Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2019; 18: 49-54
Эффективность и токсичность терапии детей и подростков с лимфомой Ходжкина по протоколу GPOH-HD-2002
https://doi.org/10.24287/1726-1708-2019-18-1-49-54Аннотация
Снижение долгосрочной выживаемости и фертильности - актуальные проблемы в лечении лимфомы Ходжкина (ЛХ) у детей и подростков. Частично эти проблемы можно решить редукцией лучевой терапии в группе пациентов с благоприятным прогнозом и заменой прокарбазина на этопозид и дакарбазин. В анализ были включены первичные пациенты в возрасте до 18 лет с впервые установленной классической ЛХ, получающие терапию в НМИЦ детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева Минздрава России. Данное исследование поддержано Независимым этическим комитетом и утверждено решением Ученого совета НМИЦ ДГОИ. Все пациенты получали терапию в период с 01.01.2012 по 01.12.2017 по модифицированному протоколу GPOH-HD-2002. В отличие от оригинального исследования, где девочки получали консолидацию блоками COPP, в нашем исследовании все пациенты вне зависимости от пола получали консолидацию блоками COPDAC. Анализировали результаты лечения 77 пациентов. Бессобытийная выживаемость (БСВ) составила 88% (95% ДИ - 76,2-93,9%). У мальчиков и девочек БСВ статистически не различалась - 86,9% (95% ДИ - 67,8-94,7%) и 88,7% (95% ДИ - 67,3-96,1%) соответственно (р = 0,9), но имела достоверные различия у пациентов с Е-поражением: у Е+ пациентов - 72,7% (95% ДИ - 28,4-89,6), а у Е-пациентов - 90,8% (95% ДИ - 77,8-96,2) (р = 0,04). Для оценки токсичности проанализированы 40 блоков ОЕРА и 44 блока COPDAC. Различий по показателю выживаемости мальчиков и девочек в нашем исследовании не выявлено. В индукционных блоках прокар-базин может быть полностью заменен на этопозид, а в консолидирующих блоках - на дакарбазин без выраженной токсичности. Вовлечение экстранодального участка, прилежащего или связанного с пораженным лимфатическим регионом, - прогностически неблагоприятный фактор, влияющий на снижение БСВ.
Список литературы
1. Swerdlow S., Campo E., Lee Harris N., Jaffe S.E., Pileri A.S., Stein H., et al. WHO Classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC, 2008.
2. Howlader N., Noone A.M., Krapcho M., Miller D., Bishop K., Altekruse S.F., et al. SEER Cancer Statistics Review, 1975- 2013, National Cancer Institute. Bethesda, MD. http://seer.cancer.gov/csr/1975_2013/, based on November 2015 SEER data submission, posted to the SEER web site, April 2016.
3. Smith M.A., Altekruse S.F., Adamson P.C., Reaman G.H., Seibel N.L. Declining childhood and adolescent cancer mortality. Cancer 2014; 120 (16): 2497-506.
4. Clavel J., Steliarova-Foucher E., Berger C., Danon S., Valerianova Z. Hodgkin's disease incidence and survival in European children and adolescents (1978-1997): report from the Automated Cancer Information System project. Eur J Cancer 2006; 42 (13): 2037-49.
5. Schellong G., Riepenhausen M., Ehlert K., Bramswig J., Dorffel W., Schmutzler R.K., et al. German Consortium for Hereditary Breast and Ovarian Cancer. Breast cancer in young women after treatment for Hodgkin's disease during childhood or adolescence - an observational study with up to 33-year follow-up. Dtsch Arztebl Int 2014; 111 (1-2): 3-9.
6. Castellino S.M., Geiger A.M., Mertens A.C., Leisenring W.M., Tooze J.A., Goodman P., et al. Morbidity and mortality in longterm survivors of Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study. Blood 2011; 117 (6): 1806-16.
7. Kreuser E.D., Xiros N., Hetzel W.D., Heimpel H. Reproductive and endocrine gonadal capacity in patients treated with COPP chemotherapy for Hodgkin's disease. J Cancer Res Clin Oncol 1987; 113 (3): 260-6.
8. Bramswig J.H., Heimes U., Heier-mann E., Schlegel W., Nieschlag E., Schellong G. The effects of different cumulative doses of chemotherapy on testicular function: Results in 75 patients treated for Hodgkin's disease during childhood or adolescence. Cancer 1990; 65 (6): 1298-302.
9. Gerres L., Bramswig J.H., Schlegel W., Jurgens H., Schellong G. The effects of etoposide on testicular function in boys treated for Hodgkin's disease. Cancer 1998; 83 (10): 2217-22.
10. Biasoli I., Falorio S., Luminari S., Spec-tor N., Federico M. Fertility in female survivors of Hodgkin's Lymphoma. Rev Bras Hematol Hemoter 2012; 34 (1): 48-53.
11. Mauz-Korholz C., Hasenclever D., Dorf-fel W., Ruschke K., Pelz T., Voigt A., et al. Procarbazine-free OEPACOPDAC 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.
12. Trotti A., Byhardt R., Stetz J., Gwede C., Corn B., Fu K., et al. Common toxicity criteria: version 2.0. an improved reference for grading the acute effects of cancer treatment: impact on radiotherapy. Int J Radiat Oncol Biol Phys 2000 Apr 1; 47 (1): 13-47.
13. Gray R.J. A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1988; 16: 1141-54.
14. Евстратов Д.А., Жарков П.А., Пшонкин А.В., Абугова Ю.Г., Дьяконова Ю.Ю., Ершов Н.М. и др. Венозные тромбозы у детей и подростков с лимфомой Ходжкина. Педиатрия 2018; 97 (4): 30-6.
Pediatric Hematology/Oncology and Immunopathology. 2019; 18: 49-54
Efficacy and toxicity of the treatment of children and adolescents with Hodgkin Lymphoma by GPOH-HD-2002 protocol
https://doi.org/10.24287/1726-1708-2019-18-1-49-54Abstract
The reduction of long-term survival and fertility is still a problem in management of Hodgkin lymphoma in children and adolescents. These problems are partly solved by reduction of radiotherapy and changing procarbazine on etoposide and dacarbazine. We analyzed medical data of patients with HL < 18 years that were treated by modified OEPA-COPDAC protocol since 1.01.2012 to 01.12.2017. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. All patients despite gender didn't receive procarbazine. We analyzed data of 77 patients. Event-free survival (EFS) was 88% (95% CI 76.2-93.9%). EFS didn't differ between boys and girls 86.9% (95% CI 67.8-94.7%) and 88.7% (95% CI 67.3-96.1%) respectively (р = 0,9). EFS was significantly higher in patients without E-lesions compared with patients with E-lesions 90.8% (95% CI 77.8-96.2) and 72.7% (95% CI 28.4-89.6) respectively (p = 0.04). We analyzed toxicity of 40 cycles OEPA and 44 cycles COPDAC. Toxicity was acceptable. In our study we didn't detect significant difference in EFS in boys and girls. Procarbazine can be safely changed on etoposide in OPPA and dacarbazine in COPP in boys and girls with HL. E-lesions is a risk factor of inferior EFS.
References
1. Swerdlow S., Campo E., Lee Harris N., Jaffe S.E., Pileri A.S., Stein H., et al. WHO Classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC, 2008.
2. Howlader N., Noone A.M., Krapcho M., Miller D., Bishop K., Altekruse S.F., et al. SEER Cancer Statistics Review, 1975- 2013, National Cancer Institute. Bethesda, MD. http://seer.cancer.gov/csr/1975_2013/, based on November 2015 SEER data submission, posted to the SEER web site, April 2016.
3. Smith M.A., Altekruse S.F., Adamson P.C., Reaman G.H., Seibel N.L. Declining childhood and adolescent cancer mortality. Cancer 2014; 120 (16): 2497-506.
4. Clavel J., Steliarova-Foucher E., Berger C., Danon S., Valerianova Z. Hodgkin's disease incidence and survival in European children and adolescents (1978-1997): report from the Automated Cancer Information System project. Eur J Cancer 2006; 42 (13): 2037-49.
5. Schellong G., Riepenhausen M., Ehlert K., Bramswig J., Dorffel W., Schmutzler R.K., et al. German Consortium for Hereditary Breast and Ovarian Cancer. Breast cancer in young women after treatment for Hodgkin's disease during childhood or adolescence - an observational study with up to 33-year follow-up. Dtsch Arztebl Int 2014; 111 (1-2): 3-9.
6. Castellino S.M., Geiger A.M., Mertens A.C., Leisenring W.M., Tooze J.A., Goodman P., et al. Morbidity and mortality in longterm survivors of Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study. Blood 2011; 117 (6): 1806-16.
7. Kreuser E.D., Xiros N., Hetzel W.D., Heimpel H. Reproductive and endocrine gonadal capacity in patients treated with COPP chemotherapy for Hodgkin's disease. J Cancer Res Clin Oncol 1987; 113 (3): 260-6.
8. Bramswig J.H., Heimes U., Heier-mann E., Schlegel W., Nieschlag E., Schellong G. The effects of different cumulative doses of chemotherapy on testicular function: Results in 75 patients treated for Hodgkin's disease during childhood or adolescence. Cancer 1990; 65 (6): 1298-302.
9. Gerres L., Bramswig J.H., Schlegel W., Jurgens H., Schellong G. The effects of etoposide on testicular function in boys treated for Hodgkin's disease. Cancer 1998; 83 (10): 2217-22.
10. Biasoli I., Falorio S., Luminari S., Spec-tor N., Federico M. Fertility in female survivors of Hodgkin's Lymphoma. Rev Bras Hematol Hemoter 2012; 34 (1): 48-53.
11. Mauz-Korholz C., Hasenclever D., Dorf-fel W., Ruschke K., Pelz T., Voigt A., et al. Procarbazine-free OEPACOPDAC 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.
12. Trotti A., Byhardt R., Stetz J., Gwede C., Corn B., Fu K., et al. Common toxicity criteria: version 2.0. an improved reference for grading the acute effects of cancer treatment: impact on radiotherapy. Int J Radiat Oncol Biol Phys 2000 Apr 1; 47 (1): 13-47.
13. Gray R.J. A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1988; 16: 1141-54.
14. Evstratov D.A., Zharkov P.A., Pshonkin A.V., Abugova Yu.G., D'yakonova Yu.Yu., Ershov N.M. i dr. Venoznye trombozy u detei i podrostkov s limfomoi Khodzhkina. Pediatriya 2018; 97 (4): 30-6.
