Pegasparaginase-induced hepatotoxicity in patients with acute lymphocytic leukemia in the Saudi population - A retrospective cohort study

Sep 30, 2026

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Acute lymphocytic leukemia (ALL) treated with pegasparaginase (PEG-ASP) can cause clinically relevant hepatotoxicity, yet limited evidence exists in Saudi patients. This retrospective cohort study reviewed records of pediatric and adult ALL patients who received at least one PEG-ASP dose between 2014 and 2021, grading hepatotoxicity by CTCAE v5. Among 368 patients, overall hepatotoxicity was 38.8% (95% CI 33.9–43.8), higher in pediatric than adult patients. Multiple logistic regression identified bilirubin level, hyperdiploidy, PEG-ASP dose, vincristine exposure, and elevated liver enzymes as risk factors.

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CategoryHealthcare

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® Observational Study Pegasparaginase-induced hepatotoxicity inpatients with acute lymphocytic leukemia in the Saudi population A retrospective cohort study Ghadah H. Alshehri, MSc, PhDa , Nada Alsuhebany, BSPharm, PharmD, BCOPb ,c ,d , Mira M. Alhumaid, PharmDa , Reema H. Alanazi, PharmDa , Amani A. Alsetri, PharmDa , Shaher Bahakeem, MSce , Ghaliah A. Aldamegh, PharmDb , Dalal T. Alangari, PharmDb , Alaa A. Alhubaishi, BSc Pharm, PharmDa ,* , Salwa S. Zghebi, MPhil, PhDf,g , Abdullah M. Alrajhi, BSc Pharm, PharmD, MHEP, BCOPh , i | Abstract
Acute lymphocytic leukemia (ALL) is a hematologic malignancy commonly treated with pegasparaginase (PEG-ASP) . Limited data exist on PEG-ASP-induced hepatotoxicity in the Saudi population; therefore, this study aimed to determine the rate and risk factors of PEG-ASP-induced hepatotoxicity in Saudi pediatric and adult ALL patients. This retrospective cohort study reviewed the records of ALL patients who had been treated with or received at least 1 dose of PEG-ASP between 2014 and 2021. Hepatotoxicity was graded using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5. Bivariate and multiple logistic regression analyses were used to analyze the relationships between the variables and the risk of PEG-ASP-induced hepatotoxicity. A total of 368 patients were included in the study, with an overall hepatotoxicity rate of 38.8 (95% CI = 33.9–43.8) per 100 patients. Hepatotoxicity was observed in 35.7%(n = 117/328) of pediatric patients and 7.6%(n = 25/328) of adult patients. Risk factors of hepatotoxicity were identified: bilirubin level (odds ratio = 1.324, 95% CI = 1.089–1.610), presence of hyperdiploidy (OR = 1.456, 95% CI = 1.112–1.907), PEG-ASP dose (OR = 1.287, 95% CI = 1.021–1.623), and vincristine administration (OR = 1.398, 95% CI = 1.087–1.798) . Additionally, the liver function test levels included alanine aminotransferase (OR = 1.512, 95% CI = 1.198–1.909), aspartate aminotransferase (OR = 1.445, 95% CI = 1.156–1.806), and gamma-glutamyl transferase (OR = 1.367, 95% CI = 1.089– 1.716) . PEG-ASP-induced hepatotoxicity poses a significant risk to Saudi patients with ALL. Further studies are needed to identify additional risk factors and improve the management of hepatotoxicity in ALL patients receiving PEG-ASP. | | --- | | Abbreviations: ALL = acute lymphocytic leukemia, ALT = alanine aminotransferase, AST = aspartate aminotransferase, BMI = body mass index, BSA = body surface area, CalPEG-ASP = calaspargase pegol, CNS = central nervous system, CTCAE = common terminology criteria for adverse events, DNA = deoxyribonucleic acid, EQUATOR = enhancing the quality and transparency of health research, FDA = U.S. Food and Drug Administration, FISH = fluorescence in situ hybridization, GGT = gamma–glutamyl transferase, GMALL = German Multicenter Study Group for Adult ALL, GSTT1/ GSTM1 = glutathione S-transferase theta 1/ mu 1, LFT = liver function test, MLL = mixed-lineage leukemia, MNGHA = Ministry of National Guard Health Affairs, PEGASP = pegasparaginase, Ph+/Ph− = Philadelphia chromosome positive/negative, STROBE = strengthening the reporting of observational studies in epidemiology, UGT1A1 = uridine diphosphate glucuronosyltransferase 1A1, ULN = upper limit of normal. | | Keywords: acute lymphocytic leukemia, hepatotoxicity, pegasparaginase, Saudi population | The research was funded by the Princess Nourah bint Abdulrahman University Researchers Support Initiative (PNURSP2025R352), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia. The authors have no conflicts of interest to disclose. The data that support the findings of this study are available from a third party, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are available from the authors upon reasonable request and with permission of the third party. The views expressed in

FAQs

What was the study objective regarding PEG-ASP hepatotoxicity in Saudi ALL patients?

To determine the rate and risk factors of pegasparaginase (PEG-ASP)-induced hepatotoxicity in Saudi pediatric and adult patients with acute lymphocytic leukemia.

How were hepatotoxicity outcomes measured in the study?

Hepatotoxicity was graded using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.

Which factors were identified as risk factors for PEG-ASP-induced hepatotoxicity?

Bilirubin level, presence of hyperdiploidy, PEG-ASP dose, vincristine administration, and elevated liver function test levels including ALT, AST, and GGT.

Sep 30, 2026

Uploaded by jay