ADVERSE EFFECTS OF L-ASPARAGINASE IN THE TREATMENT OF ACUTE
LYMPHOBLASTIC LEUKEMIA
Wafa Chenbah1, Nesrine ben Sayed1, Emna Bouslama1, Bechir Achour2, Bouraoui Elouni3, Yosra ben
Youssef2 and Abderrahim Khelif2
(1) Departement of Hematology Farhat Hached Hospital, sousse, Tunisia, (2) Departement of
Hematology Farhat Hached Hospital, Sousse, Tunisia, (3) Departement of Pharmacology Farhat Hached
Hospital, Sousse, Tunisia
Asparginase is a bacterial enzyme that converts aspargine to aspartic acid widely used in the
treatment of ALL. It can cause several adverse drug reactions: hypersensitivity, pancreatitis,
thrombosis, hepatic and hyperglycemia.
Objectives of the work: - Determine the epidemiological, clinical and evolutionary profile of
asparginase toxicity in the treatment of ALL. -Analyze the factors associated with the
occurrence of adverse effects of L-asparginase. -Evaluate the impact of adverse effects on the
prognosis of the disease. -Analyze the factors influencing the course of the disease.
Patients and Methods: We carried out a retrospective descriptive study carried out in the
clinical hematology service in collaboration with the regional pharmacovigilance center of
Sousse including patients treated with L-asparginase for ALL and who had adverse effects
(01/01 / 2008 to 12/31/2019). Drug causality was assessed using the Naranjo score and we
retained that the side effects labeled probable and definite. A pre-established collection sheet
is used to collect information about the patient, L-asparginase and the event. We performed
a statistical analysis on SPSS. In the multivariate analysis we used binary logistic regression to
study the factors independently correlated with the occurrence of asparginase-induced
adverse effects, as well as the factors influencing the course of the disease. We have
introduced only variables that had a p-value <0.2 in the univariate study.
Results: A total of 208 patients were included in our study. The average age was 15 years (1-
66 years old) with a gender-ratio (M / F) 1.14. In our study, all of our patients were treated
with asparginase for ALL. The most frequently used chemotherapy protocol was EORTC for
77% of patients followed by saint jude protocol for 11% of patients and then AUGMENTED
BFM for 8% of patients and lastly GRALL for 4% of patients. 25% of the study population
experienced adverse effects from L-asparginase. The majority of adverse reactions that
occurred were noted during the induction phase of chemotherapy with 52% of cases. The
adverse effects selected were of the following types: Immediate hypersensitivity (n = 35),
thrombotic accidents (n = 8), hepatic damage (n = 7), pancreatic damage (n = 4) and metabolic
type of hyperglycemia (n = 2). Four patients presented with multisystem involvement. We
found a statistically significant relationship between the occurrence of cerebral thrombosis,
hypersensitivity and age under 18 years with p = 0.01 and p = 0.02, respectively. We also found
a statistically significant relationship between the different age groups, the presence or
absence of side effects, the occurrence of hyperglycemia, pancreatic involvement and disease
progression with p <0.01.
Conclusion: It is important that any doctor using asarginase is aware of the likelihood of
possible treatment-related side effects. This invites to do a rigorous monitoring and rapid
therapeutic care.
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