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Treatment of advanced Hodgkin lymphomas in adolescents and young adults: efficacy and toxicity issues

https://doi.org/10.17650/1818-8346-2014-9-1-11-18

Abstract

Hodgkin’s lymphoma (HL) is highly sensitive to chemo- and radiotherapy. Long-term tumor-free survival in patients with early stages is close to 95–98 %. Therapy results in patients with advanced stages is worse that requires an intensification of treatment and creates the issues
of late toxicity prevention. These problems are especially relevant in young adults with a life expectancy of 40 years or more. Escalated BEACOPP protocol developed by the German study group allows to achieve cure the majority of patients with advanced-stage Hodgkin’s lymphoma, but this regime has significant toxicity. It causes infertility in almost all patients. BEACOPP-14 with comparable activity contains less cumulative doses of potentially gonadotoxic alkylating agents. Efficacy and toxicity of this regime has been analyzed in 29 patients with prognostically unfavorable stages of HL (m – 13, f – 16) received 8 courses BEACOPP-14 without a dose reduction of cytostatics. The median age of patients was 24 (20–35) years. With a median follow-up of 32.8 (4–66) months, event-free survival was 92.8 %, disease-free – 96.2 %, and overall survival – 95.2 %. Of the 16 women included in the study, the menstrual cycle was restored in 14 patients during 3–6 months. 2 patients were not evaluated because of switch to more intensive chemotherapy in the early stages of treatment. Of the remaining 14 patients pregnancy occurred in 3 (18.7 %), delivery – in 2, abortion – in 1. Delivery was term, children born healthy. Most of the patients according to the doctors’ recommendations protects and continues to avoid pregnancy for 2 years after treatment. The data indicate a potentially less reproductive damaging of BEACOPP-14 in females retaining high anti-tumor efficacy.

About the Authors

Yu. V. Larina
Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Ministry of Health of Russia
Russian Federation


S. V. Minenko
Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Ministry of Health of Russia
Russian Federation


E. R. Biyachuev
Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Ministry of Health of Russia
Russian Federation


A. V. Pshonkin
Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Ministry of Health of Russia
Russian Federation


N. K. Khuazheva
S. P. Botkin City Clinical Hospital, Moscow Healthcare Department
Russian Federation


V. V. Ptushkin
Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Ministry of Health of Russia N. I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Russian Federation


References

1. Ries L.A.G., Harkins D., Krapcho M. et al. SEER Cancer Statistics Review, 1975–2003. Bethesda, Md: National Cancer Institute, 2006.

2. Macfarlane G.J., Evstifeeva T., Boyle P. et al. International patterns in the occurrence of Hodgkin's disease in children and young adult males. Int J Cancer 1995;61(2):165–9.

3. Ries L.A., Kosary C.L., Hankey B.F. et al., eds. SEER Cancer Statistics Review 1973– 1995. Bethesda, Md: National Cancer Institute, 1998.

4. Percy C.L., Smith M.A., Linet M. et al. Lymphomas and reticuloendothelial neoplasms. In: Ries L.A., Smith M.A., Gurney J.G. et al., eds. Cancer incidence and survival among children and adolescents: United States SEER Program 1975–1995. Bethesda, Md: National Cancer Institute, SEER Program, 1999. NIH Pub.No. 99-4649. Pp. 35–50.

5. European age-standardised rates calculated by the Statistical Information Team at Cancer Research UK, 2011 using data from GLOBOCAN, IARC, version 1.2.

6. Diehl V., Franklin J., Pfreundschuh M. et al. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin’s disease. N Engl J Med 2003;348(24):2386–95.

7. Canellos G.P., Anderson J.R., Propert K.J. et al. Chemotherapy of advanced Hodgkin’s disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med 1992;327(21):1478–84.

8. Gobbi P.G., Levis A., Chisesi T. et al. ABVD versus modified Stanford V versus MOPPEBVCAD with optional and limited radiotherapy in intermediate- and advancedstage Hodgkin’s lymphoma: final results of a multicenter randomized trial by the Intergruppo Italiano Linfomi. J Clin Oncol 2005;23:9198–9207.

9. Johnson P.W., Radford J.A., Cullen M.H. et al. Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin’s lymphoma: results of the United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519). J Clin Oncol 2005;23:9208–18.

10. Federico M., Luminari S., Iannitto E. et al. ABVD compared with BEACOPP compared with CEC for the initial treatment of patients with advanced Hodgkin’s lymphoma: results From the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. J Clin Oncol 2009;27:805–11.

11. Jenkin D., Chan H., Freedman M. et al. Hodgkin's disease in children: treatment results with MOPP and low-dose, extended-field irradiation. Cancer Treat Rep 1982;66(4):949–59.

12. Bhatia S., Robison L.L., Oberlin O. et al. Breast cancer and other second neoplasms after childhood Hodgkin's disease. N Engl J Med 1996;334(12):745–51.

13. Boice J.D. Jr. Radiation and breast carcinogenesis. Med Pediatr Oncol 2001;36:508–13.

14. van Leeuwen F.E., Klokman W.J., van’t Veer M.B. et al. Long-term risk of second malignancy in survivors of Hodgkin’s disease treated during adolescence or young adulthood. J Clin Oncol 2000;18:487–97.

15. Hodgson D.C. Late effects in the era of modern therapy for Hodgkin lymphoma. Hematology 2011;2011:323–9.

16. Donaldson S.S., Link M.P. Combined modality treatment with low-dose radiation and MOPP chemotherapy for children with Hodgkin's disease. J Clin Oncol 1987;5(5):742–9.

17. Schellong G., Pötter R., Brämswig J. et al. High cure rates and reduced long-term toxicity in pediatric Hodgkin's disease: the German-Austrian multicenter trial DAL-HD-90. The German- Austrian Pediatric Hodgkin's Disease Study Group. J Clin Oncol 1999;17(12):3736–44.

18. Dörffel W., Lüders H., Rühl U. et al. Preliminary results of the multicenter trial GPOH-HD 95 for the treatment of Hodgkin's disease in children and adolescents: analysis and outlook. Klin Padiatr 2003;215(3):139–45.

19. Bonadonna G., Santoro A. ABVD chemotherapy in the treatment of Hodgkin's disease. Cancer Treat Rev 1982;9(1):21–35.

20. Kelly K.M., Sposto R., Hutchinson R. 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):2596–603.

21. Gospodarowicz M.K., Meyer R.M. The management of patients with limited-stage classical Hodgkin lymphoma. Hematology Am Soc Hematol Educ Program 2006;2006:253–8.

22. Loeffler M., Brosteanu O., Hasenclever D. et al. Meta-analysis of chemotherapy versus combined modality treatment trials in Hodgkin’s disease. International Database on Hodgkin’s Disease Overview Study Group. J Clin Oncol 1998;16:818–29.

23. Borchmann P., Rancea M., Skoetz N. First-line treatment of advanced stage Hodgkin lymphoma. Final results of a systematic review and network meta-analysis. Hematologica 2013;98(Suppl 2):abstr. 004.

24. Engert A., Haverkamp H., Kobe C. Reduced-intensity chemotherapy and PETguided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 noninferiority trial. Lancet 2012;379(9828):1791–9.

25. Engert A., Diehl V., Franklin J. et al. Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin's lymphoma: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol 2009;27(27):4548–54.

26. Hudson M.M., Krasin M., Link M.P. et al. Risk-adapted, combined-modality therapy with VAMP/COP and response-based, involved-field radiation for unfavorable pediatric Hodgkin's disease. J Clin Oncol 2004;22(22):4541–50.

27. Mauz-Körholz C., Hasenclever D., Dörffel W. et al. Procarbazine-free 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):3680–6.

28. Семочкин С.В., Лория С.С., Румянцев А.Г., Сотников В.М. Лечение лимфомы Ходжкина у подростков и молодых взрослых. Онкогематология 2008;(1):18–26.

29. Kelly K.M., Sposto R., Hutchinson R. 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):2596–603.

30. Behringer K., Wildt L., Mueller H., Mattle V. No protection of the ovarian follicle pool with the use of GnRH-analogues or oral contraceptives in young women treated with escalated BEACOPP for advanced-stage Hodgkin lymphoma. Final results of a phase II trial from the German Hodgkin Study Group. Ann Oncol 2010;21(10):2052–60.

31. Adams M.J., Lipshultz S.E., Schwartz C. et al. Radiation-associated cardiovascular disease: manifestations and management. Semin Radiat Oncol 2003;13(3):346–56.

32. Friedman D.L., Constine L.S. Late effects of treatment for Hodgkin lymphoma. J Natl Compr Canc Netw 2006;4(3):249–57.

33. Maraldo M.V., Brodin N.P., Aznar M.C. et al. Estimated risk of cardiovascular disease and secondary cancers with modern highly conformal radiotherapy for early-stage mediastinal Hodgkin lymphoma. Ann Oncol 2013;(24):2113–8.

34. Engert A. Who should receive first-line BEACOPP therapy for Hodgkin lymphoma? Asco Post 2012;3(17).

35. Nachman J.B., Sposto R., Herzog P. et al. Randomized comparison of low-dose involvedfield radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. J Clin Oncol 2002;20(18):3765–71.


Review

For citations:


Larina Yu.V., Minenko S.V., Biyachuev E.R., Pshonkin A.V., Khuazheva N.K., Ptushkin V.V. Treatment of advanced Hodgkin lymphomas in adolescents and young adults: efficacy and toxicity issues. Oncohematology. 2014;9(1):11-18. (In Russ.) https://doi.org/10.17650/1818-8346-2014-9-1-11-18

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