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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 25 ( 2019-09-01), p. 2217-2225
    Kurzfassung: To develop and validate prediction models for low and very low bone mineral density (BMD) on the basis of clinical and treatment characteristics that identify adult survivors of childhood cancer who require screening by dual-energy x-ray absorptiometry. PATIENTS AND METHODS White survivors of childhood cancer (n = 2,032; median attained age, 29.3 years [range, 18.1 to 40.9 years]) enrolled in the St Jude Lifetime Cohort (SJLIFE; development) and survivors treated at the Erasmus Medical Center (validation) in the Netherlands (n = 403; median age, 24.2 years [range, 18.0 to 40.9 years] ) were evaluated with dual-energy x-ray absorptiometry to determine lumbar spine BMD and total-body BMD. Low and very low BMD were defined as lumbar spine BMD and/or total-body BMD z scores of −1 or lower or −2 or lower, respectively. Multivariable logistic regression was used to build prediction models; performance was assessed using receiver operating characteristic curves. Diagnostic values were calculated at different probabilities. RESULTS Low BMD was present in 51% and 45% of SJLIFE and Dutch participants, respectively, and very low BMD was present in 20% and 10%, respectively. The model for low BMD included male sex (odds ratio [OR], 3.07), height (OR, 0.95), weight (OR, 0.98), attained age (OR, 0.97), current smoking status (OR, 1.48), and cranial irradiation (OR, 2.11). Areas under the curve were 0.72 (95% CI, 0.70 to 0.75) in the SJLIFE cohort and 0.69 (95% CI, 0.64 to 0.75) in the Dutch cohort. The sum of the sensitivity (69.0%) and specificity (64.0%) was maximal at the predicted probability of 50%. The model for very low BMD included male sex (OR, 3.28), height (OR, 0.95), weight (OR, 0.97), attained age (OR, 0.98), cranial irradiation (OR, 2.07), and abdominal irradiation (OR, 1.61), yielding areas under the curve of 0.76 (95% CI, 0.73 to 0.78; SJLIFE cohort) and 0.75 (95% CI, 0.67 to 0.83; Dutch co hort). CONCLUSION Validated prediction models for low and very low BMD, using easily measured patient and treatment characteristics, correctly identified BMD status in most white adult survivors through age 40 years.
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2019
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: Cancer Medicine, Wiley, Vol. 10, No. 13 ( 2021-07), p. 4177-4194
    Kurzfassung: Prevalent vitamin D deficiency (VDD) and low bone mineral density (BMD) have led to vitamin D supplementation for children with cancer, regardless vitamin D status. However, it remains unsettled whether this enhances bone strength. We sought to address this issue by carrying out a systematic review of the literature. Methods We conducted a literature search using PubMed, Embase, and Cochrane databases. Studies including children up to 5 years after cancer therapy were assessed for the association between 25‐hydroxyvitamin D (25OHD) levels and BMD Z ‐scores or fractures, and the effect of vitamin D supplementation on BMD or fractures. Evidence quality was assessed using the GRADE methodology. Results Nineteen studies (16 observational and 3 interventional, mainly involving children with hematologic malignancies) were included. One study which analyzed 25OHD as a threshold variable (≤10 ng/ml) found a significant association between 25OHD levels and BMD Z ‐scores, while 25OHD as a continuous variable was not significantly associated with BMD Z ‐scores in 14 observational studies. We found neither a significant association between lower 25OHD levels and fractures (2 studies), nor between vitamin D (and calcium) supplementation and BMD or fracture frequency (3 studies) (very low quality evidence). Conclusion There is a lack of evidence for an effect of vitamin D (and calcium) supplementation on BMD or fractures in children with cancer. Further research is needed; until then, we recommend dietary vitamin D/calcium intake in keeping with standard national guidelines, and periodic 25OHD monitoring to detect levels 〈 20 ng/ml. Vitamin D/calcium supplementation is recommended in children with low levels, to maintain levels ≥20 ng/ml year‐long.
    Materialart: Online-Ressource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2021
    ZDB Id: 2659751-2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 6026-6027
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
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    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2022
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4355-4355
    Kurzfassung: BACKGROUND Osteonecrosis and low bone mineral density (BMD) are serious osteogenic side effects of acute lymphoblastic leukemia (ALL) treatment. Bisphosphonates and recombinant human parathyroid hormone (rPTH) tend to be used to ameliorate osteonecrosis-related symptoms as well as to enhance bone mineral density in children with ALL and severe bone fragility. Only one preclinical study on the safety of bisphosphonates during ALL treatment is available, which raises concerns about their impact on leukemic drug sensitivity. Here, we assessed the influence of various bone-modifying agents (zoledronate, pamidronate and rPTH) on in vitro cytotoxicity of chemotherapeutic agents (vincristine (VCR), daunorubicin (DNR), dexamethasone (DEXA), 6-mercaptopurine (6-MP), PEG-asparaginase (PEG-ASP)) and prednisone (PRED) that are commonly used in ALL treatment. METHODS Potential cytotoxic effects of the bone-modifying agents on leukemia cell viability and on in vitro cytotoxic responses of chemotherapeutic agents were tested in various T-cell and B-cell leukemia cell lines using methyl-thiazol-tetrazolium (MTT) assays. Bone-modifying agents were added at concentrations up to a five-fold of their physiological peak plasma concentration. For each assay, 50th percentile of maximal inhibitory concentration was determined. To quantify the combined effects of the bone-modifying agents on chemotherapeutic agent-induced cytotoxicity, median (interquartile range) combination indexes (CI) were calculated. We considered a median CI of & lt; 0.8 as synergism and & gt; 1.2 as antagonism (based on the method of Chou). RESULTS Zoledronate, pamidronate or rPTH in combination with DNR, 6-MP and PEG-ASP showed median CI values between 0.8 and 1.2. Variable inconclusive results were obtained in combination with VCR. Only the combination of a five-fold peak plasma concentration of zoledronate or pamidronate with DEXA resulted in median CI values of 1.15 (range, 1.08-1.48), and 1.34 (range, 1.07-1.62), respectively. Additional experiments using DEXA as well as PRED in combination with one-, three- or five-fold physiological peak plasma concentrations of zoledronate or pamidronate revealed that median CI values stay within 0.8 and 1.2, except for DEXA exposed leukemia cells in combination with a five-fold physiological peak plasma concentration of pamidronate which repeatedly showed a median CI value above 1.2 (1.34, range 1.04-1.86). CONCLUSIONS Zoledronate, pamidronate or rPTH do not seem to influence drug sensitivity of DNR, 6-MP or PEG-ASP, even at a five-fold physiological peak plasma concentration. Nevertheless, our findings suggest a minimal effect of pamidronate on DEXA-induced leukemia cell death. This suggests that even though zoledronate or pamidronate do not seem to negatively influence DEXA- or PRED- induced toxicity in expected physiological concentrations (one- to three-fold physiological peak plasma concentrations), these bone-modifying agents may only be considered with caution in individual cases, and preferably in clinical trial settings before being applied on a large scale in children with ALL. Disclosures No relevant conflicts of interest to declare.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2021
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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