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Published on: September 6, 2017
HLA alleles associated with asparaginase hypersensitivity in Chinese children
Gilbert T Chua1,2, Jaime S Rosa Duque1,2, Daniel Ka Leung Cheuk1,2
1Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, 1/F, New Clinical Building, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Road, Pokfulam, Hong Kong SAR, China.
Insights
Specific human leukocyte antigen (HLA) alleles, HLA-B*46:01 and DRB1*09:01, are linked to hypersensitivity reactions in Chinese children receiving asparaginase therapy for leukemia and lymphoma.
Area of Science:
- Immunogenetics
- Pharmacogenomics
- Pediatric Oncology
Background:
- Asparaginase is a critical chemotherapeutic agent for childhood hematologic malignancies.
- Hypersensitivity reactions to asparaginase can limit treatment efficacy.
- Genetic associations, specifically Human Leukocyte Antigens (HLA), with asparaginase hypersensitivity in Chinese pediatric populations are not well-established.
Abstract:
Asparaginase is an important drug to treat childhood haematological malignancies. Data on the association between human leukocyte antigens (HLA) and asparaginase hypersensitivity among Chinese are lacking. We conducted a retrospective study to identify HLA alleles associated with asparaginase hypersensitivity among Chinese children with acute lymphoblastic leukaemia (ALL), mixed phenotype leukaemia and non-Hodgkin lymphoma (NHL), who received asparaginases with HLA typing performed between 2009 and 2019. 107 Chinese patients were analysed. 66.3% (71/107) developed hypersensitivity to at least one of the asparaginases. HLA-B*46:01 (OR 3.8, 95% CI 1.4-10.1, p < 0.01) and DRB1*09:01 (OR 4.3, 95% CI 1.6-11.4, p < 0.01) were significantly associated with L-asparaginase hypersensitivities, which remained significant after adjustment for age, gender and B cell ALL [HLA-B*46:01 (adjusted OR 3.5, 95% 1.3-10.5, p = 0.02) and DRB1*09:01 (OR 4.4, 95% CI 1.6-13.3, p < 0.01)].
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