Fokkema, C. (Cathelijne) (2019) PEG-asparaginase and Hepatotoxicity in the HOVON 100 trial. thesis, Medicine.
Full text available on request.Abstract
Acute Lymphoblastic Leukaemia (ALL) is a malignant disease that originates from B- or T-lymphocyte precursors in the bone marrow. Overall survival has greatly increased in recent years due to treatment protocols using multi-agent chemotherapy. An important component in this treatment protocol is asparaginase, an anti-leukemic drug. Asparaginase depletes asparagine from peripheral blood. Asparagine is a crucial enzyme which leukemic cells require for cell division. Its, depletion results in reduced protein synthesis which eventually leads to apoptosis. Several side-effects have been reported with asparaginase treatment, the most common side-effect in adults is hepatotoxicity. Despite a lot of data confirming the high toxicity rate of asparaginase in adult patients there is lack of research identifying risk factors for developing hepatotoxicity. Practical issues related to continuation of PEG-asparaginase after severe asparaginase-induced hepatotoxicity and the relation between overall survival and hepatotoxicity, has not been elucidated. Identifying risk factors may help in guiding preventive measures. Also we aim to establish recommendations regarding asparaginase-induced hepatotoxicity and further PEG-asparaginase treatment in the adult ALL regimen. We retrospectively analysed hepatotoxicity in the Dutch-Belgian HOVON-100 ALL study-cohort (H100) where 376 adult patients were included. Of these patients, 45.9 % developed hepatotoxicity of whom 25% seemed to be related to PEG-asparaginase. None of these patients developed fulminant liver failure. The incidence of hepatotoxicity was most prominent during the first induction chemotherapy cycle (52%) in adults younger than 40 years of age. During this first cycle of chemotherapy hepatotoxicity was the most common reason to stop (43.6%) or delay (62.5%) PEG-asparaginase treatment during the following courses of chemotherapy in this trial. Besides asparaginase treatment during induction no other significant risk factors ( such as age, BSA, baseline liver functions) for developing hepatotoxicity could be established. Developing hepatotoxicity, had no negative effect on survival. Recurrent asparaginase-induced hepatotoxicity occurred in only 17% of all patients experiencing hepatotoxicity during induction. Therefore, stopping or reducing PEG-asparaginase administration due to hepatotoxicity might not be indicated.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Bellido dr. M. (UMCG) |
| Supervisor name: | Rijneveld, Dr. A.W. and Department of hematology, Erasmus Medical Center Rotterdam |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:52 |
| Last Modified: | 25 Jun 2020 10:52 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/1304 |
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