Oncofertility in men cured of Hodgkin’s lymphoma as a child
https://doi.org/10.21518/2079-701X-2019-10-164-171
Abstract
Hodgkin’s lymphoma, being a highly malignant disease, has now acquired the property of a curative one. The article describes the basic principles of therapy of children with Hodgkin’s lymphoma, slow fixation of risk-adapted treatment positions. The possibility of complete cure of most patients appeared, which made this tumor a unique model for studying the remote consequences of cancer treatment. After the antitumor treatment of Hodgkin’s lymphoma, boys may suffer from testicular insufficiency (due to cytostatics), obstructive azoospermia (as a consequence of radiation therapy in the pelvic area), hypogonadism (secondary - after exposure of the pituitary gland to radiation, primary - after exposure of the pelvis due to the toxic effects of cytostatics). In order to reduce the gonadotoxicity of treatment, studies are being conducted to modify chemotherapy in the direction of lowering the doses of alkylating cytostatics, reducing the doses of radiation therapy without losing the effectiveness of treatment. Regardless of the cause of male infertility diagnosis includes the collection of reproductive history, external examination of the genitals, analysis of ejaculate, ultrasound examination of the scrotum, assessment of hormone levels (follicle stimulating hormone, total testosterone, serum testosterone, luteinizing hormone, prolactin, inhibin B, thyroid stimulating hormone).
About the Authors
S. A. KulevaRussian Federation
Dr. of Sci. (Med.), Head of the Department of Chemotherapy and Combined Treatment of Malignant Tumors in Children, Leading Researcher of the Scientific Department of Innovative Methods of Therapeutic Oncology and Rehabilitation, Professor of the Educational and Methodological Department of the Federal State Budgetary Institution «National Medical Research Center of Oncology named after N.N. Petrov» of the Ministry of Health of the Russian Federation.
D. N. Kurochkina
Russian Federation
Oncologist of the day hospital of the State Budgetary Healthcare Institution «St. Petersburg Clinical Scientific and Practical Center of Specialized Medical Care (Oncological)».
D. A. Zvyagintseva
Russian Federation
Cand. of Sci. (Med.), doctor - children’s oncologist of the department of chemotherapy and combined treatment of malignant tumors in children of the Federal State Budgetary Institution «National Medical Research
Center of Oncology named after N.N. Petrov» of the Ministry of Health of the Russian Federation.
S. V. Ivanova
Russian Federation
Cand. of Sci. (Med.), doctor - pediatric oncologist of the department of chemotherapy and combined treatment of malignant tumors in children of the Federal State Budget Institution «National Medical Research Center of Oncology named after N.N. Petrov» of the Ministry of Health of the Russian Federation.
Ye. V. Tsyrlina
Russian Federation
Cand. of Sci. (Med.), Leading Researcher of the Oncoendocrinology Research Laboratory of the Federal State Budgetary Institution «National Medical Research Center of Oncology named after N.N. Petrov» of the Ministry of Health of the Russian Federation.
References
1. Мерабишвили В.М. Выживаемость онкологических больных. СПб.: Коста, 2006. 440 с. [Merabishvili V.M. Survival rate of oncological patients. St. Petersburg: Costa, 2006. 440 p.] (In Russ.)
2. Мень Т.Х., Поляков В.Г., Алиев М.Д. Эпидемиология злокачественных новообразований у детей в России. Онкопедиатрия. 2014;1:7-12. [Men’ T.H., Polyakov V.G., Aliev M.D. Epidemiology of malignant neoplasms in children in Russia. Onkopediatriya. 2014;1:7-12.] (In Russ.)
3. Ларина Ю.В., Миненко С.В., Биячуев Э.Р., Пшонкин А.В., Хуажева Н.К., Птушкин В.В. Лечение распространенных форм лимфомы Ходжкина у подростков и молодых взрослых. Проблема эффективности и токсичности. Онкогематология. 2014;1:11-18. [Larina Yu.V., Minenko S.V., Biyachuev E.R., Pshonkin A.V., Khuazheva N.K., Ptushkin V.V. Treatment of common forms of Hodgkin lymphoma in adolescents and young adults. Problem of efficacy and toxicity. Onkogematologiya. 2014;1:11-18.] (In Russ.)
4. Демина Е.А. Лимфома Ходжкина. Возможности современной терапии первичных больных. РМЖ. 2004;19:1113. [Demina E.A. Hodgkin’s lymphoma. Possibilities of modern therapy of primary patients. RMZh. 2004;19:1113.] (In Russ.)
5. Кулева С.А., Колыгин Б.А. Отдаленные последствия противоопухолевой терапии у детей. Вопр. oнкол. 2012;4:454-463. [Kuleva S.A., Kolygin B.A. Remote consequences of antitumor therapy in children. Vopr. onkol. 2012;4:454-463.] (In Russ.)
6. Колыгин Б.А., Кулева С.А. Последствия противоопухолевой терапии у детей. СПб., 2011. 184 с. [Kolygin B.A., Kuleva S.A. Consequences of antitumor therapy in children. St. Petersburg, 2011. 184 p.] (In Russ.)
7. Демина Е.А. Лимфома Ходжкина: от Томаса Ходжкина до наших дней. Клин. oнкогематол., 2008;2:114-118. [Demina E.A. Hodgkin’s lymphoma: from Thomas Hodgkin to the present day. Klin. onkogematol., 2008;2:114-118.] (In Russ.)
8. Pusey W.A. Cases of sarcoma and of Hodgkin’s disease treated by exposures to X-rays: a preliminary report. JAMA. 1902;38:166-169.
9. Peters V. A study of survival in Hodgkin’s disease treated by irradiation. Am. J. Roent. 1950;63:299-311.
10. De Vita V. Combination chemotherapy in the treatment of advanced Hodgkin’s disease. Ann. Intern. Med. 1970;73:881-895.
11. Bonadonna G. Combination chemotherapy of Hodgkin’s disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP. Cancer. 1975;36:252-259.
12. Prosnitz L.R. Consolidation radiotherapy in the treatment of advanced Hodgkin’s disease: is it dead? Int. J. Radiat. Oncol. Biol. Phys. 2003;56:605-608.
13. Винокуров А.А., Варфоломеева С.Р., Тарусин Д.И. Гонадотоксичность терапии лимфомы Ходжкина у подростков и молодых мужчин: актуальность проблемы и пути решения (обзор литературы). Онкогематология. 2011;2:12-19. [Vinokurov A.A., Varfolomeeva S.R., Tarusin D.I. Gonadotoxicity of Hodgkin’s lymphoma therapy in teenagers and young men: relevance of the problem and solutions (literature review). Onkogematologiya. 2011;2:12-19.] (In Russ.)
14. Кулева С.А., Анишкин М.Ю., Колыгин Б.А. Сравнительный анализ двух риск-адаптированных программ, используемых в терапии лимфомы Ходжкина у детей и подростков. Вопр. oнкол. 2008;1:53-58. [Kuleva S.A., Anishkin M.Yu., Kolygin B.A. Comparative analysis of two risk-adapted programs used in therapy of Hodgkin’s lymphoma in children and adolescents. Vopr. onkol. 2008;1:53-58.] (In Russ.)
15. Ansell S.M. Hodgkin lymphoma: 2016 update on diagnosis, risk-stratification, and management. Am. J. Hematol. 2016;91(4):434-442.
16. Smith R.S. Prognostic factors for children with Hodgkin’s disease treated with combinedmodality therapy. J. Clin. Oncol. 2003;21(10):2026-2033.
17. Weiner M.A. Intensive chemotherapy and lowdose radiotherapy for the treatment of advanced-stage Hodgkin’s disease in pediatric patients: a Pediatric Oncology Group Study. J. Clin. Oncol. 1991;9(9):1591-1598.
18. Vecchi V. Treatment of pediatric Hodgkin’s disease tailored to stage, mediastinal mass, and age. An Italian (AIEOP) multicenter study on 215 patients. Cancer. 1993;72(6):2049-2057.
19. Schellong G. High cure rates and reduced longterm toxicity in pediatric Hodgkin’s disease: the German-Austrian Multicenter Trial DAL-HD-90. J. Clin. Oncol. 1999;17(12):3736-3744.
20. Tebbi C.K., Mendenhall N., London W.B., Williams J.L., de Alarcon P.A., Chauvenet A.R. Treatment of stage I, IIA, IIIA1 pediatric Hodgkin disease with doxorubicin, bleomycin, vincristine and etoposide (DBVE) and radiation: a Pediatric Oncology Group (POG) study. Pediatr. Blood Cancer. 2006;46(2):198-202.
21. Kelly K.M., Sposto R., Hutchinson R., Massey V., McCarten K., Perkins S. et al. BEACOPP chemotherapy is a highly effective regimen in children and adolescents with high-risk Hodgkin lymphoma: a report from the Children’s Oncology Group. Blood. 2011;117(9):2596-2603.
22. Tebbi C.K., Mendenhall N.P., London W.B., Williams J.L., Hutchison R.E., Fitzgerald T.J. et al. Response-dependent and reduced treatment in lower risk Hodgkin lymphoma in children and adolescents, results of P9426: a report from the Children’s Oncology Group. Pediatr. Blood Cancer. 2012;59(7):1259-1265.
23. Кулева С.А., Анишкин М.Ю., Колыгин Б.А. Лимфома Ходжкина у детей и подростков: эффективность риск-адаптированного протоко- ла СПбЛХ-05. Детская онкология. 2007;3-4:16. [Kuleva S.A., Anishkin M.Yu., Kolygin B.A. Hodgkin’s lymphoma in children and teenagers: effectiveness of the risk-adapted protocol SPbHL- 05. Detskaya onkologiya. 2007;3-4:16.] (In Russ.)
24. Mauz-Körholz C., Metzger M.L., Kelly K.M., Schwartz C.L., Castellanos M.E., Dieckmann K. et al. Pediatric Hodgkin Lymphoma. J. Clin. Oncol. 2015;33(27):2975-2985.
25. Mauz-Körholz C., Hasenclever D., Dörffel W., Ruschke K., Pelz T., Voigt A. et al. Procarbazinefree OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin’s lymphoma: the GPOH-HD-2002 study. J. Clin. Oncol. 2010;28(23):3680-3686.
26. Wyns C., Curaba M., Vanabelle B., Van Langendonckt A., Donnez J. Options for fertility preservation in prepubertal boys. Hum. Reprod. Update. 2010;16(3):312-328.
27. Lee S.H., Shin C.H. Reduced male fertility in childhood cancer survivors. Ann. Pediatr. Endocrinol. Metab. 2013;18(4):168-172. 28. Kaaij M.A., Echten-Arends J., Simons A.H., Kluin- Nelemans H.C. Fertility preservation after chemotherapy for Hodgkin lymphoma. Hematol. Oncol. 2010;28(4):168-179.
28. da Cunha M.F., Meistrich M.L., Fuller L.M., Cundiff J.H., Hagemeister F.B., Velasquez W.S. et al. Recovery of spermatogenesis after treatment for Hodgkin’s disease: limiting dose of MOPP chemotherapy. Clin. Oncol. 1984;2(6):571-577.
29. Jacob A., Barker H., Goodman A., Holmes J. Recovery of spermatogenesis following bone marrow transplantation. Bone Marrow Transplant, 1998;22(3):277-279.
30. Meistrich M.L. Effects of chemotherapy and radiotherapy on spermatogenesis in humans. Fertil. Steril. 2013;100(5):1180-1186.
31. Dohle G.R. Male infertility in cancer patients: Review of the literature. Int. J. Urol. 2010;17(4):327-331.
32. Tal R., Botchan A., Hauser R., Yogev L., Paz G., Yavetz H. Follow-up of sperm concentration and motility in patients with lymphoma. Hum. Reprod. 2000;15(9):1985-1988.
33. Kinsella T.J. Effects of radiation therapy and chemotherapy on testicular function. Prog. Clin. Biol. Res. 1989;302:157-171.
34. Shalet S.M., Tsatsoulis A., Whitehead E., Read G. Vulnerability of the human Leydig cell to radiation damage is dependent upon age. J. Endocrinol. 1989;120(1):161-165.
35. Apperley J.F., Reddy N. Mechanism and management of treatment-related gonadal failure in recipients of high dose chemoradiotherapy. Blood Rev. 1995;9(2):93-116.
36. Green D.M., Kawashima T., Stovall M. Fertility of male survivors of childhood cancer: a report from the childhood cancer survivor study. J. Clin. Oncol. 2010;28(2):332–339.
37. Howell S.J., Shalet S.M. Spermatogenesis after cancer treatment: damage and recovery. J. Natl. Cancer Inst. Monogr. 2005;34:12-17.
38. Белогурова М.Б., Диникина Ю.В., Лисянская А.С. Осложнения противоопухолевой терапии со стороны репродуктивной функции в результате лечения онкологических заболеваний у мальчиков. Онкопедиатрия. 2014;4:40-48. [Belogurova M.B., Dinikina Yu.V., Lisyanskaya A.S. Complications of antitumor therapy from the side of reproductive function as a result of treatment of oncological diseases in boys. Onkopediatriya. 2014;4:40-48.] (In Russ.)
39. Oberfield S.E., Soranno D., Nirenberg A., Heller G., Allen J.C., David R. et al. Age at onset of puberty following high-dose central nervous system radiation therapy. Arch. Pediatr. Adolesc. Med. 1996;150(6):589-592.
40. Eichenauer D.A., Engert A. The evolving role of targeted drugs in the treatment of Hodgkin lymphoma. Expert Rev. Hematol. 2017;10(9):775-782.
41. Johannsdottir I.M., Karlstad O., Loge J.H., Fosså S.D., Kiserud C., Skurtveit S. Prescriptions of Antidepressants to Survivors of Cancer in Childhood, Adolescence, and Young Adulthood: A Population-Based Study. J. Adolesc. Young Adult Oncol. 2017;6(1):120-126.
42. Rach A.M., Crabtree V.M., Brinkman T.M., Zeltzer L., Marchak J.G., Srivastava D. et al. Predictors of fatigue and poor sleep in adult survivors of childhood Hodgkin’s lymphoma: a report from the Childhood Cancer Survivor Study. J. Cancer Surviv. 2017;11(2):256-263.
43. Hallak J., Mahran A.M., Agarwal A. Characteristics of cryopreserved semen from men with lymphoma. J. Assist. Reprod. Genet. 2000;17(10):591-594.
44. Marmor D., Elefant E., Dauchez C., Roux C. Semen analysis in Hodgkin’s disease before the onset of treatment. Cancer. 1986;57(10):1986-1987.
45. Padron O.F., Sharma R.K., Thomas A.J., Agarwal A. Effects of cancer on spermatozoa quality after cryopreservation: a 12-year experience. Fertil. Steril. 1997;67(2):326-331.
46. Paoli D., Gallo M., Rizzo F., Spanò M., Leter G., Lombardo F. et al. Testicular cancer and sperm DNA damage: short- and long-term effects of antineoplastic treatment. Andrology. 2015;3(1):122-128.
47. Marmor D., Elefant E., Dauchez C., Roux C. Semen analysis in Hodgkin’s disease before the onset of treatment. Cancer. 1986;57(10):1986-1987.
48. Schmidt K.T., Andersen C.Y. ISFP Practice Committee. Recommendations for fertility preservation in patients with lymphomas. Assist. Reprod. Genet. 2012;29(6):473-477.
49. Anderson R.A., Weddell A., Spoudeas H.A., Douglas C., Shalet S.M., Levitt G. et al. Do doctors discuss fertility issues before they treat young patients with cancer? Hum. Reprod. 2008;23(10):2246-2251.
50. Bahadur G. Cryobiology ethics of human reproduction. Semin. Reprod. Med. 2002;20(1):75-83.
51. Hovav Y., Dan-Goor M., Yaffe H., Almagor M. Electroejaculation before chemotherapy in adolescents and young men with cancer. Fertil. Steril. 2001;75(4):811-813.
52. Lee S.J., Schover L.R., Partridge A.H., Patrizio P., Wallace W.H., Hagerty K. et al. American Society of Clinical Oncology. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J. Clin. Oncol. 2006;24(18):2917-2931.
53. Frederickx V., Michiels A., Goossens E., De Block G., Van Steirteghem A.C., Tournaye H. Recovery, survival and functional evaluation by transplantation of frozen-thawed mouse germ cells. Hum. Reprod. 2004;19(4):948-953.
54. Nieschlag E. Clinical trials in male hormonal contraception. Contraception. 2010;82(5):457-470.
55. Винокуров А.А., Варфоломеева С.Р., Тарусин Д.И., Абдуллаев Р.Т., Гретцов Е.М., Луценко И.Н. и др. Фертильность подростков и молодых мужчин, излеченных от лимфомы Ходжкина. Злокачественные опухоли. 2012;1:18-27. [Vinokurov A.A., Varfolomeeva S.R., Tarusin D.I., Abdullaev R.T., Grettsov E.M., Lutsenko I.N. et al. Fertility of teenagers and young men cured from Hodgkin’s lymphoma. Zlokachestvennye opuholi. 2012;1:18-27.] (In Russ.)
56. Krawczuk-Rybak M., Solarz E., Wysocka J., Matysiak M., Gadomski A., Kazanowska B. et al. Testicular function after treatment for acute lymphoblastic leukemia (all) in prepubertal and pubertal boys. Pediatr. Hematol. Oncol. 2009;26(7):504-514.
Review
For citations:
Kuleva SA, Kurochkina DN, Zvyagintseva DA, Ivanova SV, Tsyrlina YV. Oncofertility in men cured of Hodgkin’s lymphoma as a child. Meditsinskiy sovet = Medical Council. 2019;(10):164-171. (In Russ.) https://doi.org/10.21518/2079-701X-2019-10-164-171