displaced persons in Jordan.
    Language English
    Publishing date 2023-03-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2023.1112788
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  3. Article ; Online: Cancer care for displaced children in Lebanon.

    Saab, Raya / Ghanem, Khaled / Jeha, Sima

    The Lancet. Oncology

    2021  Volume 22, Issue 12, Page(s) 1663–1664

    MeSH term(s) Child ; Child Health Services/standards ; Delivery of Health Care/standards ; Health Services Needs and Demand ; Humans ; Lebanon/epidemiology ; Neoplasms/diagnosis ; Neoplasms/epidemiology ; Neoplasms/therapy ; Refugees/statistics & numerical data
    Language English
    Publishing date 2021-12-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 2049730-1
    ISSN 1474-5488 ; 1470-2045
    ISSN (online) 1474-5488
    ISSN 1470-2045
    DOI 10.1016/S1470-2045(21)00631-8
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  4. Article: Post-PICU Cognitive and Psychological Outcomes in Children Receiving Treatments for Acute Lymphoblastic Leukemia.

    Canavera, Kristin / Ghafoor, Saad / Fan, Kimberly / Cheng, Cheng / Jeha, Sima / Pui, Ching-Hon / Elliott, Andrew / Morrison, R Ray / Jacola, Lisa M

    Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

    2023  Volume 24, Issue 12, Page(s) e584–e591

    Abstract: Objectives: To examine neurocognitive and psychological outcomes associated with post-PICU admissions in children treated for childhood acute lymphoblastic leukemia (ALL).: Design: Observational study from October 2007 to March 2017.: Setting: ... ...

    Abstract Objectives: To examine neurocognitive and psychological outcomes associated with post-PICU admissions in children treated for childhood acute lymphoblastic leukemia (ALL).
    Design: Observational study from October 2007 to March 2017.
    Setting: Pediatric onco-critical care unit.
    Patients: All patients in this study (n = 296; ages 3-21) were treated for ALL on the St. Jude Total Therapy 16 clinical trial (NCT00549848) from 2007 to 2017. Of these, 104 patients were admitted to the PICU during protocol-directed therapy. All patients completed protocol-directed neurocognitive monitoring prospectively, at the end of cancer-directed therapy. Data on PICU stays were abstracted retrospectively from the medical record.
    Interventions: None.
    Measurements and main results: Demographic and critical illness variables were abstracted from institutional databases and medical records. Neurocognitive and psychosocial outcomes were prospectively obtained at the end of treatment. Children who had a PICU admission experienced significantly lower functioning compared to normative samples in several areas of cognitive functioning (working memory, processing speed, executive functions, inattention, math achievement, fine motor dexterity, and speed), daily living skills, and internalizing problems (all ps < 0.05). Compared with those without PICU admissions, patients with PICU admissions had worse performance on a measure of sustained attention (p = 0.017). The frequency of patients at risk for problems with learning and memory was significantly higher in the PICU group compared with the non-PICU group (25% vs 12%, p = 0.006). Critical illness symptom severity was not associated with neurocognitive or psychological outcomes.
    Conclusions: Children with ALL, with or without a PICU admission, experienced lower cognitive and psychological outcomes following treatment. Future research is needed to continue identifying risk factors for post-intensive care syndrome (PICS-p) and post-PICU cognitive and psychological impairments in pediatric patients.
    MeSH term(s) Humans ; Child ; Critical Illness ; Retrospective Studies ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Cognition ; Intensive Care Units, Pediatric
    Language English
    Publishing date 2023-08-25
    Publishing country United States
    Document type Observational Study ; Journal Article
    ZDB-ID 2052349-X
    ISSN 1947-3893 ; 1529-7535
    ISSN (online) 1947-3893
    ISSN 1529-7535
    DOI 10.1097/PCC.0000000000003340
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  5. Article ; Online: Patient-Level Meta-analysis of Clofarabine in Acute Lymphoblastic Leukemia.

    Jeha, Sima / Goto, Hiroaki / Baruchel, André / Boëlle-Le Corfec, Emmanuelle / Geffriaud-Ricouard, Christine / Pieters, Rob / Shin, Hee Young

    Advances in therapy

    2023  Volume 40, Issue 12, Page(s) 5447–5463

    Abstract: Introduction: Clofarabine monotherapy at a dose of 52 mg/m: Methods: A systematic literature review was conducted, using the Dr.Evidence software platform, DOC Search, and Embase, to identify clinical trials with patients with R/R ALL who received ... ...

    Abstract Introduction: Clofarabine monotherapy at a dose of 52 mg/m
    Methods: A systematic literature review was conducted, using the Dr.Evidence software platform, DOC Search, and Embase, to identify clinical trials with patients with R/R ALL who received clofarabine monotherapy at 52 mg/m
    Results: A total of 754 patients in 12 clinical studies were analyzed including 682 patients with R/R ALL treated with clofarabine monotherapy at 52 mg/m
    Conclusion: In this meta-analysis, CR duration and median OS in pediatric patients with R/R ALL appeared to be slightly longer than in the phase II study. No new safety signals were identified. Results support the use of clofarabine monotherapy in its approved indication.
    MeSH term(s) Child ; Humans ; Acute Disease ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Clofarabine/therapeutic use ; Leukemia, Myeloid, Acute/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Recurrence ; Clinical Trials as Topic
    Chemical Substances Clofarabine (762RDY0Y2H)
    Language English
    Publishing date 2023-10-11
    Publishing country United States
    Document type Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Systematic Review
    ZDB-ID 632651-1
    ISSN 1865-8652 ; 0741-238X
    ISSN (online) 1865-8652
    ISSN 0741-238X
    DOI 10.1007/s12325-023-02696-7
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  6. Article ; Online: COVID-19 in Pediatric Patients With Acute Lymphoblastic Leukemia or Lymphoma.

    Hashmi, Saman K / Bodea, Jessica / Patni, Tushar / Angel, Savannah / Bhakta, Nickhill H / Jeha, Sima / Karol, Seth E / Ribeiro, Raul C / Rubnitz, Jeffrey E / Wolf, Joshua / Li, Yimei / Pui, Ching-Hon / Hijano, Diego R / Inaba, Hiroto

    JAMA network open

    2024  Volume 7, Issue 2, Page(s) e2355727

    Abstract: Importance: COVID-19 in pediatric patients with acute lymphoblastic leukemia or lymphoma (ALL/LLy) has not been described in detail and may affect chemotherapy administration and long-term outcomes.: Objective: To describe the clinical presentation ... ...

    Abstract Importance: COVID-19 in pediatric patients with acute lymphoblastic leukemia or lymphoma (ALL/LLy) has not been described in detail and may affect chemotherapy administration and long-term outcomes.
    Objective: To describe the clinical presentation of COVID-19 and chemotherapy modifications in pediatric patients with ALL/LLy.
    Design, setting, and participants: This is a retrospective case series of patients at St Jude Children's Research Hospital and its affiliate sites with newly diagnosed ALL/LLy who were treated on the Total XVII protocol (NCT03117751) between March 30, 2020, and June 20, 2022. Participants included patients aged 1 to 18 years who were receiving protocol chemotherapy. Acute symptoms and chemotherapy modifications were evaluated for 60 days after the COVID-19 diagnosis, and viral clearance, adverse events, and second SARS-CoV-2 infections were followed up during the 27-month study period.
    Exposures: SARS-CoV-2; all patients were screened at least weekly and at symptom onset and/or after known exposure to SARS-CoV-2.
    Main outcomes and measures: Description of the spectrum of COVID-19 illness and chemotherapy modifications.
    Results: Of 308 pediatric patients, 110 (36%) developed COVID-19 at a median age of 8.2 (IQR, 5.3-14.5) years. Sixty-eight patients (62%) were male. Most patients were in the continuation/maintenance phase of chemotherapy (101 [92%]). Severe disease was rare (7 [6%]) but was associated with older age, higher white blood cell counts at ALL/LLy diagnosis, lower absolute lymphocyte counts at COVID-19 diagnosis, abnormal chest imaging findings, and SARS-CoV-2 reinfection. Rare but serious thrombotic events included pulmonary embolism and cerebral venous sinus thrombosis (n = 1 for each). No multisystem inflammatory syndrome in children or death was seen. SARS-CoV-2 reinfection occurred in 11 patients (10%) and was associated with older age and with receiving standard or high-risk vs low-risk ALL/LLy therapy. Chemotherapy interruptions occurred in 96 patients (87%) and were longer for patients with severe disease, SARS-CoV-2 reinfection, and/or a COVID-19 diagnosis during the pre-Omicron variant period vs the post-Omicron period (after December 27, 2021).
    Conclusions and relevance: In this case series of COVID-19 in pediatric patients with ALL/LLy, severe COVID-19 was rare, but chemotherapy administration was affected in most patients. Long-term studies are needed to establish the outcomes of COVID-19 in this population.
    MeSH term(s) Humans ; Male ; Child ; Child, Preschool ; Adolescent ; Female ; COVID-19/complications ; COVID-19/epidemiology ; SARS-CoV-2 ; Retrospective Studies ; COVID-19 Testing ; Reinfection ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology ; Lymphoma/complications ; Lymphoma/epidemiology
    Language English
    Publishing date 2024-02-05
    Publishing country United States
    Document type Journal Article
    ISSN 2574-3805
    ISSN (online) 2574-3805
    DOI 10.1001/jamanetworkopen.2023.55727
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  7. Article: New therapeutic strategies in acute lymphoblastic leukemia.

    Jeha, Sima

    Seminars in hematology

    2009  Volume 46, Issue 1, Page(s) 76–88

    Abstract: While cure rates of over 80% are achieved in contemporary pediatric acute lymphoblastic leukemia (ALL) protocols, most adults with ALL succumb to their disease, and little progress has been made in the treatment of refractory and relapsed ALL. Moreover, ... ...

    Abstract While cure rates of over 80% are achieved in contemporary pediatric acute lymphoblastic leukemia (ALL) protocols, most adults with ALL succumb to their disease, and little progress has been made in the treatment of refractory and relapsed ALL. Moreover, the burden of therapy is high in a significant number of newly diagnosed patients, and in all those with relapse. Early response to therapy measured by minimal residual disease evaluation has proven the single most important prognostic factor and is increasingly used in risk stratification. However, as the benefit from intensification of frontline therapy becomes limiting, it becomes increasingly challenging to rescue patients who fail on contemporary risk-adapted protocols. New therapeutic strategies are needed, not only in salvage regimens but also in frontline protocols for patients who are at high risk of relapse. Current novel approaches include new formulations of existing chemotherapeutic agents, new antimetabolites and nucleoside analogs, monoclonal antibodies against leukemic-associated antigens, cellular immunotherapy, and molecular therapeutics. Some have already been adopted into standard regimens, while others remain in early stages of development. This review summarizes the current status of these novel therapies as they get integrated into ALL regimens.
    MeSH term(s) Adult ; Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents/therapeutic use ; Child ; Child, Preschool ; Clinical Trials, Phase I as Topic ; Clinical Trials, Phase II as Topic ; Drug Delivery Systems ; Folic Acid/metabolism ; Humans ; Nucleosides/therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Protein Kinase Inhibitors/therapeutic use
    Chemical Substances Antibodies, Monoclonal ; Antineoplastic Agents ; Nucleosides ; Protein Kinase Inhibitors ; Folic Acid (935E97BOY8)
    Language English
    Publishing date 2009-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 206923-4
    ISSN 1532-8686 ; 0037-1963
    ISSN (online) 1532-8686
    ISSN 0037-1963
    DOI 10.1053/j.seminhematol.2008.09.009
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  8. Article ; Online: Recent progress in the treatment of acute lymphoblastic leukemia: clofarabine.

    Jeha, Sima

    Hematology/oncology clinics of North America

    2009  Volume 23, Issue 5, Page(s) 1137–44, viii

    Abstract: Significant progress in the treatment of acute lymphoblastic leukemia (ALL) has been achieved through more effective use of established drugs in risk-adapted treatment regimens. As we are reaching the limits of optimizing current treatment strategies, ... ...

    Abstract Significant progress in the treatment of acute lymphoblastic leukemia (ALL) has been achieved through more effective use of established drugs in risk-adapted treatment regimens. As we are reaching the limits of optimizing current treatment strategies, new therapeutic targets are being identified, and novel formulation of older drugs are being explored. Clofarabine is a novel purine analog approved in 2005 for treating children in second or greater ALL relapse. Ongoing trials are studying the benefits of clofarabine combinations in less heavily pretreated patients, and the use of different dose schedules in a variety of hematologic malignancies.
    MeSH term(s) Adenine Nucleotides/therapeutic use ; Antineoplastic Agents/therapeutic use ; Arabinonucleosides/therapeutic use ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
    Chemical Substances Adenine Nucleotides ; Antineoplastic Agents ; Arabinonucleosides ; clofarabine (762RDY0Y2H)
    Language English
    Publishing date 2009-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 93115-9
    ISSN 1558-1977 ; 0889-8588
    ISSN (online) 1558-1977
    ISSN 0889-8588
    DOI 10.1016/j.hoc.2009.07.011
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  9. Article ; Online: Genomic analysis of venous thrombosis in children with acute lymphoblastic leukemia from diverse ancestries.

    Zheng, Yan / Yang, Wenjian / Estepp, Jeremie / Pei, Deqing / Cheng, Cheng / Takemoto, Clifford M / Inaba, Hiroto / Jeha, Sima / Pui, Ching-Hon / Relling, Mary V / Karol, Seth E

    Haematologica

    2024  Volume 109, Issue 1, Page(s) 53–59

    Abstract: Venous thrombosis is a common adverse effect of modern therapy for acute lymphoblastic leukemia (ALL). Prior studies to identify risks of thrombosis in pediatric ALL have been limited by genetic screens of pre-identified genetic variants or genome- wide ... ...

    Abstract Venous thrombosis is a common adverse effect of modern therapy for acute lymphoblastic leukemia (ALL). Prior studies to identify risks of thrombosis in pediatric ALL have been limited by genetic screens of pre-identified genetic variants or genome- wide association studies (GWAS) in ancestrally uniform populations. To address this, we performed a retrospective cohort evaluation of thrombosis risk in 1,005 children treated for newly diagnosed ALL. Genetic risk factors were comprehensively evaluated from genome-wide single nucleotide polymorphism (SNP) arrays and were evaluated using Cox regression adjusting for identified clinical risk factors and genetic ancestry. The cumulative incidence of thrombosis was 7.8%. In multivariate analysis, older age, T-lineage ALL, and non-O blood group were associated with increased thrombosis while non-low-risk treatment and higher presenting white blood cell count trended toward increased thrombosis. No SNP reached genome-wide significance. The SNP most strongly associated with thrombosis was rs2874964 near RFXAP (G risk allele; P=4x10-7; hazard ratio [HR] =2.8). In patients of non-European ancestry, rs55689276 near the α globin cluster (P=1.28x10-6; HR=27) was most strongly associated with thrombosis. Among GWAS catalogue SNP reported to be associated with thrombosis, rs2519093 (T risk allele, P=4.8x10-4; HR=2.1), an intronic variant in ABO, was most strongly associated with risk in this cohort. Classic thrombophilia risks were not associated with thrombosis. Our study confirms known clinical risk features associated with thrombosis risk in children with ALL. In this ancestrally diverse cohort, genetic risks linked to thrombosis risk aggregated in erythrocyte-related SNP, suggesting the critical role of this tissue in thrombosis risk.
    MeSH term(s) Child ; Humans ; Retrospective Studies ; Risk Factors ; Genome-Wide Association Study ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Venous Thrombosis/genetics ; Genomics ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease
    Language English
    Publishing date 2024-01-01
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2022.281582
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  10. Article ; Online: The Impact of Intensified CNS-Directed Therapy on Neurocognitive Outcomes in Survivors of Childhood Acute Lymphoblastic Leukemia Treated Without Cranial Irradiation.

    Jacola, Lisa M / Conklin, Heather M / Krull, Kevin R / Pei, Deqing / Cheng, Cheng / Reddick, Wilburn E / Pui, Ching-Hon / Jeha, Sima

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2022  Volume 40, Issue 36, Page(s) 4218–4227

    Abstract: Purpose: Findings from St Jude Total Therapy Study 16 (Total 16) showed early intensification of triple intrathecal therapy (ITT) improved CNS disease control for children with newly diagnosed acute lymphoblastic leukemia (ALL) at the greatest risk of ... ...

    Abstract Purpose: Findings from St Jude Total Therapy Study 16 (Total 16) showed early intensification of triple intrathecal therapy (ITT) improved CNS disease control for children with newly diagnosed acute lymphoblastic leukemia (ALL) at the greatest risk of CNS relapse. We examined the impact of this treatment on end-of-therapy neurocognitive outcomes.
    Methods: Between 2007 and 2017, 400 (83.5%) of 479 eligible patients treated with Total 16 risk-directed chemotherapy completed protocol-directed neurocognitive testing at the end of therapy. Intensified ITT was defined as ≥ 21 cumulative doses for patients with low-risk ALL (n = 70/194) and ≥ 27 doses for those with standard-to-high risk ALL (n = 81/206).
    Results: Compared with age-normative expectations, the overall group had significantly lower estimated intelligence quotient (
    Conclusion: Standard-to-high risk patients treated with intensified ITT are at moderately increased risk for neurocognitive problems. The findings suggest a threshold effect for ITT exposure, which can inform the design of future clinical trials and approaches to neurocognitive monitoring and intervention.
    MeSH term(s) Child ; Female ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Cranial Irradiation/adverse effects ; Executive Function ; Memory, Short-Term ; Survivors
    Language English
    Publishing date 2022-11-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.22.00263
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