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Sheri L Spunt - One of the best experts on this subject based on the ideXlab platform.
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cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer a report from the st jude lifetime cohort study
Lancet Oncology, 2014Co-Authors: Daniel M Green, Charles A Sklar, Wei Liu, William H Kutteh, Kyla Shelton, Wassim Chemaitilly, Chinghon Pui, James L Klosky, Sheri L SpuntAbstract:Summary Background Few data define the dose-specific relation between alkylating agent exposure and semen variables in adult survivors of childhood cancer. We undertook this study to test the hypothesis that increased exposure to alkylating agents would be associated with decreased sperm concentration in a cohort of adult male survivors of childhood cancer who were not exposed to radiation therapy for their childhood cancer. Methods We did semen analysis on 214 adult male survivors of childhood cancer (median age 7·7 years [range 0·01–20·3] at diagnosis, 29·0 years [18·4–56·1] at assessment, and a median of 21·0 years [10·5–41·6] since diagnosis) who had received alkylating agent chemotherapy but no radiation therapy. Alkylating agent exposure was estimated using the cyclophosphamide equivalent dose (CED). Odds ratios (ORs) and 95% CIs for Oligospermia (sperm concentration >0 and Findings Azoospermia was noted in 53 (25%) of 214 participants, Oligospermia in 59 (28%), and normospermia (sperm concentration ≥15 million per mL) in 102 (48%) participants. 31 (89%) of 35 participants who received CED less than 4000 mg/m 2 were normospermic. CED was negatively correlated with sperm concentration (correlation coefficient=–0·37, p 2 (SD 7274) in patients with azoospermia, 8480 mg/m 2 (4264) in patients with Oligospermia, and 6626 mg/m 2 (3576) in patients with normospermia. In multivariable analysis, CED was significantly associated with an increased risk per 1000 mg/m 2 CED for azoospermia (OR 1·22, 95% CI 1·11–1·34), and for Oligospermia (1·14, 1·04–1·25), but age at diagnosis and age at assessment were not. Interpretation Impaired spermatogenesis was unlikely when the CED was less than 4000 mg/m 2 . Although sperm concentration decreases with increasing CED, there was substantial overlap of CED associated with normospermia, Oligospermia, and azoospermia. These data can inform pretreatment patient counselling and use of fertility preservation services. Funding US National Cancer Institute, American Lebanese Syrian Associated Charities.
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alkylating agent exposure and sperm concentration in adult survivors of childhood cancer a report from the st jude lifetime sjlife cohort study
Journal of Clinical Oncology, 2014Co-Authors: Daniel M Green, Charles A Sklar, Wei Liu, William H Kutteh, Kyla Shelton, Wassim Chemaitilly, Chinghon Pui, James L Klosky, Sheri L Spunt, Monika L MetzgerAbstract:10010 Background: Male survivors of childhood cancer treated with alkylating agents (AA) are at risk for azoospermia; however, the long-term dose-risk relationship is unknown. Methods: Of the 287 SJLIFE participants treated with AA but no radiation therapy, 214 provided an evaluable semen sample (mean age at diagnosis: 7.9 years, mean age at evaluation: 29.8 years, and mean years from diagnosis to evaluation: 21.6 years). Survivors were categorized as azoospermia, Oligospermia (sperm concentration > 0 and < 15 million/ml), or normospermia (sperm concentration ≥ 15 million/ml). AA exposure was estimated using the cyclophosphamide equivalent dose (CED). Risks were estimated using the odds ratio (OR) and 95% confidence intervals (CI) from multinomial logistic regression analyses. Results: Among survivors 24.8% had azoospermia, 27.6% Oligospermia, and 47.6% normospermia (Table). CED was negatively correlated with sperm concentration (r = - 0.25, p< 0.001). Neither age at diagnosis nor age at evaluation was si...
Daniel M Green - One of the best experts on this subject based on the ideXlab platform.
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cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer a report from the st jude lifetime cohort study
Lancet Oncology, 2014Co-Authors: Daniel M Green, Charles A Sklar, Wei Liu, William H Kutteh, Kyla Shelton, Wassim Chemaitilly, Chinghon Pui, James L Klosky, Sheri L SpuntAbstract:Summary Background Few data define the dose-specific relation between alkylating agent exposure and semen variables in adult survivors of childhood cancer. We undertook this study to test the hypothesis that increased exposure to alkylating agents would be associated with decreased sperm concentration in a cohort of adult male survivors of childhood cancer who were not exposed to radiation therapy for their childhood cancer. Methods We did semen analysis on 214 adult male survivors of childhood cancer (median age 7·7 years [range 0·01–20·3] at diagnosis, 29·0 years [18·4–56·1] at assessment, and a median of 21·0 years [10·5–41·6] since diagnosis) who had received alkylating agent chemotherapy but no radiation therapy. Alkylating agent exposure was estimated using the cyclophosphamide equivalent dose (CED). Odds ratios (ORs) and 95% CIs for Oligospermia (sperm concentration >0 and Findings Azoospermia was noted in 53 (25%) of 214 participants, Oligospermia in 59 (28%), and normospermia (sperm concentration ≥15 million per mL) in 102 (48%) participants. 31 (89%) of 35 participants who received CED less than 4000 mg/m 2 were normospermic. CED was negatively correlated with sperm concentration (correlation coefficient=–0·37, p 2 (SD 7274) in patients with azoospermia, 8480 mg/m 2 (4264) in patients with Oligospermia, and 6626 mg/m 2 (3576) in patients with normospermia. In multivariable analysis, CED was significantly associated with an increased risk per 1000 mg/m 2 CED for azoospermia (OR 1·22, 95% CI 1·11–1·34), and for Oligospermia (1·14, 1·04–1·25), but age at diagnosis and age at assessment were not. Interpretation Impaired spermatogenesis was unlikely when the CED was less than 4000 mg/m 2 . Although sperm concentration decreases with increasing CED, there was substantial overlap of CED associated with normospermia, Oligospermia, and azoospermia. These data can inform pretreatment patient counselling and use of fertility preservation services. Funding US National Cancer Institute, American Lebanese Syrian Associated Charities.
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alkylating agent exposure and sperm concentration in adult survivors of childhood cancer a report from the st jude lifetime sjlife cohort study
Journal of Clinical Oncology, 2014Co-Authors: Daniel M Green, Charles A Sklar, Wei Liu, William H Kutteh, Kyla Shelton, Wassim Chemaitilly, Chinghon Pui, James L Klosky, Sheri L Spunt, Monika L MetzgerAbstract:10010 Background: Male survivors of childhood cancer treated with alkylating agents (AA) are at risk for azoospermia; however, the long-term dose-risk relationship is unknown. Methods: Of the 287 SJLIFE participants treated with AA but no radiation therapy, 214 provided an evaluable semen sample (mean age at diagnosis: 7.9 years, mean age at evaluation: 29.8 years, and mean years from diagnosis to evaluation: 21.6 years). Survivors were categorized as azoospermia, Oligospermia (sperm concentration > 0 and < 15 million/ml), or normospermia (sperm concentration ≥ 15 million/ml). AA exposure was estimated using the cyclophosphamide equivalent dose (CED). Risks were estimated using the odds ratio (OR) and 95% confidence intervals (CI) from multinomial logistic regression analyses. Results: Among survivors 24.8% had azoospermia, 27.6% Oligospermia, and 47.6% normospermia (Table). CED was negatively correlated with sperm concentration (r = - 0.25, p< 0.001). Neither age at diagnosis nor age at evaluation was si...
Yingxia Cui - One of the best experts on this subject based on the ideXlab platform.
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ab188 meiotic prophase i defects in an oligospermic man with wolf hirschhorn syndrome with ring chromosome 4
Translational Andrology and Urology, 2014Co-Authors: Qi Yao, Bing Yao, Xin-yi Xia, Liu Wang, Qinghua Shi, Hongliu Gao, Yingxia CuiAbstract:Background Ring chromosomes are often associated with spermatogenetic failure. However, the mechanism is poorly understood. We here reported a single man with severe Oligospermia and a ring chromosome 4 with a microdeletion at 4p16.3.
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meiotic prophase i defects in an oligospermic man with wolf hirschhorn syndrome with ring chromosome 4
Molecular Cytogenetics, 2014Co-Authors: Qi Yao, Bing Yao, Xin-yi Xia, Liu Wang, Qinghua Shi, Hongliu Gao, Yingxia CuiAbstract:Background: Ring chromosomes are often associated with spermatogenetic failure. However, the mechanism is poorly understood. We here reported a single man with severe Oligospermia and a ring chromosome 4 with a microdeletion at 4p16.3. Results: Synapsis (as SCP3), recombination (as MLH1) and transcriptional inactivation (as BRCA1) in a testicular biopsy were examined by fluorescence immunostaining. In the Oligospermia patient, 35.4% of spermatocytes were in zygotene phase compared with 5.2% in controls. The patient had a significantly reduced recombination frequency with mean of 45.9 MLH1 foci/cell compared with 47.8 in controls. In the patient, chromosome 4 in all pachytene cells displayed loop formation with varying degrees of unpaired regions. BRCA1 localized along asynapsed regions regardless of XY body association. Conclusions: Ring chromosome 4 might affect the progression of meiosis I prophase, synapse formation, and transcriptional activation of asynapsed areas, and impair male fertility.
William H Kutteh - One of the best experts on this subject based on the ideXlab platform.
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cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer a report from the st jude lifetime cohort study
Lancet Oncology, 2014Co-Authors: Daniel M Green, Charles A Sklar, Wei Liu, William H Kutteh, Kyla Shelton, Wassim Chemaitilly, Chinghon Pui, James L Klosky, Sheri L SpuntAbstract:Summary Background Few data define the dose-specific relation between alkylating agent exposure and semen variables in adult survivors of childhood cancer. We undertook this study to test the hypothesis that increased exposure to alkylating agents would be associated with decreased sperm concentration in a cohort of adult male survivors of childhood cancer who were not exposed to radiation therapy for their childhood cancer. Methods We did semen analysis on 214 adult male survivors of childhood cancer (median age 7·7 years [range 0·01–20·3] at diagnosis, 29·0 years [18·4–56·1] at assessment, and a median of 21·0 years [10·5–41·6] since diagnosis) who had received alkylating agent chemotherapy but no radiation therapy. Alkylating agent exposure was estimated using the cyclophosphamide equivalent dose (CED). Odds ratios (ORs) and 95% CIs for Oligospermia (sperm concentration >0 and Findings Azoospermia was noted in 53 (25%) of 214 participants, Oligospermia in 59 (28%), and normospermia (sperm concentration ≥15 million per mL) in 102 (48%) participants. 31 (89%) of 35 participants who received CED less than 4000 mg/m 2 were normospermic. CED was negatively correlated with sperm concentration (correlation coefficient=–0·37, p 2 (SD 7274) in patients with azoospermia, 8480 mg/m 2 (4264) in patients with Oligospermia, and 6626 mg/m 2 (3576) in patients with normospermia. In multivariable analysis, CED was significantly associated with an increased risk per 1000 mg/m 2 CED for azoospermia (OR 1·22, 95% CI 1·11–1·34), and for Oligospermia (1·14, 1·04–1·25), but age at diagnosis and age at assessment were not. Interpretation Impaired spermatogenesis was unlikely when the CED was less than 4000 mg/m 2 . Although sperm concentration decreases with increasing CED, there was substantial overlap of CED associated with normospermia, Oligospermia, and azoospermia. These data can inform pretreatment patient counselling and use of fertility preservation services. Funding US National Cancer Institute, American Lebanese Syrian Associated Charities.
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alkylating agent exposure and sperm concentration in adult survivors of childhood cancer a report from the st jude lifetime sjlife cohort study
Journal of Clinical Oncology, 2014Co-Authors: Daniel M Green, Charles A Sklar, Wei Liu, William H Kutteh, Kyla Shelton, Wassim Chemaitilly, Chinghon Pui, James L Klosky, Sheri L Spunt, Monika L MetzgerAbstract:10010 Background: Male survivors of childhood cancer treated with alkylating agents (AA) are at risk for azoospermia; however, the long-term dose-risk relationship is unknown. Methods: Of the 287 SJLIFE participants treated with AA but no radiation therapy, 214 provided an evaluable semen sample (mean age at diagnosis: 7.9 years, mean age at evaluation: 29.8 years, and mean years from diagnosis to evaluation: 21.6 years). Survivors were categorized as azoospermia, Oligospermia (sperm concentration > 0 and < 15 million/ml), or normospermia (sperm concentration ≥ 15 million/ml). AA exposure was estimated using the cyclophosphamide equivalent dose (CED). Risks were estimated using the odds ratio (OR) and 95% confidence intervals (CI) from multinomial logistic regression analyses. Results: Among survivors 24.8% had azoospermia, 27.6% Oligospermia, and 47.6% normospermia (Table). CED was negatively correlated with sperm concentration (r = - 0.25, p< 0.001). Neither age at diagnosis nor age at evaluation was si...
Wassim Chemaitilly - One of the best experts on this subject based on the ideXlab platform.
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cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer a report from the st jude lifetime cohort study
Lancet Oncology, 2014Co-Authors: Daniel M Green, Charles A Sklar, Wei Liu, William H Kutteh, Kyla Shelton, Wassim Chemaitilly, Chinghon Pui, James L Klosky, Sheri L SpuntAbstract:Summary Background Few data define the dose-specific relation between alkylating agent exposure and semen variables in adult survivors of childhood cancer. We undertook this study to test the hypothesis that increased exposure to alkylating agents would be associated with decreased sperm concentration in a cohort of adult male survivors of childhood cancer who were not exposed to radiation therapy for their childhood cancer. Methods We did semen analysis on 214 adult male survivors of childhood cancer (median age 7·7 years [range 0·01–20·3] at diagnosis, 29·0 years [18·4–56·1] at assessment, and a median of 21·0 years [10·5–41·6] since diagnosis) who had received alkylating agent chemotherapy but no radiation therapy. Alkylating agent exposure was estimated using the cyclophosphamide equivalent dose (CED). Odds ratios (ORs) and 95% CIs for Oligospermia (sperm concentration >0 and Findings Azoospermia was noted in 53 (25%) of 214 participants, Oligospermia in 59 (28%), and normospermia (sperm concentration ≥15 million per mL) in 102 (48%) participants. 31 (89%) of 35 participants who received CED less than 4000 mg/m 2 were normospermic. CED was negatively correlated with sperm concentration (correlation coefficient=–0·37, p 2 (SD 7274) in patients with azoospermia, 8480 mg/m 2 (4264) in patients with Oligospermia, and 6626 mg/m 2 (3576) in patients with normospermia. In multivariable analysis, CED was significantly associated with an increased risk per 1000 mg/m 2 CED for azoospermia (OR 1·22, 95% CI 1·11–1·34), and for Oligospermia (1·14, 1·04–1·25), but age at diagnosis and age at assessment were not. Interpretation Impaired spermatogenesis was unlikely when the CED was less than 4000 mg/m 2 . Although sperm concentration decreases with increasing CED, there was substantial overlap of CED associated with normospermia, Oligospermia, and azoospermia. These data can inform pretreatment patient counselling and use of fertility preservation services. Funding US National Cancer Institute, American Lebanese Syrian Associated Charities.
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alkylating agent exposure and sperm concentration in adult survivors of childhood cancer a report from the st jude lifetime sjlife cohort study
Journal of Clinical Oncology, 2014Co-Authors: Daniel M Green, Charles A Sklar, Wei Liu, William H Kutteh, Kyla Shelton, Wassim Chemaitilly, Chinghon Pui, James L Klosky, Sheri L Spunt, Monika L MetzgerAbstract:10010 Background: Male survivors of childhood cancer treated with alkylating agents (AA) are at risk for azoospermia; however, the long-term dose-risk relationship is unknown. Methods: Of the 287 SJLIFE participants treated with AA but no radiation therapy, 214 provided an evaluable semen sample (mean age at diagnosis: 7.9 years, mean age at evaluation: 29.8 years, and mean years from diagnosis to evaluation: 21.6 years). Survivors were categorized as azoospermia, Oligospermia (sperm concentration > 0 and < 15 million/ml), or normospermia (sperm concentration ≥ 15 million/ml). AA exposure was estimated using the cyclophosphamide equivalent dose (CED). Risks were estimated using the odds ratio (OR) and 95% confidence intervals (CI) from multinomial logistic regression analyses. Results: Among survivors 24.8% had azoospermia, 27.6% Oligospermia, and 47.6% normospermia (Table). CED was negatively correlated with sperm concentration (r = - 0.25, p< 0.001). Neither age at diagnosis nor age at evaluation was si...
