title: Dose-Effect Relationship of Alkylating Agents on Testicular Function in Male Survivors of Childhood Lymphoma.
abstract: The purpose of our study was to assess the gonadal function in male survivors of childhood lymphoma. We studied 171 male survivors of childhood lymphoma (83 with B-cell non-Hodgkin lymphoma [B-NHL], 32 with T-cell non-Hodgkin lymphoma [T-NHL], 50 with Hodgkin lymphoma [HL], and 6 with anaplastic large-cell lymphoma [ALCL]), measuring follicle-stimulating hormone [FSH] and luteinizing hormone [LH] levels at a median age of 21.1 (17-30.4) years after a median delay of 9.3 (2-22.4) years from treatment. FSH levels were above normal range (≥10 IU/L) in 42.1% and LH levels ≥8 IU/L in only 8.9% of survivors. In multivariate analysis, only the following chemotherapeutic agents were associated with higher FSH or LH levels: cyclophosphamide (P < .0001, .04), lomustine (CCNU; P = .002, 0.04), and procarbazine (P < .0001, .07). No significant correlation was found between FSH or LH levels and age or pubertal status at diagnosis. Mean FSH level was significantly lower in NHL survivors treated more recently: 6 ± 5.1 IU/L in B-NHL survivors treated since 1986 versus 12.3 ± 5.4 IU/L for those treated before 1981 (P = .0001), and 6.8 ± 9.6 IU/L in T-NHL survivors treated since 1989 versus 9.4 ± 5.7 IU/L for those treated before 1989 (P = .035). In HL, mean FSH level was 12.4 ± 9.9 IU/L following procarbazine containing chemotherapy versus 3.4 ± 1.9 IU/L in the absence of procarbazine and increased significantly with the number of MOPP/OPPA (mechlorethamine, Oncovin [vincristine], procarbazine, and prednisone/Oncovin, procarbazine, and prednisone, and Adriamycin [doxorubicin]) courses received, from 6.8 ± 5.7 IU/L for 1-2 MOPP/OPPA to 12.6 ± 7.5 for 3-4 MOPP/OPPA and 19.6 ± 13.3 for more than 4 MOPP/OPPA (P for trend = .006). Testicular toxicity of alkylating agents on childhood lymphoma survivors is dose dependent and not correlated to diagnosis, age, or pubertal status at diagnosis.
authors.affiliation: a Department of Pediatric Oncology , Institut Gustave Roussy , Villejuif , France.
authors.forename: Marina
authors.initials: M
authors.lastname: Servitzoglou
authors.affiliation: b Radiation Epidemiology Group, Center for Research in Epidemiology and Population Health (CESP), Inserm U1018 , Université Paris-Sud XI , Villejuif , France.
authors.forename: Florent
authors.initials: F
authors.lastname: De Vathaire
authors.affiliation: a Department of Pediatric Oncology , Institut Gustave Roussy , Villejuif , France.
authors.forename: Odile
authors.initials: O
authors.lastname: Oberlin
authors.affiliation: a Department of Pediatric Oncology , Institut Gustave Roussy , Villejuif , France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Patte
authors.affiliation: b Radiation Epidemiology Group, Center for Research in Epidemiology and Population Health (CESP), Inserm U1018 , Université Paris-Sud XI , Villejuif , France.|c Department of Pediatric Endocrinology, APHP , Hôpitaux Paris-Sud , Site Bicetre , Le Kremlin-Bicetre , France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Thomas-Teinturier
mesh_terms: D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005640:Follicle Stimulating Hormone / Q000097:blood*; D005500:Follow-Up Studies; D006689:Hodgkin Disease / Q000097:blood / Q000188:drug therapy; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood*; D017728:Lymphoma, Large-Cell, Anaplastic / Q000097:blood / Q000188:drug therapy; D016399:Lymphoma, T-Cell / Q000097:blood / Q000188:drug therapy; D008297:Male; D017741:Survivors; D013737:Testis / Q000378:metabolism*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
keywords: alkylating agents; childhood lymphoma; fertility; testicular function