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Aims  Asparaginase (ASP) hypersensitivity is a well‐known challenge in the treatment of lymphoblastic malignancies. In terms of cost considerations, the cheap native   Escherichia coli   ASP, the most immunogenic form of this medication, is used in the first line in middle‐income countries. Previously, the role of the  HLA‐DRB1*07:01–DQA1*02:01–DQB1*02:02  haplotype had been established to associate with   E. coli   ASP hypersensitivity. We investigated a possible cost‐effective genetic testing method to identify patients harbouring the risk HLA haplotype in order to pave the way for safer ASP treatment.    Methods  In 241 patients with previously determined  HLA‐DRB1*07:01–DQA1*02:01–DQB1*02:02  haplotype and known ASP hypersensitivity status, 4 candidate HLA‐tagging single‐nucleotide polymorphisms (SNP)s were measured, and the performance of the different sets of these tag SNPs was evaluated.    Results  We identified a combination of 2 SNPs — rs28383172 and rs7775228 — as a tag for  HLA‐DRB1*07:01–DQA1*02:01–DQB1*02:02  haplotype with sensitivity and specificity values >95%. In line with previous findings, we found complete concordance between  HLA‐DRB1*07:01  and rs28383172. With bioinformatics methods, the results were also confirmed in the 1000 Genomes dataset in different ethnic groups.    Conclusion  Rs28383172 and rs7775228 are suitable for identifying  HLA‐DRB1*07:01–DQA1*02:01–DQB1*02:02  carriers. Compared to the rest of the population, patients with hypersensitivity‐prone genotype would benefit more from the administration of less immunogenic PEGylated ASP before the hypersensitivity evolves, incurring minimal extra cost.

british journal of clinical pharmacology

Two tagging single‐nucleotide polymorphisms to capture  HLA ‐ DRB1*07:01–DQA1*02:01–DQB1*02:02  haplotype associated with asparaginase hypersensitivity