Summary
With the increasing cure rate of patients treated for Hodgkin's and non-Hodgkin's lymphoma, the evaluation of late effects on gonadal function remains an important issue. The gonadal function of relapse-free long-term survivors with high-grade non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) were studied; 24 of 119 patients with NHL treated between 1980 and 1990 and 66 of 364 patients with HD treated between 1975 and 1990 at Hannover University Medical School, who were younger than 45 years of age and in complete remission at the time of evaluation for at least 24 months after completion of therapy, were included into the analysis. Of 24 patients with NHL, 1/10 women (10%) and only 3/14 men (21%) showed signs of gonadal dysfunction. Three of these four patients had been treated with combined modality therapy followed by maintenance COP chemotherapy, resulting in high cumulative doses of cyclophosphamide (range: 12–43 g). In comparison, 13/26 (50%) women with HD suffered from premature ovarian failure, and 26/40 (65%) men showed signs of gonadal dysfunction with significant FSH elevations. No significant difference in the incidence of gonadal toxicity existed in patients treated with combined modality who received irradiation to either supra- or infradiaphragmatic radiation fields in combination with chemotherapy (70% versus 62%). A comparison of the chemotherapy regimens used in patients with NHL or HD shows that patients from both groups had received comparable median cumulative doses of cyclophosphamide, vincristine, and adriamycin, but only patients with HD had additionally received a median cumulative dose of 13.3 g of procarbazine per patient. A tendency towards a higher incidence of gonadal toxicity with higher cumulative doses of procarbazine received was found in patients with HD. The frequency of gonadal dysfunctions is markedly lower in patients treated for non-Hodgkin's lymphoma than in patients treated for Hodgkin's disease, approximately half of whom will be affected by long-term gonadal toxicity. Although the use of more intensive radiotherapy in patients with HD compared with NHL patients makes the evaluation of the influence of radiotherapy on gonadal toxicity more difficult, the current retrospective analysis raises the concern that, in addition to infradiaphragmatic radiotherapy, the use of procarbazine in regimens for the treatment of HD, like COPP or MOPP, may be a possible explanation for the differences in gonadal toxicity observed between patients with HD and those with NHL. Regimens including procarbazine should be avoided in patients wanting to preserve fertility since alternative chemotherapies with at least equal efficacy are available.
Similar content being viewed by others
References
Bonadonna G, Santoro A, Viviani S, Lombardi C, Ragni G (1984) Gonadal damage in Hodgkin's disease from cancer chemotherapeutic regimens. Arch Toxicol 7:140–145
Bonnadonna G, Valagussa P, Santoro A, Viviani S, Bonfante V, Banfi A (1989) Hodgkin's disease: the Milan cancer institute experience with MOPP and ABVD. Recent Results Cancer Res 117:167–74
Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES, Green MR, Gottlieb A, Peterson BA (1992) Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N. Engl J Med 327:1478–1484
Chapman RM, Sutcliffe SB, Malpas JS (1981) Male gonadal dysfunction in Hodgkin's disease: a prospective study. JAMA 245:1323–1328
Da Cunha MF, Meistrich ML, Fuller LM, Cundiff JH, Hagemeister FB, Velasquez WS, McLaughlin P, Riggs SA, Cabanillas FF, Salvador PG (1984) Recovery of spermatogenesis after treatment for Hodgkin's disease: limiting dose of MOPP chemotherapy. J Clin Oncol 2:571–577
De Kretser DM, Burger HG, Hudson B (1974) The relationship between germinal cells and serum FSH levels in males with infertility. J Clin Endocrinol Metab 38:787–793
Dumontet C, Bastion Y, Felman P, French M, Blanc M, Peaud PY, Coiffier B (1992) Long-term outcome and sequelae in aggressive lymphoma patients treated with the LNH-80 regimen. Ann Oncol 3:639–644
Horning SJ, Toppe RT, Kaplan HS, Rosenberg SA (1981) Female reproductive potential after treatment for Hodgkin's disease. N Engl J Med 304:1377–1382
Kader HA, Rostom AY (1991) Follicle-stimulating hormone levels as a predictor of recovery of spermatogenesis following cancer therapy. Clin Oncol (R Coll Radiol) 3:37–40
Kreuser ED, Felsenberg D, Behles C, Seibt-Jung H, Mielcarek M, Diehl V, Dahmen H, Thiel E (1992) Long-term gonadal dysfunction and its impact on bone mineralization in patients following COPP/ABVD chemotherapy for Hodgkin's disease. Ann Oncol 3 [Suppl 4]:105–110
Kreuser ED, Xiros N, Hetzel WD, Heimpel H (1987) Reproductive and endocrine gonadal capacity in patients treated with COPP chemotherapy for Hodgkin's disease. J Cancer Res Clin Oncol 113:260–266
Müller U, Stahel RA (1993) Gonadal function after MACOP-B or VACOP-B with or without dose intensification and ABMT in young patients with aggressive non-Hodgkin's lymphoma. Ann Oncol 4:399–402
Roeser HP, Stocks AE, Smith AJ (1978) Testicular damage due to cytotoxic drugs and recovery after cessation of therapy. Aust N Z Med 8:250–254
Schillsky RL, Sherins RJ, Hubbard SM, Wesley MN, Young RC, DeVita VT (1981) Long-term follow-up of ovarian function in women treated with MOPP chemotherapy for Hodgkin's disease. Am J Med 71:552–556
Urba WJ, Longo DL (1992) Hodgkin's disease. N Engl J Med 326:678–687
Waxman JH, Terry YA, Wrigley PF, Malpas JS, Ress LH, Besser GM, Lister TA (1982) Gonadal function in Hodgkin's disease: long-term follow-up of chemotherapy. Br J Med 285:1612–1613
Whitehead E, Shalet SM, Blackledge G, Crowther D, Beardwell CG (1983) The effect of combination chemotherapy on ovarian function in women treated for Hodgkin's disease. Cancer 52:988–993
Whitehead E, Shalet SM, Blackledge G, Crowther D, Beardwell CG (1982) The effect of Hodgkin's disease and combination chemotherapy and gonadal function in the adult male. Cancer 49:418–422
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bokemeyer, C., Schmoll, H.J., van Rhee, J. et al. Long-term gonadal toxicity after therapy for Hodgkin's and non-Hodgkin's lymphoma. Ann Hematol 68, 105–110 (1994). https://doi.org/10.1007/BF01727413
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01727413