The Association of Parathyroid Hormone Related Protein and Vitamin D Level with Serum Calcium Ion in Acute Leukemia Patients

Niniek Wiendayanthi, MI. Diah Pramudianti, Yuwono Hadisuparto


Acute leukemia is bone marrow clonal cell malignancy. One of its complications is hypercalcemia. Parathyroid Hormone-Related Protein (PTHrP) activities involve the regulation of Calcium (Ca) metabolism. Vitamin D is a steroid involved in Ca homeostasis and bone mineralization. This study aimed to analyze PTHrP and vitamin D levels with serum calcium ion in acute leukemia. A cross-sectional study was performed in Clinical Pathology Dr. Moewardi General Hospital Surakarta between July and August 2019, consisting of 41 subjects with new acute leukemia who were diagnosed based on bone marrow puncture and or immunophenotyping result. The cut-off value of Ca ion serum and PTHrP level were determined with a Receiver Operating Curve (ROC). The data were analyzed with a 2x2 table, followed by multivariate logistic regression analysis, and p<0.05 was considered significant. Statistical analysis showed the median age of 25 (2-68) years, 23 (56.10%) ALL, and 18 (43.90%) non-ALL patients. The median of Ca ion and PTHrP were 1.08 (0.84-1.21) mmol/l and 307.52 (20.77-1104.26) pg/mL, respectively. The mean level of vitamin D was 26.45±11.40 ng/mL. Bivariate analysis showed that PTHrP levels ≥ 110.09 pg/mL and vitamin D ≥ 20 ng/mL were related to serum Ca ion ≥ 1.07 mmol/l (PR 4.675; 95% CI: 1.211-18.041; p=0.021 and PR 5.143; 95% CI: 1.279-20.677; p=0.017). Multivariate analysis showed that PTHrP ≥ 110.09 pg/mL and vitamin D ≥ 20 ng/mL were associated with serum Ca ion ≥1.07 mmol/l. There was a significant association between PTHrP, vitamin D level, and serum Ca ion in acute leukemia patients.


Acute leukemia, hypercalcemia, parathyroid hormone-related protein, vitamin D

Full Text:



de Vos J, Hassan S, Sikorska J. ABC of clinical hematology. Fourth Ed., Provan D, editor. London, Wiley, 2018; 33–39.

Rahmadin B, Wahid I, Yaswir R. Artikel penelitian profil penderita leukemia mieloblastik akut di bagian penyakit. J Kesehat Andalas, 2017; 6(3): 495–501.

Merino A, Boldú L, Ermens A. Acute myeloid leukemia: How to combine multiple tools. Int J Lab Hematol, 2018; 40: 109–19.

Goldner W. Cancer-related hypercalcemia. Am J Nurs, 2016; 12(5): 426-32.

Shu ST, Dirksen WP, Weibaecher KN, Rosol TJ. Mechanisms of humoral hypercalcemia of malignancy in leukemia/lymphoma. intechopen, 2018; 181–206.

Mundy GR, Edwards JR. PTH-Related Peptide (PTHrP) in hypercalcemia. 2008; 672–5.

Mirrakhimov AE. Hypercalcemia of malignancy: An update on pathogenesis and management. N Am J Med Sci, 2015; 7(11): 483–93.

Tebben PJ, Singh RJ, Kumar R. Vitamin D-mediated hypercalcemia: Mechanisms, diagnosis, and treatment. Endocr Rev, 2016; 37(5): 521–47.

Kulling PM, Olson KC, Olson TL, Feith DJ, Loughran TP. Vitamin D in hematological disorders and malignancies. Eur J Haematol, 2017; 98(3): 187–97.

Santoyo-Sánchez A, Ramos-Peñafiel CO, Martínez-Tovar A, Olarte-Carrillo I, Collazo-Jaloma J, et al. The age and sex frequencies of patients with leukemia seen in two reference centers in the metropolitan area of Mexico City. Gac Med Mex, 2016; 152(2): 208–12.

Hasanbegovic E, Begic N, Hasanbegovic S, Begic Z. Socio-demographic characteristics of patients with diagnosis of Leukemia in Bosnia and Herzegovina during six-year period. Mater Socio Medica, 2016; 28(6): 473.

Sultan S, Zaheer HA, Irfan SM, Ashar S. Demographic, and clinical characteristics of adult acute myeloid leukemia-tertiary care experience. Asian Pacific J Cancer Prev, 2016; 17(1): 357–60.

Allahyari A, Hashemi SM, Nazemian F, Karimi M, Kazemi MR, Sadeghi M. The relationship between risk factors and survival in adult acute lymphoblastic leukemia. Int J Cancer Manag, 2016; 9(4): e5045.

Naz A. Vitamin D levels in patients of acute leukemia before and after remission-induction therapy. Pakistan J Med Sci, 2012; 29(1): 10–4.

Moayeri H, Oloomi Z, Sambo SA. A cross-sectional study to determine the prevalence of calcium metabolic disorder in malignant childhood cancers in patients admitted to the Pediatric Ward of Vali-Asr Hospital. Acta Med Iran, 2011; 49(12): 818–23.

Lee HJ, Muindi J, Wei T, Wilding G, Ford LA, Sait S, et al. Subnormal vitamin D levels are associated with adverse outcome in newly-diagnosed similarly-treated adult Acute Myeloid Leukemia (AML) patients. Blood [Internet]. 2010; 116(21): 1041.

Afridi HI, Kazi TG, Talpur FN. Correlation of calcium and magnesium levels in the biological samples of different types of acute leukemia children. Biol Trace Elem Res, 2018; 1–12.

McKay C, Furman WL. Hypercalcemia complicating childhood malignancies. Cancer. 1993; 72(1): 256–60.

Milionis HJ, Bourantas CL, Siamopoulos KC, Elisaf MS. Acid-base and electrolyte abnormalities in patients with acute leukemia. Am J Hematol, 1999; 62(4): 201–7.

Inukai TT, Hirose K, Inaba T, Kurosawa H, Hama A, et al. Hypercalcemia in childhood acute lymphoblastic leukemia: Frequent implication of parathyroid hormone-related peptide and E2A-HLF from translocation 17;19. Leukemia, 2007; 21(2): 288–96.

Donovan PJ, Achong N, Griffin K, Galligan J, Pretorius CJ, McLeod DSA. PTHrP-mediated hypercalcemia: Causes and survival in 138 patients. J Clin Endocrinol Metab, 2015; 100(5): 2024–9.

Kingsley U, Agu C, Nwosu T. Critical review of hypercalcemia. J Med Allied Sci, 2017; 7(1): 3.

Demirsoy U, Sarper N, Aylan Gelen S, Zengin E, Kum T, Demir H. The association of oral vitamin D and calcium supplementation with bone mineral density in pediatric acute lymphoblastic leukemia patients. J Pediatr Hematol Oncol, 2017; 39(4): 287–92.



  • There are currently no refbacks.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.