EFFECT OF BLEOMYCIN HYDROLASE GENE POLYMORPHISM ON LATE PULMONARY COMPLICATIONS OF TREATING HODGKIN LYMPHOMA
(Abstract release date: 05/21/15)
EHA Library. Jóna Á. 06/14/15; 103410; S809
Ádám Jóna
Contributions
Contributions
Abstract
Abstract: S809
Type: Oral Presentation
Presentation during EHA20: From 14.06.2015 09:00 to 14.06.2015 09:15
Location: Room Lehar 3 + 4
Background
Bleomycin induced pulmonary toxicity occurs in 20-46% of Hodgkin lymphoma (HL) patients, treated with ABVD (doxorubicin, bleomycin, vinblastin, dacarbasine) regimen. Bleomycin hydrolase (BLMH), an enzyme that inactivates bleomycin, may be a potential candidate that influences pulmonary function. Single nucleotide polymorphisms (SNP) of the BLMH gene have been investigated previously in testicular germ-cell cancer (TC) patients in parallel to survival data. Interestingly, homo- and heterozygous variants of BLMH gene SNP A1450G were found to significantly affect survival of TC patients. Yet, there is no available data of BLMH SNPs and bleomycin induced pulmonary toxicity in correlation with HL patients.
Aims
We hypothesized, that BLMH gene SNP A1450G (rs1050565) influences BLMH activity and by an altered metabolism of bleomycin, differences could be seen at the risk of bleomycin induced toxicity appearance.
Methods
Pulmonary functions of previously treated HL patients have been collected by using St. George Respiratory Questionnaire (SGRQ), dynamic inhalation lung scintigraphy and spirometry at the Department of Hematology, University of Debrecen, retrospectively. After informed consent of these patients genomic DNA was isolated from peripheral blood samples and TaqMan genotyping assay was used to determine genotype distribution. Local Research Ethics Committee approved this investigation.
Results
A total of 131 patient samples have been collected of previously treated HL patients, with a median age of 29 years (14-73), median time elapsed since treatment completion was 11 years (1-44). Genotype frequency was found as follows: A/A 55.0%, A/G 33.6%, G/G 11.5%, where A is the wild allele (71.8%) and G is the mutated allele (28.2%). Our results are comparable to the NCBI SNP database for SNP A1450G. Patients were subdivided into subgroups containing the mutated allele: A/G+G/G (45.1%) and those homogenous for the wild allele: A/A (55.0%). All bleomycin treated patients (n=102) had more favorable lung function test result in the wild A/A genotype group, with significant difference in the forced vital capacity results (FVC), p=0.041. When narrowing patients to those who received only ABVD regimen (n=68), significantly more favorable results were seen in the wild A/A genotype group with every investigated test method (SGRQ score: p=0.035, lung scintigraphy results: p=0.045, spirometry results: FVC: p=0.020; forced expiratory volume in 1 s (FEV1): p=0.028). Univariate analysis also confirmed these results. As control group (n=29), patients treated with agents excluding bleomycin were tested with no significant differences between the A/G+G/G and A/A groups. Other factors (smoking, age, bleomycin dose, chest irradiation, kidney function, use of colony stimulating factors) that could potentially affect lung function were equally represented in all investigated subgroups.
Summary
BLMH gene polymorphism significantly distinguished in retrospective pulmonary test results of ABVD treated patients. Based on these results prospective trials could be designed to further evaluate its role in pulmonary toxicity of treating HL, and thus treatment could be adjusted individually. One of its potential roles could be to identify those cases even in the frontline setting, where brentuximab vedotin should be administered instead of bleomycin, either in the standard care or considering expense issues. Patients with multiple risk factors for lung toxicity should be particularly considered for this test method. Eventually, life expectancy and quality of life of HL patients wouldn’t remarkably differ from the untreated healthy population.
Session topic: Progess in Hodgkin lymphoma therapy: Incorporation of novel agents and reduction of side effects
Type: Oral Presentation
Presentation during EHA20: From 14.06.2015 09:00 to 14.06.2015 09:15
Location: Room Lehar 3 + 4
Background
Bleomycin induced pulmonary toxicity occurs in 20-46% of Hodgkin lymphoma (HL) patients, treated with ABVD (doxorubicin, bleomycin, vinblastin, dacarbasine) regimen. Bleomycin hydrolase (BLMH), an enzyme that inactivates bleomycin, may be a potential candidate that influences pulmonary function. Single nucleotide polymorphisms (SNP) of the BLMH gene have been investigated previously in testicular germ-cell cancer (TC) patients in parallel to survival data. Interestingly, homo- and heterozygous variants of BLMH gene SNP A1450G were found to significantly affect survival of TC patients. Yet, there is no available data of BLMH SNPs and bleomycin induced pulmonary toxicity in correlation with HL patients.
Aims
We hypothesized, that BLMH gene SNP A1450G (rs1050565) influences BLMH activity and by an altered metabolism of bleomycin, differences could be seen at the risk of bleomycin induced toxicity appearance.
Methods
Pulmonary functions of previously treated HL patients have been collected by using St. George Respiratory Questionnaire (SGRQ), dynamic inhalation lung scintigraphy and spirometry at the Department of Hematology, University of Debrecen, retrospectively. After informed consent of these patients genomic DNA was isolated from peripheral blood samples and TaqMan genotyping assay was used to determine genotype distribution. Local Research Ethics Committee approved this investigation.
Results
A total of 131 patient samples have been collected of previously treated HL patients, with a median age of 29 years (14-73), median time elapsed since treatment completion was 11 years (1-44). Genotype frequency was found as follows: A/A 55.0%, A/G 33.6%, G/G 11.5%, where A is the wild allele (71.8%) and G is the mutated allele (28.2%). Our results are comparable to the NCBI SNP database for SNP A1450G. Patients were subdivided into subgroups containing the mutated allele: A/G+G/G (45.1%) and those homogenous for the wild allele: A/A (55.0%). All bleomycin treated patients (n=102) had more favorable lung function test result in the wild A/A genotype group, with significant difference in the forced vital capacity results (FVC), p=0.041. When narrowing patients to those who received only ABVD regimen (n=68), significantly more favorable results were seen in the wild A/A genotype group with every investigated test method (SGRQ score: p=0.035, lung scintigraphy results: p=0.045, spirometry results: FVC: p=0.020; forced expiratory volume in 1 s (FEV1): p=0.028). Univariate analysis also confirmed these results. As control group (n=29), patients treated with agents excluding bleomycin were tested with no significant differences between the A/G+G/G and A/A groups. Other factors (smoking, age, bleomycin dose, chest irradiation, kidney function, use of colony stimulating factors) that could potentially affect lung function were equally represented in all investigated subgroups.
Summary
BLMH gene polymorphism significantly distinguished in retrospective pulmonary test results of ABVD treated patients. Based on these results prospective trials could be designed to further evaluate its role in pulmonary toxicity of treating HL, and thus treatment could be adjusted individually. One of its potential roles could be to identify those cases even in the frontline setting, where brentuximab vedotin should be administered instead of bleomycin, either in the standard care or considering expense issues. Patients with multiple risk factors for lung toxicity should be particularly considered for this test method. Eventually, life expectancy and quality of life of HL patients wouldn’t remarkably differ from the untreated healthy population.
Session topic: Progess in Hodgkin lymphoma therapy: Incorporation of novel agents and reduction of side effects
Abstract: S809
Type: Oral Presentation
Presentation during EHA20: From 14.06.2015 09:00 to 14.06.2015 09:15
Location: Room Lehar 3 + 4
Background
Bleomycin induced pulmonary toxicity occurs in 20-46% of Hodgkin lymphoma (HL) patients, treated with ABVD (doxorubicin, bleomycin, vinblastin, dacarbasine) regimen. Bleomycin hydrolase (BLMH), an enzyme that inactivates bleomycin, may be a potential candidate that influences pulmonary function. Single nucleotide polymorphisms (SNP) of the BLMH gene have been investigated previously in testicular germ-cell cancer (TC) patients in parallel to survival data. Interestingly, homo- and heterozygous variants of BLMH gene SNP A1450G were found to significantly affect survival of TC patients. Yet, there is no available data of BLMH SNPs and bleomycin induced pulmonary toxicity in correlation with HL patients.
Aims
We hypothesized, that BLMH gene SNP A1450G (rs1050565) influences BLMH activity and by an altered metabolism of bleomycin, differences could be seen at the risk of bleomycin induced toxicity appearance.
Methods
Pulmonary functions of previously treated HL patients have been collected by using St. George Respiratory Questionnaire (SGRQ), dynamic inhalation lung scintigraphy and spirometry at the Department of Hematology, University of Debrecen, retrospectively. After informed consent of these patients genomic DNA was isolated from peripheral blood samples and TaqMan genotyping assay was used to determine genotype distribution. Local Research Ethics Committee approved this investigation.
Results
A total of 131 patient samples have been collected of previously treated HL patients, with a median age of 29 years (14-73), median time elapsed since treatment completion was 11 years (1-44). Genotype frequency was found as follows: A/A 55.0%, A/G 33.6%, G/G 11.5%, where A is the wild allele (71.8%) and G is the mutated allele (28.2%). Our results are comparable to the NCBI SNP database for SNP A1450G. Patients were subdivided into subgroups containing the mutated allele: A/G+G/G (45.1%) and those homogenous for the wild allele: A/A (55.0%). All bleomycin treated patients (n=102) had more favorable lung function test result in the wild A/A genotype group, with significant difference in the forced vital capacity results (FVC), p=0.041. When narrowing patients to those who received only ABVD regimen (n=68), significantly more favorable results were seen in the wild A/A genotype group with every investigated test method (SGRQ score: p=0.035, lung scintigraphy results: p=0.045, spirometry results: FVC: p=0.020; forced expiratory volume in 1 s (FEV1): p=0.028). Univariate analysis also confirmed these results. As control group (n=29), patients treated with agents excluding bleomycin were tested with no significant differences between the A/G+G/G and A/A groups. Other factors (smoking, age, bleomycin dose, chest irradiation, kidney function, use of colony stimulating factors) that could potentially affect lung function were equally represented in all investigated subgroups.
Summary
BLMH gene polymorphism significantly distinguished in retrospective pulmonary test results of ABVD treated patients. Based on these results prospective trials could be designed to further evaluate its role in pulmonary toxicity of treating HL, and thus treatment could be adjusted individually. One of its potential roles could be to identify those cases even in the frontline setting, where brentuximab vedotin should be administered instead of bleomycin, either in the standard care or considering expense issues. Patients with multiple risk factors for lung toxicity should be particularly considered for this test method. Eventually, life expectancy and quality of life of HL patients wouldn’t remarkably differ from the untreated healthy population.
Session topic: Progess in Hodgkin lymphoma therapy: Incorporation of novel agents and reduction of side effects
Type: Oral Presentation
Presentation during EHA20: From 14.06.2015 09:00 to 14.06.2015 09:15
Location: Room Lehar 3 + 4
Background
Bleomycin induced pulmonary toxicity occurs in 20-46% of Hodgkin lymphoma (HL) patients, treated with ABVD (doxorubicin, bleomycin, vinblastin, dacarbasine) regimen. Bleomycin hydrolase (BLMH), an enzyme that inactivates bleomycin, may be a potential candidate that influences pulmonary function. Single nucleotide polymorphisms (SNP) of the BLMH gene have been investigated previously in testicular germ-cell cancer (TC) patients in parallel to survival data. Interestingly, homo- and heterozygous variants of BLMH gene SNP A1450G were found to significantly affect survival of TC patients. Yet, there is no available data of BLMH SNPs and bleomycin induced pulmonary toxicity in correlation with HL patients.
Aims
We hypothesized, that BLMH gene SNP A1450G (rs1050565) influences BLMH activity and by an altered metabolism of bleomycin, differences could be seen at the risk of bleomycin induced toxicity appearance.
Methods
Pulmonary functions of previously treated HL patients have been collected by using St. George Respiratory Questionnaire (SGRQ), dynamic inhalation lung scintigraphy and spirometry at the Department of Hematology, University of Debrecen, retrospectively. After informed consent of these patients genomic DNA was isolated from peripheral blood samples and TaqMan genotyping assay was used to determine genotype distribution. Local Research Ethics Committee approved this investigation.
Results
A total of 131 patient samples have been collected of previously treated HL patients, with a median age of 29 years (14-73), median time elapsed since treatment completion was 11 years (1-44). Genotype frequency was found as follows: A/A 55.0%, A/G 33.6%, G/G 11.5%, where A is the wild allele (71.8%) and G is the mutated allele (28.2%). Our results are comparable to the NCBI SNP database for SNP A1450G. Patients were subdivided into subgroups containing the mutated allele: A/G+G/G (45.1%) and those homogenous for the wild allele: A/A (55.0%). All bleomycin treated patients (n=102) had more favorable lung function test result in the wild A/A genotype group, with significant difference in the forced vital capacity results (FVC), p=0.041. When narrowing patients to those who received only ABVD regimen (n=68), significantly more favorable results were seen in the wild A/A genotype group with every investigated test method (SGRQ score: p=0.035, lung scintigraphy results: p=0.045, spirometry results: FVC: p=0.020; forced expiratory volume in 1 s (FEV1): p=0.028). Univariate analysis also confirmed these results. As control group (n=29), patients treated with agents excluding bleomycin were tested with no significant differences between the A/G+G/G and A/A groups. Other factors (smoking, age, bleomycin dose, chest irradiation, kidney function, use of colony stimulating factors) that could potentially affect lung function were equally represented in all investigated subgroups.
Summary
BLMH gene polymorphism significantly distinguished in retrospective pulmonary test results of ABVD treated patients. Based on these results prospective trials could be designed to further evaluate its role in pulmonary toxicity of treating HL, and thus treatment could be adjusted individually. One of its potential roles could be to identify those cases even in the frontline setting, where brentuximab vedotin should be administered instead of bleomycin, either in the standard care or considering expense issues. Patients with multiple risk factors for lung toxicity should be particularly considered for this test method. Eventually, life expectancy and quality of life of HL patients wouldn’t remarkably differ from the untreated healthy population.
Session topic: Progess in Hodgkin lymphoma therapy: Incorporation of novel agents and reduction of side effects
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