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Abstract
BackgroundBleomycin hydrolase (BLMH), an enzyme that inactivates bleomycin, may be a potential candidate that could influence pulmonary function in ABVD (doxorubicin, bleomycin, vinblastin, dacarbasine)–treated Hodgkin lymphoma (HL) patients.Patients and MethodsWe hypothesized that the BLMH gene SNP A1450G (rs1050565) influences BLMH activity and late pulmonary toxicity. St. George Respiratory Questionnaire, lung scintigraphy and spirometry were used to determine lung function. TaqMan genotyping assay was used to determine genotype distribution of 131 previously treated HL patients.ResultsSignificantly more favorable results were seen in the wild-type A/A genotype group than those in the group containing the mutated allele: A/G+G/G in retrospective pulmonary tests of ABVD treated patients.ConclusionBesides limitations of the current study, bleomycin pharmacokinetics should be further evaluated in patients with BLMH variations, hence identify those cases even in the frontline setting, where bleomycin should be omitted and replaced with targeted therapy.
Highlights
The survival rates of Hodgkin lymphoma (HL) patients have significantly improved over the past decades
Besides limitations of the current study, bleomycin pharmacokinetics should be further evaluated in patients with Bleomycin hydrolase (BLMH) variations, identify those cases even in the frontline setting, where bleomycin should be omitted and replaced with targeted therapy
Single nucleotide polymorphisms (SNP) A1450G is located in the C-terminal region, which is responsible for the enzymatic activity [6,7], and this SNP leads to the substituition of isoleucin as amino acid residue 443 by valine, changing aminopeptidase activity
Summary
Bleomycin hydrolase (BLMH), an enzyme that inactivates bleomycin, may be a potential candidate that could influence pulmonary function in ABVD (doxorubicin, bleomycin, vinblastin, dacarbasine)–treated Hodgkin lymphoma (HL) patients
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