Dataset Information

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

ABSTRACT:

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.

Patients and 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.

Conclusion

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.

SUBMITTER: Jona A

PROVIDER: S-EPMC4915614 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Jóna Ádám Á Miltényi Zsófia Z Póliska Szilárd S Bálint Bálint László BL Illés Árpád Á

PloS one 20160621 6

<h4>Background</h4>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.<h4>Patients and methods</h4>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. ...[more]

PMID: 27327270

Similar Datasets

Project description:ImportanceContemporary North American trials for children with Hodgkin lymphoma (HL) have decreased radiation therapy (RT) use and increased pharmacologic cardioprotection but also increased the cumulative doxorubicin dose, making overall treatment consequences for late cardiac toxic effects uncertain.ObjectiveTo estimate the risk of cardiac toxic effects associated with treatments used in modern pediatric HL clinical trials.Design, setting, and participantsFor this cohort study, Fine and Gray models were fitted using survivors in the Childhood Cancer Survivor Study who were diagnosed with HL between January 1, 1970, and December 31, 1999, and were followed for a median of 23.5 (range, 5.0-46.3) years. These models were applied to the exposures in the study population to estimate the 30-year cumulative incidence of cardiac disease. The study population comprised patients with intermediate-risk or high-risk HL treated in 4 consecutive Children's Oncology Group clinical trials from September 2002 to October 2022: AHOD0031, AHOD0831, AHOD1331, and S1826. Data analysis was performed from April 2020 to February 2023.ExposuresAll patients received chemotherapy including doxorubicin, and some patients received mediastinal RT, dexrazoxane, or mediastinal RT and dexrazoxane.Main outcomes and measuresEstimated 30-year cumulative incidence of grade 3 to 5 cardiac disease.ResultsThe study cohort comprised 2563 patients, with a median age at diagnosis of 15 (range, 1-22) years. More than half of the patients were male (1357 [52.9%]). All 2563 patients received doxorubicin, 1362 patients (53.1%) received mediastinal RT, and 307 patients (12.0%) received dexrazoxane. Radiation therapy use and the median mean heart dose among patients receiving RT decreased, whereas the planned cumulative dose of doxorubicin and use of dexrazoxane cardioprotection increased. For patients treated at age 15 years, the estimated 30-year cumulative incidence of severe or fatal cardiac disease was 9.6% (95% CI, 4.2%-16.4%) in the AHOD0031 standard treatment group (enrolled 2002-2009), 8.6% (95% CI, 3.8%-14.9%) in the AHOD0831 trial (enrolled 2009-2012), 8.2% (95% CI, 3.6%-14.3%) in the AHOD1331 trial (enrolled 2015-2019), and 6.2% (95% CI, 2.7%-10.9%) in the S1826 trial (enrolled 2019-2022), whereas the expected rate in an untreated population was 5.0% (95% CI, 2.1%-9.3%). Despite the estimated reduction in late cardiac morbidity, the frequency of recommended echocardiographic screening among survivors will increase based on current guidelines.Conclusions and relevanceIn this cohort study of sequential HL trials, reductions in the proportion of children receiving mediastinal RT and increases in dexrazoxane use were estimated to offset the increased doxorubicin dose and produce a net reduction in late cardiac disease. Further studies on dexrazoxane are warranted to confirm whether its role in reducing cardiac toxic effects is maintained long term. These findings suggest that survivorship follow-up guidelines should be refined to align with the risks associated with treatment.

Dataset Information

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

Background

Patients and methods

Results

Conclusion

Publications

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

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