Background Low levels of the enzyme ADAMTS13 and elevated inflammatory markers such as interleukin-6 (IL-6) are associated with worse outcomes in patients with acute myeloid leukaemia (AML). IL-6 produced by leukaemia cells suppresses ADAMTS13 activity and impairs hematopoietic differentiation. Vitamin D, which has known for its immunomodulatory effects, may reduce IL-6 levels. This study investigated the impact of vitamin D supplementation on IL-6 and ADAMTS13 levels in patients newly diagnosed with AML. Patients and method A total of 38 newly diagnosed AML patients and 14 healthy individuals were included. IL-6 and ADAMTS13 levels were measured in both groups at baseline. Among AML patients, 34 were found to have vitamin D deficiency. Seventeen of these patients received oral vitamin D supplementation for 28 days in addition to their standard chemotherapy. Serum levels of IL-6, ADAMTS13 and vitamin D were measured on the 1st and 28th days of chemotherapy. Statistical analyses included Mann–Whitney U test, Wilcoxon signed-rank test, and Spearman correlation. Results AML patients had significantly higher IL-6 (7.19 vs. 1.15 pg/mL; p = 0.00001) and lower ADAMTS13 (684 vs. 1205 ng/mL; p = 0.001) compared to controls. ADAMTS13 significantly increased by Day 28 (p = 0.0001), while IL-6 showed no overall change. However, among vitamin D-deficient patients receiving supplementation, IL-6 levels decreased significantly by Day 28 (p = 0.049). A negative correlation was found between vitamin D and IL-6 on Day 28 (r = –0.485; p = 0.035). No significant effect of vitamin D status was observed on ADAMTS13 levels. Conclusion Vitamin D supplementation was associated with a reduction in IL-6 levels, but did not influence ADAMTS13 levels in patients with AML. These findings support the potential role of vitamin D as an adjunct anti-inflammatory agent during induction chemotherapy. Further studies with larger samples and longer follow-up are recommended to clarify its therapeutic relevance. Trial registration number NCT05149339 in <a href="http://www.clinicaltrial.gov">www.clinicaltrial.gov</a> registered on 25/11/2021 'retrospectively registered’ with URL; <a href="https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000BKX8&selectaction=Edit&uid=U0005ZGQ&ts=98&cx=avh64j">https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000BKX8&selectaction=Edit&uid=U0005ZGQ&ts=98&cx=avh64j</a>.

Effect of vitamin D status on a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) and interleukin 6 in patients with acute myeloid leukaemia

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2025年7月16日

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Dina Ashraf Abdelhady,
Mervat Mostafa Mohamed Azab,
Ahmed A. Alnagar,
Nora Said

摘要

Background

Low levels of the enzyme ADAMTS13 and elevated inflammatory markers such as interleukin-6 (IL-6) are associated with worse outcomes in patients with acute myeloid leukaemia (AML). IL-6 produced by leukaemia cells suppresses ADAMTS13 activity and impairs hematopoietic differentiation. Vitamin D, which has known for its immunomodulatory effects, may reduce IL-6 levels. This study investigated the impact of vitamin D supplementation on IL-6 and ADAMTS13 levels in patients newly diagnosed with AML.

Patients and method

A total of 38 newly diagnosed AML patients and 14 healthy individuals were included. IL-6 and ADAMTS13 levels were measured in both groups at baseline. Among AML patients, 34 were found to have vitamin D deficiency. Seventeen of these patients received oral vitamin D supplementation for 28 days in addition to their standard chemotherapy. Serum levels of IL-6, ADAMTS13 and vitamin D were measured on the 1st and 28th days of chemotherapy. Statistical analyses included Mann–Whitney U test, Wilcoxon signed-rank test, and Spearman correlation.

Results

AML patients had significantly higher IL-6 (7.19 vs. 1.15 pg/mL; p = 0.00001) and lower ADAMTS13 (684 vs. 1205 ng/mL; p = 0.001) compared to controls. ADAMTS13 significantly increased by Day 28 (p = 0.0001), while IL-6 showed no overall change. However, among vitamin D-deficient patients receiving supplementation, IL-6 levels decreased significantly by Day 28 (p = 0.049). A negative correlation was found between vitamin D and IL-6 on Day 28 (r = –0.485; p = 0.035). No significant effect of vitamin D status was observed on ADAMTS13 levels.

Conclusion

Vitamin D supplementation was associated with a reduction in IL-6 levels, but did not influence ADAMTS13 levels in patients with AML. These findings support the potential role of vitamin D as an adjunct anti-inflammatory agent during induction chemotherapy. Further studies with larger samples and longer follow-up are recommended to clarify its therapeutic relevance.

Trial registration number NCT05149339 in www.clinicaltrial.gov registered on 25/11/2021 'retrospectively registered’ with URL; https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000BKX8&selectaction=Edit&uid=U0005ZGQ&ts=98&cx=avh64j.