EHA Library - The official digital education library of European Hematology Association (EHA)

CHILDBEARING AMONG CLASSICAL HODGKIN LYMPHOMA SURVIVORS TREATED WITH BEACOPP AND ABVD IN SWEDEN, DENMARK, AND NORWAY
Author(s): ,
Joshua P Entrop
Affiliations:
Clinical Epidemiology Division, Department of Medicine Solna,Karolinska Institutet,Stockholm,Suède;Clinical Epidemiology Division, Department of Medicine Solna,Karolinska Institutet,Stockholm,Schweden;Clinical Epidemiology Division, Department of Medicine Solna,Karolinska Institutet,Stockholm,Svezia;Clinical Epidemiology Division, Department of Medicine Solna,Karolinska Institutet,Stockholm,Sweden
,
Caroline E Weibull
Affiliations:
Clinical Epidemiology Division, Department of Medicine Solna,Karolinska Institutet,Stockholm,Suède;Clinical Epidemiology Division, Department of Medicine Solna,Karolinska Institutet,Stockholm,Schweden;Clinical Epidemiology Division, Department of Medicine Solna,Karolinska Institutet,Stockholm,Svezia;Clinical Epidemiology Division, Department of Medicine Solna,Karolinska Institutet,Stockholm,Sweden
,
Karin E Smedby
Affiliations:
Clinical Epidemiology Division, Department of Medicine Solna,Karolinska Institutet,Stockholm,Suède;Clinical Epidemiology Division, Department of Medicine Solna,Karolinska Institutet,Stockholm,Schweden;Clinical Epidemiology Division, Department of Medicine Solna,Karolinska Institutet,Stockholm,Svezia;Clinical Epidemiology Division, Department of Medicine Solna,Karolinska Institutet,Stockholm,Sweden
,
Lasse H Jakobsen
Affiliations:
Department of Hematology, Clinical Cancer Research Center,Aalborg University Hospital,Aalborg,Danemark;Department of Hematology, Clinical Cancer Research Center,Aalborg University Hospital,Aalborg,Dänemark;Department of Hematology, Clinical Cancer Research Center,Aalborg University Hospital,Aalborg,Danimarca;Department of Hematology, Clinical Cancer Research Center,Aalborg University Hospital,Aalb
,
Andreas K Øvlisen
Affiliations:
Department of Hematology, Clinical Cancer Research Center,Aalborg University Hospital,Aalborg,Danemark;Department of Hematology, Clinical Cancer Research Center,Aalborg University Hospital,Aalborg,Dänemark;Department of Hematology, Clinical Cancer Research Center,Aalborg University Hospital,Aalborg,Danimarca;Department of Hematology, Clinical Cancer Research Center,Aalborg University Hospital,Aalb
,
Daniel Molin
Affiliations:
Department of Immunology, Genetics and Pathology, Unit of Experimental and Clinical Oncology,Uppsala University,Uppsala,Suède;Department of Immunology, Genetics and Pathology, Unit of Experimental and Clinical Oncology,Uppsala University,Uppsala,Schweden;Department of Immunology, Genetics and Pathology, Unit of Experimental and Clinical Oncology,Uppsala University,Uppsala,Svezia;Department of Immu
,
Ingrid Glimelius
Affiliations:
Department of Immunology, Genetics and Pathology, Unit of Experimental and Clinical Oncology,Uppsala University,Uppsala,Suède;Department of Immunology, Genetics and Pathology, Unit of Experimental and Clinical Oncology,Uppsala University,Uppsala,Schweden;Department of Immunology, Genetics and Pathology, Unit of Experimental and Clinical Oncology,Uppsala University,Uppsala,Svezia;Department of Immu
,
Anja Marklund
Affiliations:
Department of Reproductive Medicine, Division of Gynecology and Reproduction,Karolinska University Hospital,Stockholm,Suède;Department of Reproductive Medicine, Division of Gynecology and Reproduction,Karolinska University Hospital,Stockholm,Schweden;Department of Reproductive Medicine, Division of Gynecology and Reproduction,Karolinska University Hospital,Stockholm,Svezia;Department of Reproducti
,
Knut B Smeland
Affiliations:
Department of Oncology,Oslo University Hospital,Oslo,Norvège;Department of Oncology,Oslo University Hospital,Oslo,Norwegen;Department of Oncology,Oslo University Hospital,Oslo,Norvegia;Department of Oncology,Oslo University Hospital,Oslo,Norway;Department of Oncology,Oslo University Hospital,Oslo,Noruega;Department of Oncology,Oslo University Hospital,Oslo,Noorwegen;Department of Oncology,Oslo Uni
,
Tarec C El-Galaly
Affiliations:
Department of Hematology, Clinical Cancer Research Center,Aalborg University Hospital,Aalborg,Danemark;Department of Hematology, Clinical Cancer Research Center,Aalborg University Hospital,Aalborg,Dänemark;Department of Hematology, Clinical Cancer Research Center,Aalborg University Hospital,Aalborg,Danimarca;Department of Hematology, Clinical Cancer Research Center,Aalborg University Hospital,Aalb
Sandra Eloranta
Affiliations:
Clinical Epidemiology Division, Department of Medicine Solna,Karolinska Institutet,Stockholm,Suède;Clinical Epidemiology Division, Department of Medicine Solna,Karolinska Institutet,Stockholm,Schweden;Clinical Epidemiology Division, Department of Medicine Solna,Karolinska Institutet,Stockholm,Svezia;Clinical Epidemiology Division, Department of Medicine Solna,Karolinska Institutet,Stockholm,Sweden
(Abstract release date: 05/12/22) EHA Library. Philipp Entrop J. 06/10/22; 357066; S202
Joshua Philipp Entrop
Joshua Philipp Entrop
Contributions
Abstract
Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S202

Type: Oral Presentation

Session title: Hodgkin lymphoma - Clinical

Background

Recent studies have shown decreased childbearing rates in some classical Hodgkin lymphoma (cHL) survivors compared to the general population. This decrease is hypothesized to be caused by administered intensive chemotherapy. Understanding if currently used treatment protocols lead to reduced post-treatment childbirth potential is important as differential impact on childbearing may influence treatment decisions for younger patients. Firm conclusions from previous population-based studies have been hampered by low power for specific treatment contrasts.

Aims

To increase understanding of differences in childbearing patterns among male and female HL survivors treated with ABVD and BEACOPP in a study combining population-based register data from Sweden, Denmark, and Norway.

Methods
In this cohort study 2,937 individuals aged 18-40 years with a recorded diagnosis of cHL in the Swedish lymphoma register (SLR), the Danish lymphoma registry (LYFO), or the clinical database at Oslo University Hospital (OUH) between 1995 and 2019 were included. Information on first-line chemotherapy treatment was available in the registers. Treatment regimens were classified as ABVD, 6-8 BEACOPP, or other. The SLR, LYFO, and OUH databases were linked to national medical birth registers to obtain information on childbirths. Follow-up started 9 months after cHL diagnosis and was accrued until date of first childbirth, death, or administrative censoring (December 2017, 2018, or 2019 for Norway, Sweden, and Denmark, respectively) or after 10 years. Females were additionally censored at date of relapse or stem cell transplantation due to the limited accessibility of assisted reproductive techniques for female patients experiencing one of those events. Stratified Cox models allowing for effect modification between sex and treatment and adjusted for stage, age at diagnosis, year of diagnosis, parity, and performance status were used to estimate hazard ratios (HRs). Flexible parametric survival models were used to estimate marginal childbirth rates and standardized cumulative incidence of childbirth across treatment groups. A comprehensive study analysis plan been published and pre-registered on the Open Science Framework (https://osf.io/eumy5/).

Results
In summary, 75% of HL patients were treated with ABVD and 10.8% with 6-8 BEACOPP. An additional 14.2% received other treatments or had missing treatment information and were excluded from further analyses. The rate of first childbirth per 1,000 person-years for males and females was 45.5 and 50.0 respectively in the ABVD group, and 23.8 and 43.5 in the 6-8 BEACOPP group. The adjusted HR of first childbirths for males and females, comparing patients treated with 6-8 BEACOPP to ABVD were 0.54 (95% CI 0.37-0.79) and 0.92 (95% CI 0.61-1.39) respectively. Plots of the cause-specific cumulative incidence functions (CIF) of childbirth show a constantly lower proportion of male patients with childbirths over time since HL diagnosis comparing patients treated with 6-8 BEACOPP and ABVD. However, this difference was not present among female patients. Adjusted marginal estimates of the cause-specific CIF of childbirth showed the same pattern.

Conclusion
BEACOPP treatment is associated with decreased childbearing rates in male but not female HL patients. Infertility counselling for this group is advisable.

Keyword(s): Chemotherapy toxicity, Fertility, Hodgkin's lymphoma

Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S202

Type: Oral Presentation

Session title: Hodgkin lymphoma - Clinical

Background

Recent studies have shown decreased childbearing rates in some classical Hodgkin lymphoma (cHL) survivors compared to the general population. This decrease is hypothesized to be caused by administered intensive chemotherapy. Understanding if currently used treatment protocols lead to reduced post-treatment childbirth potential is important as differential impact on childbearing may influence treatment decisions for younger patients. Firm conclusions from previous population-based studies have been hampered by low power for specific treatment contrasts.

Aims

To increase understanding of differences in childbearing patterns among male and female HL survivors treated with ABVD and BEACOPP in a study combining population-based register data from Sweden, Denmark, and Norway.

Methods
In this cohort study 2,937 individuals aged 18-40 years with a recorded diagnosis of cHL in the Swedish lymphoma register (SLR), the Danish lymphoma registry (LYFO), or the clinical database at Oslo University Hospital (OUH) between 1995 and 2019 were included. Information on first-line chemotherapy treatment was available in the registers. Treatment regimens were classified as ABVD, 6-8 BEACOPP, or other. The SLR, LYFO, and OUH databases were linked to national medical birth registers to obtain information on childbirths. Follow-up started 9 months after cHL diagnosis and was accrued until date of first childbirth, death, or administrative censoring (December 2017, 2018, or 2019 for Norway, Sweden, and Denmark, respectively) or after 10 years. Females were additionally censored at date of relapse or stem cell transplantation due to the limited accessibility of assisted reproductive techniques for female patients experiencing one of those events. Stratified Cox models allowing for effect modification between sex and treatment and adjusted for stage, age at diagnosis, year of diagnosis, parity, and performance status were used to estimate hazard ratios (HRs). Flexible parametric survival models were used to estimate marginal childbirth rates and standardized cumulative incidence of childbirth across treatment groups. A comprehensive study analysis plan been published and pre-registered on the Open Science Framework (https://osf.io/eumy5/).

Results
In summary, 75% of HL patients were treated with ABVD and 10.8% with 6-8 BEACOPP. An additional 14.2% received other treatments or had missing treatment information and were excluded from further analyses. The rate of first childbirth per 1,000 person-years for males and females was 45.5 and 50.0 respectively in the ABVD group, and 23.8 and 43.5 in the 6-8 BEACOPP group. The adjusted HR of first childbirths for males and females, comparing patients treated with 6-8 BEACOPP to ABVD were 0.54 (95% CI 0.37-0.79) and 0.92 (95% CI 0.61-1.39) respectively. Plots of the cause-specific cumulative incidence functions (CIF) of childbirth show a constantly lower proportion of male patients with childbirths over time since HL diagnosis comparing patients treated with 6-8 BEACOPP and ABVD. However, this difference was not present among female patients. Adjusted marginal estimates of the cause-specific CIF of childbirth showed the same pattern.

Conclusion
BEACOPP treatment is associated with decreased childbearing rates in male but not female HL patients. Infertility counselling for this group is advisable.

Keyword(s): Chemotherapy toxicity, Fertility, Hodgkin's lymphoma

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