Effect of Bleomycin Hydrolase Gene Polymorphism on Late Pulmonary Complications of Treatment for Hodgkin Lymphoma.
BACKGROUND
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.


METHODS
We 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.


RESULTS
Significantly 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.


CONCLUSIONS
Besides 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.
Department of Hematology, University of Debrecen, Faculty of Medicine, Debrecen, Hungary.
Ádám
http://orcid.org/0000-0003-4181-4513
Á
Jóna
Department of Hematology, University of Debrecen, Faculty of Medicine, Debrecen, Hungary.
Zsófia
Z
Miltényi
Genomic Medicine and Bioinformatic Core Facility, Department of Biochemistry and Molecular Biology, University of Debrecen, Faculty of Medicine, Debrecen, Hungary.
Szilárd
S
Póliska
Genomic Medicine and Bioinformatic Core Facility, Department of Biochemistry and Molecular Biology, University of Debrecen, Faculty of Medicine, Debrecen, Hungary.
Bálint László
BL
Bálint
Department of Hematology, University of Debrecen, Faculty of Medicine, Debrecen, Hungary.
Árpád
Á
Illés
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001761:Bleomycin / Q000627:therapeutic use; D016022:Case-Control Studies; D003546:Cysteine Endopeptidases / Q000235:genetics*; D003606:Dacarbazine / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006689:Hodgkin Disease / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008168:Lung / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012129:Respiratory Function Tests; D014747:Vinblastine / Q000627:therapeutic use; D055815:Young Adult
D001761:Bleomycin; D014747:Vinblastine; D003606:Dacarbazine; D004317:Doxorubicin; D003546:Cysteine Endopeptidases; C031262:bleomycin hydrolase