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.
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.
Summary 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.
Children and adolescents with leukemia are potentially at a high risk of developing vitamin D deficiency, due to limited physical activity and sunlight exposure, poor nutrition, chemotherapy, and its complications. The prevalence of vitamin D inadequacy in European pediatric cancer patients has been reported to be high. It is not known how many patients already have vitamin D deficiency at the time of diagnosis and whether vitamin D status at the time of diagnosis influences clinical outcome. We aimed to investigate vitamin D status in children with leukemia at the time of diagnosis and explore possible factors (age, type of leukemia, gender, year and season of sampling) contributing to a low level of 25-hydroxyvitamin D (25-OHD). Furthermore, we aimed to investigate if vitamin D status at the time of diagnosis influences overall survival. We carried out a cross-sectional study including all 295 children (169 boys, 57.3%) aged <18 years who were diagnosed with leukemia in our institution between 1991 and 2016 and had a stored serum sample available from the time of diagnosis. All samples had been stored at -80C. We analysed serum 25-OHD and PTH with reagents from the same batch in January 2018; 25-OHD levels <25 nmol/L were considered deficient, 25-50 nmol/L insufficient, 50-75 nmol/L sufficient, and ≥75nmol/L optimal. Clinical data (sex, age, diagnosis, date of the diagnosis, overall survival) were collected from the Swedish Childhood Cancer Registry. Altogether 295 children were included: 232 of them had acute lymphoblastic leukaemia (ALL), 52 acute myeloid leukaemia (AML), and 11 other types of leukemia (8 chronic myeloid leukaemia and 3 juvenile myelomonocytic leukaemia). Mean 25-OHD concentration was 60.7 nmol/L (SD 23.3). One third of the children (33.2%) had a subnormal 25-OHD level (6.4% had deficiency and 26.8% insufficiency), 39.7% were sufficient and 27.1% had an optimal level. There was a significant negative correlation between serum 25-OHD and PTH (p<0.001). Season affected serum 25-OHD: it was lowest in the spring (55.2 nmol/L, SD 21.7) and highest in the summer (68.4 nmol/L, SD 19.6). Multiple linear regression with unadjusted and adjusted analyses to explore the impact of age, diagnosis, gender, season, and time of sampling (calendar year) on 25-OHD level indicated that significant predictors of lower 25-OHD level were older age (p<0.001), sampling in the spring (p<0.001), sampling in more recent calendar year (p=0.001) and sampling in the winter (p=0.001). When exploring the impact of 25-OHD on survival, we used Cox proportional hazard regression. In the whole cohort only the diagnosis and the age at diagnosis were significant. However, when the younger patients (≤ 6 year of age) were analysed separately, 25-OHD level <50 nmol/L at the time of diagnosis was associated with inferior overall survival independently of other factors (HR 3.05, p=0.03) as compared with those with 25-OHD ≥50 nmol/L. This patient group included 163 patients with 16 events. Conclusion: Subnormal 25-OHD levels are common in pediatric patients with leukemia already at the time of diagnosis. In younger children with leukemia 25-OHD level <50 nmol/L is associated with inferior survival. Disclosures No relevant conflicts of interest to declare.
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