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Vitamin D, bone turnover markers and hCAP-18 in children with hemato-oncological diseases
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Description
Abstract [en]

Children with hemato-oncological diseases may have significant skeletal morbidities. Vitamin D is essential for the maintenance of skeletal health and may also be important for immunological functions and cancer outcomes. As vitamin D deficiency is a recognized problem in children worldwide, it is important to evaluate its prevalence among children and adolescents with hemato-oncological diseases in Sweden.

In this thesis, I investigated vitamin D status and its predictors, serum hCAP-18 (the pro-protein of the antimicrobial peptide LL-37 produced during neutrophil differentiation in the bone marrow), and bone turnover markers in children with hemato-oncological diseases at the time of diagnosis. 

Vitamin D deficiency was found in 30.9–46% of the children. Lower 25-hydroxyvitamin D level correlated with older age, seasons outside summer, a more recent calendar year of sampling, lack of vitamin D supplementation, and country of parental origin located between latitudes -45° and 45°. In preschool children with leukemia, a 25-hydroxyvitamin D level < 50 nmol/L was associated with inferior overall survival. 

There was no correlation between serum 25-hydroxyvitamin D and hCAP-18 neither in children with hemato-oncological diseases nor in healthy controls. Children with diseases that impair myelopoiesis presented low hCAP-18 levels, whereas those with non-hematological malignancies displayed serum hCAP-18 levels in the same range as that of healthy children.

Children diagnosed with leukemia had lower levels of bone formation and resorption markers than those of children with solid tumors or bone marrow failure. Adolescents with osteosarcoma displayed high bone alkaline phosphatase levels.

The identification of patients with suboptimal vitamin D status and compromised bone remodeling at cancer diagnosis may aid the development of supportive treatments that reduce the adverse effects of cancer and its treatment. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2023. , p. 61
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1938
Keywords [en]
vitamin D, pediatric cancer, leukemia, bone marrow failure, hCAP-18, bone turnover markers
National Category
Pediatrics
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-499601ISBN: 978-91-513-1785-4 (print)OAI: oai:DiVA.org:uu-499601DiVA, id: diva2:1748226
Public defence
2023-05-24, Rudbecksalen, Rudbeck Laboratory, Dag Hammarskjölds väg 20, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Funder
Swedish Childhood Cancer Foundation, TJ2020-0069, ST2013-0008Available from: 2023-05-02 Created: 2023-04-02 Last updated: 2023-05-02
List of papers
1. Vitamin D status in children with leukemia, its predictors, and association with outcome
Open this publication in new window or tab >>Vitamin D status in children with leukemia, its predictors, and association with outcome
2020 (English)In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 67, no 4, p. e28163-Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Children and adolescents with leukemia are potentially at high risk of vitamin D inadequacy, which may have clinical relevance for skeletal morbidity, infections, and cancer outcome. This study aimed to evaluate vitamin D status at the time of diagnosis to investigate its predictors and association with overall survival in children with leukemia. PROCEDURE: We included all 295 children and adolescents diagnosed with leukemia at our institution between 1990 and 2016 who had available serum sample from the time of diagnosis. We analyzed serum 25-hydroxyvitamin D and parathyroid hormone levels and correlated them with clinical data. RESULTS: The 25-hydroxyvitamin D level was deficient (< 25 nmol/L), insufficient (25-50 nmol/L), sufficient (50-75 nmol/L), and optimal (> 75 nmol/L) in 6.4%, 26.8%, 39.7%, and 27.1% of the children, respectively. Older age and a more recent time of sampling (calendar year) predicted lower 25-hydroxyvitamin D level. In preschool children (age </=6 years), lower 25-hydroxyvitamin D level was also associated with acute myeloid leukemia, and a 25-hydroxyvitamin D level < 50 nmol/L was associated with inferior overall survival. In school-aged children (age > 6 years), the 25-hydroxyvitamin D level showed significant seasonal variation. CONCLUSION: It remains unclear whether vitamin D supplementation in pediatric leukemia patients will improve outcome.

Place, publisher, year, edition, pages
Wiley, 2020
Keywords
adolescents, leukemia, overall survival, vitamin D, pediatric
National Category
Medical and Health Sciences
Research subject
Pediatrics
Identifiers
urn:nbn:se:uu:diva-407995 (URN)10.1002/pbc.28163 (DOI)000506527300001 ()
Available from: 2020-04-02 Created: 2020-04-02 Last updated: 2023-04-02Bibliographically approved
2. Prevalence of and factors influencing vitamin D deficiency in paediatric patients diagnosed with cancer at northern latitudes
Open this publication in new window or tab >>Prevalence of and factors influencing vitamin D deficiency in paediatric patients diagnosed with cancer at northern latitudes
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2021 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 110, no 7, p. 2252-2258Article in journal (Refereed) Published
Abstract [en]

Aim To investigate the prevalence of vitamin D deficiency among children with non-haematological malignancies and to explore possible causes of low vitamin D levels among these patients. Methods We performed a cross-sectional study of 458 children diagnosed with solid tumours, brain tumours, non-Hodgkin lymphoma or Hodgkin disease at the University Children's Hospital, Uppsala, Sweden. Serum 25-hydroxyvitamin D and parathyroid hormone levels were measured in samples taken at the time of cancer diagnosis and related to clinical data. Vitamin D deficiency was defined as a 25-hydroxyvitamin D level below 50 nmol/L. Results The prevalence rate of vitamin D deficiency among children with non-haematological malignancies was 41%. There was no association between sex or diagnosis and vitamin D status. Vitamin D deficiency was more common among school children than preschool children (51% vs. 24%). Older age, season outside summer, and a more recent calendar year were significant predictors of lower 25-hydroxyvitamin D. There was a significant, albeit weak, negative correlation between 25-hydroxyvitamin D and parathyroid hormone. Conclusion Vitamin D deficiency is common among children diagnosed with cancer, particularly among school-aged children diagnosed outside summer. The prevalence appears to be increasing, underlining the need for adequate replacement of vitamin D in these patients.

Place, publisher, year, edition, pages
John Wiley & SonsWILEY, 2021
Keywords
25&#8208, hydroxyvitamin D, solid tumour, brain tumour, non&#8208, Hodgkin lymphoma, Hodgkin disease
National Category
Pediatrics
Identifiers
urn:nbn:se:uu:diva-454526 (URN)10.1111/apa.15788 (DOI)000630050800001 ()33528842 (PubMedID)
Funder
Swedish Childhood Cancer Foundation, (PR2018-0101Swedish Childhood Cancer Foundation, (ST2013-0008Swedish Childhood Cancer Foundation, TJ2014-0007
Available from: 2021-09-28 Created: 2021-09-28 Last updated: 2024-01-15Bibliographically approved
3. The human cathelicidin hCAP-18 in serum of children with haemato-oncological diseases
Open this publication in new window or tab >>The human cathelicidin hCAP-18 in serum of children with haemato-oncological diseases
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2022 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 198, no 6, p. 1023-1031Article in journal (Refereed) Published
Abstract [en]

The human cathelicidin hCAP-18 (pro-LL-37) is the pro-protein of the antimicrobial peptide LL-37. hCAP-18 can be produced by many different cell types; bone marrow neutrophil precursors are the main source of hCAP-18 in the circulation. Neutrophil count is used as a marker for myelopoiesis but does not always reflect neutrophil production in the bone marrow, and thus additional markers are needed. In this study, we established the reference interval of serum hCAP-18 level in healthy children and compared serum hCAP-18 levels between different diagnostic groups of children with haemato-oncological diseases, at diagnosis. We found that children with diseases that impair myelopoiesis, such as acute leukaemia, aplastic anaemia, or myelodysplastic syndrome, presented with low hCAP-18 levels, whereas patients with non-haematological malignancies displayed serum hCAP-18 levels in the same range as healthy children. Children with chronic myeloid leukaemia presented with high circulating levels of hCAP-18, probably reflecting the high number of all differentiation stages of myeloid cells. We suggest that analysis of serum hCAP-18 provides additional information regarding myelopoiesis in children with haemato-oncological diseases, which may have future implications in assessment of myelopoiesis in clinical management.

Place, publisher, year, edition, pages
John Wiley & SonsWiley, 2022
Keywords
aplastic anaemia, cathelicidin, hCAP-18, leukaemia, myelopoiesis, paediatric cancer
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-492729 (URN)10.1111/bjh.18360 (DOI)000826602800001 ()35849644 (PubMedID)
Funder
Swedish Childhood Cancer Foundation, ST2013-0008Swedish Childhood Cancer Foundation, TJ2020-0069
Available from: 2023-01-10 Created: 2023-01-10 Last updated: 2024-01-15Bibliographically approved
4. Demographic and Disease-Related Factors Impact Bone Turnover and Vitamin D in Children with Hemato-Oncological Diseases
Open this publication in new window or tab >>Demographic and Disease-Related Factors Impact Bone Turnover and Vitamin D in Children with Hemato-Oncological Diseases
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(English)In: JBMR Plus, E-ISSN 2473-4039Article in journal (Other academic) Submitted
Keywords
vitamin D, bone turnover markers, leukemia, solid tumors, pediatric
National Category
Clinical Medicine Pediatrics
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-499600 (URN)
Funder
Swedish Childhood Cancer Foundation, TJ2020-0069, ST2013-0008
Available from: 2023-04-02 Created: 2023-04-02 Last updated: 2024-08-30

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