EFFECTS OF POST-CHEMOTHERAPY DRUGS ON THE LIVER FUNCTION TESTS IN PEDIATRIC PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)

DITA PERMATASARI; NURUL AINI; RAHMI YOSMAR

doi:10.22159/ijap.2025.v17s1.09

Authors

DITA PERMATASARI Departement of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Andalas Padang-25175, Indonesia
NURUL AINI Departement of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Andalas Padang-25175, Indonesia
RAHMI YOSMAR Departement of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Andalas Padang-25175, Indonesia

DOI:

https://doi.org/10.22159/ijap.2025.v17s1.09

Keywords:

Acute lymphoblastic leukemia, Chemotherapy, Hepatotoxic, Bilirubin, AST, ALT

Abstract

Objective: Acute Lymphoblastic Leukemia (ALL) is the most common pediatric malignancy, and its treatment, which involves multiple chemotherapy phases, can lead to hepatotoxicity. This study aimed to assess the differences liver function tests based on sociodemographic profile, as well as the prevalence of hepatotoxicity, in pediatric ALL patients undergoing chemotherapy.

Methods: A retrospective analytical observational study was conducted on 52 pediatric ALL patients treated between 2020–2022. Data on sociodemographic profile, chemotherapy phases, and liver function tests were collected from medical records. Chi-Square and Fisher’s Exact tests were used for statistical analysis.

Results: The results indicated that pediatric ALL was more common in males (51.9%), with toddlers and adolescents both representing 34.6%. The maintenance chemotherapy phase was the most common (46.1%), and 84.6% of patients were classified as high-risk. There were no significant differences in bilirubin levels (total, direct, indirect) based on gender, age, chemotherapy phase, or ALL risk (p>0.05). AST levels varied by chemotherapy phase (p<0.05), but not by other factors. ALT levels differed by chemotherapy phase and ALL risk (p<0.05). Hepatotoxicity was rare, affecting only 3.9% of patients, with no significant relationship found between sociodemographic factors and hepatotoxicity (p>0.05).

Conclusion: This study highlights that liver function tests, particularly ALT and AST, varied significantly with chemotherapy phases and ALL risk but showed no differences based on gender or age. Hepatotoxicity was uncommon. Regular liver function monitoring during chemotherapy is important, especially for high-risk patients or those receiving intensive treatment.

References

DiPiro JT, Yee GC, Haines ST, Nolin TD, Ellingrod VL, Posey LM. DiPiro’s Pharmacotherapy: a Pathophysiologic Approach; 12th ed; 2023.

Mahmoud AM, Hussein OE, Hozayen WG, Abd El-Twab SM. Methotrexate hepatotoxicity is associated with oxidative stress and down-regulation of pparγ and Nrf2: protective effect of 18β-Glycyrrhetinic acid. Chem Biol Interact. 2017;270:59-72. doi: 10.1016/j.cbi.2017.04.009, PMID 28414158.

Singh A, Bhat TK, Sharma OP. Clinical biochemistry of hepatotoxicity. J Clin Toxicol. 2014;4(1). doi: 10.4172/2161-0495.s4-001.

Prasanna PL, Renu K, Valsala Gopalakrishnan A. New molecular and biochemical insights of doxorubicin-induced hepatotoxicity. Life Sci. 2020;250:117599. doi: 10.1016/j.lfs.2020.117599, PMID 32234491.

Desiandura K, Rahayu A, Wibisono FJ. Cat’s liver disease detection with SGOT and SGPT evaluation as a gold standard diagnosis. Indonesian J Trop Infect Dis. 2022;10(1):48-54. doi: 10.20473/ijtid.v10i1.32087.

Shah Nizzamani DG, Nizamani ZA, Fahim DA, Uddin Ujjan DI. Acute lymphoblastic leukemia; chromosomal abnormalities in childhood reporting at a tertiary care hospital of Sindh. Prof Med J. 2016;23(3):312-6. doi: 10.17957/TPMJ/16.3199.

Yildirim UM, Tekkesin F, Koc BS, Aydogdu S, Asarcikli F, Kilic SC. Acute complications observed during intensive chemotherapy in pediatric patients with acute lymphoblastic leukemia: single-center experience. North Clin Istanb. 2023;10(4):458-69. doi: 10.14744/nci.2022.47600, PMID 37719261.

Hasni H, Mayetti M, Novrianda D. Cryotherapy as a prophylaxis of mucositis in children with cancer undergoing chemotherapy at Dr. M. Djamil general hospital. Indonesian J Cancer. 2021;15(4):183-8. doi: 10.33371/ijoc.v15i4.828.

Silverman LB, Stevenson KE, O’Brien JE, Asselin BL, Barr RD, Clavell L. Long-term results of dana-farber cancer institute ALL consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1985-2000). Leukemia. 2010;24(2):320-34. doi: 10.1038/leu.2009.253, PMID 20016537.

Hayashi H, Makimoto A, Yuza Y. Treatment of pediatric acute lymphoblastic leukemia: a historical perspective. Cancers (Basel). 2024;16(4):723. doi: 10.3390/cancers16040723, PMID 38398113.

Brown P, Inaba H, Annesley C, Beck J, Colace S, Dallas M. Pediatric acute lymphoblastic leukemia. version 2.2020. JNCCN Journal of the National Comprehensive Cancer Network. 2020;18(1):81-112.

European Association for the Study of the Liver, Clinical Practice Guideline Panel: Chair: Panel members, EASL Governing Board representative:. EASL Clinical Practice Guidelines: drug-induced liver injury. J Hepatol. 2019;70(6):1222-61. doi: 10.1016/j.jhep.2019.02.014, PMID 30926241.

Mudd TW, Guddati AK. Management of hepatotoxicity of chemotherapy and targeted agents. Am J Cancer Res. 2021;11(7):3461-74. PMID 34354855.

Chowdhury S, Islam A, Sultana M, Mostafiz MI. Assessment of renal and liver function tests before and after induction of chemotherapy in newly diagnosed acute lymphoblastic leukemia in children. Community-Based Med J. 2022;11(1):21-6. doi: 10.3329/cbmj.v11i1.60264.

Mekonnen AT, Wondmeneh TG. Evaluation of liver function tests to identify hepatotoxicity among acute lymphoblastic leukemia patients who are receiving chemotherapy induction. Sci Rep. 2022;12(1):13215. doi: 10.1038/s41598-022-17618-w, PMID 35918381.

Islam T, Rahman AK, Hasan MK, Jahan F, Mondal MC, Ferdoushi S. Liver Function Tests in Patients of Acute Leukemia before and after Induction Chemotherapy. JBM. 2020;8(2):110-21. doi: 10.4236/jbm.2020.82009.

He X, Yao P, Li M, Liang H, Liu Y, Du S. A risk scoring model for high-dose methotrexate-induced liver injury in children with acute lymphoblastic leukemia based on gene polymorphism study. Front Pharmacol. 2021;12:726229. doi: 10.3389/fphar.2021.726229, PMID 34658865.

Qin FL, Sang GY, Zou XQ, Cheng DH. Drug-induced liver injury during consolidation therapy in childhood acute lymphoblastic leukemia as assessed for causality using the updated RUCAM. Can J Gastroenterol Hepatol. 2022;2022:5914593. doi: 10.1155/2022/5914593, PMID 35369115.

Guerra Ruiz AR, Crespo J, Lopez Martinez RM, Iruzubieta P, Casals Mercadal G, Lalana Garces M. Measurement and clinical usefulness of bilirubin in liver disease. Adv Lab Med. 2021;2(3):352-72. doi: 10.1515/almed-2021-0047, PMID 37362415.

King PD, Perry MC. Hepatotoxicity of chemotherapy. Oncologist. 2001;6(2):162-76. doi: 10.1634/theoncologist.6-2-162, PMID 11306728.

AL-Jumaili FL, Fadhil Hantoosh S, Mohammed Al-Ezzy R. Measurement of fasting blood sugar, serum total protein, serum albumin, serum total measurement of fasting blood sugar, serum total protein, serum albumin, serum total bilirubin, serum direct bilirubin, and liver function parameters for children W. Asian Adv Med Sci. 2021;2(Oct):44-9.

Hashmi SK, Navai SA, Chambers TM, Scheurer ME, Hicks MJ, Rau RE. Incidence and predictors of treatment-related conjugated hyperbilirubinemia during early treatment phases for children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2020;67(2):e28063. doi: 10.1002/pbc.28063, PMID 31736183.

Zawitkowska J, Lejman M, Zaucha Prażmo AZ, Drabko K, Płonowski M, Bulsa J. Grade 3 and 4 toxicity profiles during therapy of childhood acute lymphoblastic leukemia. In Vivo. 2019;33(4):1333-9. doi: 10.21873/invivo.11608, PMID 31280227.

Hameed Aldulaimy N, Merza Al-Araji S. The effect of acute lymphoblastic leukemia on liver functions. J Pharm Sci Res. 2019;11(11):3697-9.

Fernandez Ventureira V, Ros Arnal I, Rodriguez Martinez G, Garcia Rodriguez B, Garcia Romero R, Ubalde Sainz E. Evaluation of liver function tests in the paediatric patient. An Pediatr (Engl Ed). Engl. 2021;94(6):359-65. doi: 10.1016/j.anpede.2020.06.014, PMID 34090632.

Altalib NA, Mohialdeen SK, Chlimeran SK. Study of liver functions and some biomarkers in leukemia patients. Biomed Biotechnol Res J. 2023;7(2). doi: 10.4103/bbrj.bbrj_79_23.

Mekonnen AT, Wondmeneh TG. Evaluation of liver function tests to identify hepatotoxicity among acute lymphoblastic leukemia patients who are receiving chemotherapy induction. Sci Rep. 2022;12(1):13215. doi: 10.1038/s41598-022-17618-w, PMID 35918381.

Ramadori G, Cameron S. Effects of systemic chemotherapy on the liver. Ann Hepatol. 2010;9(2):133-43. doi: 10.1016/S1665-2681(19)31651-5, PMID 20526005.

Bahirwani R, Reddy KR. Drug-induced liver injury due to cancer chemotherapeutic agents. Semin Liver Dis. 2014;34(2):162-71. doi: 10.1055/s-0034-1375957, PMID 24879981.

Sleurs C, Musoro J, Rowsell A, Kicinski M, Suciu S, Chantziara S. Sociodemographic and medical determinants of quality of life in long-term childhood acute lymphoblastic leukemia survivors enrolled in eortc clg studies. Cancers (Basel). 2021;14(1):152. doi: 10.3390/cancers14010152, PMID 35008314.

Jannat M, Morshed AA, Anwer S, Islam S. Effect of chemotherapy on liver function during induction of remission in children with acute lymphoblastic leukemia receiving standard protocol. J Dhaka Med Coll. 2021;29(1):33-7. doi: 10.3329/jdmc.v29i1.51168.

Bresters D, BGP K, RL M, EC Van D, MV den H. Hepatic late adverse effects after antineoplastic treatment for childhood cancer. Cochrane Child Cancer Group. 2011;7:1-64.

Bhutadiya VL, Mistry KN. A review on bioactive phytochemicals and it’s mechanism on cancer treatment and prevention by targeting multiple cellular signaling pathways. Int J Pharm Pharm Sci. 2021;13(12):15-9. doi: 10.22159/ijpps.2021v13i12.42798.

Hoofnagle JH, Bjornsson ES. Drug-induced liver injury types and phenotypes. N Engl J Med. 2019;381(3):264-73. doi: 10.1056/NEJMra1816149, PMID 31314970.

Hikmat AA, Andarsini MR, Setyoboedi B, Larasati MC, Cahyadi A, Ugrasena ID. Risk factors for hepatotoxicity from L-asparaginase chemotherapy in children with acute lymphoblastic leukemia. Pharmacogn J. 2022;14(6):921-7.

Burke PW, Hoelzer D, Park JH, Schmiegelow K, Douer D. Managing toxicities with asparaginase-based therapies in adult all: summary of an esmo open-cancer horizons roundtable discussion. ESMO Open. 2020;5(5):e000858. doi: 10.1136/esmoopen-2020-000858, PMID 33037033.

Daripa S, Banerjee S, Sadhya A, Bera A. Toxicity and treatment outcome of accelerated fractionation radiotherapy versus conventional fractionated concomitant chemoradiation in locally advanced cervical carcinoma: a prospective study. Asian J Pharm Clin Res. 2022;15(8):127-31. doi: 10.22159/ajpcr.2022.v15i8.45120.