Originally published as JCO Early Release 10.1200/JCO.2006.10.2020 on May 21 2007

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Gonadal Function in Males After Chemotherapy for Early-Stage Hodgkin's Lymphoma Treated in Four Subsequent Trials by the European Organisation for Research and Treatment of Cancer: EORTC Lymphoma Group and the Groupe d'Étude des Lymphomes de l'Adulte

Marleen A.E. van der Kaaij, Natacha Heutte, Nolwenn Le Stang, John M.M. Raemaekers, Arnold H.M. Simons, Patrice Carde, Evert M. Noordijk, Christophe Fermé, José Thomas, Houchingue Eghbali, Hanneke C. Kluin-Nelemans, Michel Henry-Amar

From the Departments of Hematology and Gynecology, University Medical Centre Groningen, University of Groningen, Groningen; Department of Hematology, University Medical Centre Nijmegen, Nijmegen; Department of Radiotherapy, Leiden University Medical Centre, Leiden, the Netherlands; the Clinical Research Unit; Groupe Régional d'Etudes sur le Cancer (GRECAN 1772), University of Caen Basse-Normandie, Centre François Baclesse, Caen; Department of Hematology, Institut Bergonié, Bordeaux; the Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France; and the Department of Oncology, UZ Gasthuisberg, Leuven, Belgium

Address reprint requests to Hanneke C. Kluin-Nelemans, MD, PhD, Department of Hematology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9700 RB, PO Box 30.001, Groningen, the Netherlands; e-mail: j.c.kluin{at}int.umcg.nl

Purpose To analyze fertility in male patients treated with various combinations of radiotherapy and chemotherapy, with or without alkylating agents, or with radiotherapy alone for Hodgkin's lymphoma.

Patients and Methods Follicle-stimulating hormone (FSH) levels were measured in patients with early-stage upper-diaphragmatic disease enrolled in four European Organisation for Research and Treatment of Cancer (EORTC) trials (H6-H9). Median follow-up after therapy was 32 months. Patients with FSH measurement at least 12 months after end of treatment (n = 355) were selected to assess post-treatment fertility. Patients with FSH measurement 0 to 9 months after therapy (n = 349) were selected to analyze fertility recovery; of these, patients with elevated FSH (> 10 U/L; n = 101) were followed until recovery. Factors predictive for therapy-related infertility were assessed by logistic regression.

Results The proportion of elevated FSH was 3% and 8% in patients treated with radiotherapy only or with nonalkylating chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine [ABVD], epirubicin, bleomycin, vinblastine, prednisone [EBVP]); it was 60% (P < .001) after chemotherapy containing alkylating agents (mechlorethamine, vincristine, procarbazine, prednisone [MOPP], MOPP/doxorubicin, bleomycin, vinblastine [ABV], bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone [BEACOPP]). After a median time of 19 months, recovery of fertility occurred in 82% of patients treated without alkylating chemotherapy. This proportion was 30%, statistically (P < .001) lower in those treated with alkylating chemotherapy, and median time to recovery was 27 months. The post-treatment proportion of elevated FSH increased significantly (P < .001) with the dose of alkylating chemotherapy administered, and recovery was less frequent and slower after higher doses. Age more than 50 years and stage II disease also contributed to poor outcome.

Conclusion Fertility can be secured after nonalkylating chemotherapy for Hodgkin's lymphoma. In contrast, alkylating chemotherapy has a dismal effect, even after a limited number of cycles.

published online ahead of print at www.jco.org on May 21, 2007.

Supported by research grants from the Lance Armstrong Foundation.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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