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Современные возможности диагностики и лечения диффузной В-крупноклеточной лимфомы у детей и подростков: результаты НИИ детской онкологии и гематологии, международный опыт
Современные возможности диагностики и лечения диффузной В-крупноклеточной лимфомы у детей и подростков: результаты НИИ детской онкологии и гематологии, международный опыт
Левашов А.С., Ковригина А.М., Валиев Т.Т. и др. Современные возможности диагностики и лечения диффузной В-крупноклеточной лимфомы у детей и подростков: результаты НИИ детской онкологии и гематологии, международный опыт. Современная Онкология. 2015; 17 (4): 34–44.
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Аннотация
В настоящее время опубликованы результаты лечения детей с диффузной В-крупноклеточной лимфомой (ДВККЛ) по различным программам терапии (FAB/LMB96 ± ритуксимаб, B-NHL-BFM90/95, B-NHL-2004m). Но прогностическая значимость маркеров, таких как non-GCB субтип ДВККЛ, экспрессия C-MYC, BCL2, pSTAT3, коэкспрессия BCL2/C-MYC, наличие реаранжировки генов C-MYC, BCL-2, BCL-6, кореаранжировки генов C-MYC/BCL-2, у детей и подростков остается неизвестной.
В данной статье представлены результаты лечения детей с ДВККЛ по протоколам IDM-NHL-BFM90, B-NHL-BFM95 ± ритуксимаб c учетом морфоиммунологических особенностей опухоли.
Материалы и методы. С 1994 по 2015 г. 51 пациент (дети и подростки) с ДВККЛ был включен в исследования IDM-NHL-BFM90, B-NHL-BFM95 ± ритуксимаб. Соотношение мальчиков и девочек составило 2/1. Средний возраст 9,9±0,5 года (от 2 до 16 лет). Медиана возраста 10 лет. Стадии заболевания III и IV выявлены у 29 (56,9%) детей, R3–R4 группы риска – у 26 (50,9%). GCB/non-GCB субтипы ДВККЛ оценивались с помощью иммуногистохимических алгоритмов Hans, Tally и Visco-Young. C-MYC-позитивный вариант ДВККЛ определялся при уровне экспрессии более 40%, BCL-2-позитивный вариант ДВККЛ – при уровне экспрессии более 70%, pSTAT3-позитивный вариант – при уровне экспрессии более 50%. Реаранжировки генов C-MYC, BCL-2, BCL-6 определялись методом FISH с использованием локус-специфических проб.
Результаты. GCB и non-GCB субтипы ДВККЛ были выявлены соответственно в 13 (54,2%) и 11 (45,8%) из 24 случаев; в 10 (41,7%) и 14 (58,3%) из 24 случаев – в соответствии с диагностическим алгоритмом Hans; 10 (43,5%) и 13 (56,5%) из 23 – в соответствии с алгоритмом Visco-Young; в 7 (63,6%) и 4 (36,4%) из 11 случаев – в соответствии с алгоритмом Tally. Был отмечен тренд к выявлению различий в определении GCB/non-GCB вариантов ДВККЛ (р=0,058) при использовании диагностических алгоритмов Hans, Tally, Visco-Young (у 3 пациентов выявлен GCB вариант ДВККЛ в соответствии с алгоритмом Tally, non-GCB – в соответствии с алгоритмами Hans, Visco-Young). Десять (62,5%) из 16 образцов ДВККЛ были позитивны для С-MYC, 9 (40,9%) из 22 – для BCL2, 2 (18,2%) из 11 – с коэкспрессией BCL2/C-MYC, 1 (9,1%) из 11 – для pSTAT3. Реаранжировка гена С-MYC выявлена у 3 (20%) из 15 пациентов. Отмечена статистически достоверная взаимосвязь между уровнем экспрессии C-MYC выше 70% и наличием реаранжировки гена С-MYC в опухоли у детей с III–IV стадиями заболевания, R3–R4 группами риска (p<0,05). Реаранжировки генов BCL2 и BCL6 не выявлены. В группе пациентов, получивших лечение по программе B-NHL-BFM95 ± ритуксимаб, 5-летняя общая выживаемость, бессобытийная выживаемость составили 90,3±5,3% при средней продолжительности наблюдения в 63,3±7,9 мес, безрецидивная – 100% при средней продолжительности наблюдения 69,5±7,9 мес. Не было отмечено какого-либо достоверного влияния исследуемых маркеров на показатели общей, бессобытийной, безрецидивной выживаемости.
Заключение. Число пациентов в данном исследовании недостаточно, чтобы оценить достоверную прогностическую значимость данных маркеров, но высокоинтенсивная программа терапии B-NHL-BFM95 ± ритуксимаб показала хороший терапевтический эффект у наших пациентов. Исследование будет продолжено.
Ключевые слова: диффузная В-крупноклеточная лимфома, диагностика, лечение, дети, подростки.
Design/Methods. From 1994 to 2015 fifty one pediatric patients with DLBCL were included in trials IDM-NHL-BFM90, B-NHL-BFM95 ± rituximab. Male/female ratio was 2/1. Median age – 9.9±0.5 years (range from 2 till 16). Stage III-IV were revealed in 29 patients (56.9%), R3-R4-risk group – in 26 (50.9%). GCB/non-GCB DLBCL subtypes were assessed by Hans, Tally and Visco-Young immunohistochemical algorithms. Cutoff values of 40% for MYC, 70% for BCL2, 50% for pSTAT3 were established. MYC gene rearrangement was assessed by FISH using locus-specific MYC (8q24) tricolor breakapart probe, MYC (8q24) SE8 control probe and locus-specific MYC, BCL2, BCL6 dual-color breakapart probes.
Results. GCB/non-GCB DLBCL subtypes were revealed in 13 (54.2%) and 11 (45.8%) out of 24 cases; in 10 (41.7%) and 14 (58.3%) out of 24 cases according to Hans algorithm, 10 (43.5%) and 13 (56.5%) out of 23 cases according to Visco-Young algorithm; in 7 (63.6%) and 4 (36.4%) out of 11 cases according to Tally algorithm. There was a trend to determine the difference between GCB/non-GCB subgroups of DLBCL according immunohistochemical algorithms (p=0.058). Ten (62.5%) out of 16 DLBCL samples were positive for MYC, 9 (40.9%) out of 22 – for BCL2, 2 (18.2%) out of 11 – for BCL2/C-MYC coexpression, 1 (9.1%) out of 11 – for pSTAT3. MYC gene rearrangement was revealed in 3 (20%) out of 15 patients. There was determined a statistically significant relationship between MYC expression >70% and MYC gene rearrangement in patients with III – IV stages of disease and R3 – R4 risk group. BCL2 and BCL-6 gene rearrangements were not revealed. Five-year overall survival (OS), event-free survival (EFS) were 90.3±5.3%, a median follow-up was 63.3±7.9 months, relapse-free (RFS) was 100%, a median follow-up was 69.5±7.9 months. There is not revealed any influence of investigated markers on OS, EFS and RFS.
Conclusion. Number of patients in this study is not enough to estimate authentic prognostic significance of these markers but high-intensive B-NHL-BFM95 ± rituximab chemotherapy showed good therapeutic effect in our patients. This study will be continued.
Key words: diffuse large B-cell lymphoma, diagnosis, treatment, children, adolescents.
В данной статье представлены результаты лечения детей с ДВККЛ по протоколам IDM-NHL-BFM90, B-NHL-BFM95 ± ритуксимаб c учетом морфоиммунологических особенностей опухоли.
Материалы и методы. С 1994 по 2015 г. 51 пациент (дети и подростки) с ДВККЛ был включен в исследования IDM-NHL-BFM90, B-NHL-BFM95 ± ритуксимаб. Соотношение мальчиков и девочек составило 2/1. Средний возраст 9,9±0,5 года (от 2 до 16 лет). Медиана возраста 10 лет. Стадии заболевания III и IV выявлены у 29 (56,9%) детей, R3–R4 группы риска – у 26 (50,9%). GCB/non-GCB субтипы ДВККЛ оценивались с помощью иммуногистохимических алгоритмов Hans, Tally и Visco-Young. C-MYC-позитивный вариант ДВККЛ определялся при уровне экспрессии более 40%, BCL-2-позитивный вариант ДВККЛ – при уровне экспрессии более 70%, pSTAT3-позитивный вариант – при уровне экспрессии более 50%. Реаранжировки генов C-MYC, BCL-2, BCL-6 определялись методом FISH с использованием локус-специфических проб.
Результаты. GCB и non-GCB субтипы ДВККЛ были выявлены соответственно в 13 (54,2%) и 11 (45,8%) из 24 случаев; в 10 (41,7%) и 14 (58,3%) из 24 случаев – в соответствии с диагностическим алгоритмом Hans; 10 (43,5%) и 13 (56,5%) из 23 – в соответствии с алгоритмом Visco-Young; в 7 (63,6%) и 4 (36,4%) из 11 случаев – в соответствии с алгоритмом Tally. Был отмечен тренд к выявлению различий в определении GCB/non-GCB вариантов ДВККЛ (р=0,058) при использовании диагностических алгоритмов Hans, Tally, Visco-Young (у 3 пациентов выявлен GCB вариант ДВККЛ в соответствии с алгоритмом Tally, non-GCB – в соответствии с алгоритмами Hans, Visco-Young). Десять (62,5%) из 16 образцов ДВККЛ были позитивны для С-MYC, 9 (40,9%) из 22 – для BCL2, 2 (18,2%) из 11 – с коэкспрессией BCL2/C-MYC, 1 (9,1%) из 11 – для pSTAT3. Реаранжировка гена С-MYC выявлена у 3 (20%) из 15 пациентов. Отмечена статистически достоверная взаимосвязь между уровнем экспрессии C-MYC выше 70% и наличием реаранжировки гена С-MYC в опухоли у детей с III–IV стадиями заболевания, R3–R4 группами риска (p<0,05). Реаранжировки генов BCL2 и BCL6 не выявлены. В группе пациентов, получивших лечение по программе B-NHL-BFM95 ± ритуксимаб, 5-летняя общая выживаемость, бессобытийная выживаемость составили 90,3±5,3% при средней продолжительности наблюдения в 63,3±7,9 мес, безрецидивная – 100% при средней продолжительности наблюдения 69,5±7,9 мес. Не было отмечено какого-либо достоверного влияния исследуемых маркеров на показатели общей, бессобытийной, безрецидивной выживаемости.
Заключение. Число пациентов в данном исследовании недостаточно, чтобы оценить достоверную прогностическую значимость данных маркеров, но высокоинтенсивная программа терапии B-NHL-BFM95 ± ритуксимаб показала хороший терапевтический эффект у наших пациентов. Исследование будет продолжено.
Ключевые слова: диффузная В-крупноклеточная лимфома, диагностика, лечение, дети, подростки.
________________________________________________
Design/Methods. From 1994 to 2015 fifty one pediatric patients with DLBCL were included in trials IDM-NHL-BFM90, B-NHL-BFM95 ± rituximab. Male/female ratio was 2/1. Median age – 9.9±0.5 years (range from 2 till 16). Stage III-IV were revealed in 29 patients (56.9%), R3-R4-risk group – in 26 (50.9%). GCB/non-GCB DLBCL subtypes were assessed by Hans, Tally and Visco-Young immunohistochemical algorithms. Cutoff values of 40% for MYC, 70% for BCL2, 50% for pSTAT3 were established. MYC gene rearrangement was assessed by FISH using locus-specific MYC (8q24) tricolor breakapart probe, MYC (8q24) SE8 control probe and locus-specific MYC, BCL2, BCL6 dual-color breakapart probes.
Results. GCB/non-GCB DLBCL subtypes were revealed in 13 (54.2%) and 11 (45.8%) out of 24 cases; in 10 (41.7%) and 14 (58.3%) out of 24 cases according to Hans algorithm, 10 (43.5%) and 13 (56.5%) out of 23 cases according to Visco-Young algorithm; in 7 (63.6%) and 4 (36.4%) out of 11 cases according to Tally algorithm. There was a trend to determine the difference between GCB/non-GCB subgroups of DLBCL according immunohistochemical algorithms (p=0.058). Ten (62.5%) out of 16 DLBCL samples were positive for MYC, 9 (40.9%) out of 22 – for BCL2, 2 (18.2%) out of 11 – for BCL2/C-MYC coexpression, 1 (9.1%) out of 11 – for pSTAT3. MYC gene rearrangement was revealed in 3 (20%) out of 15 patients. There was determined a statistically significant relationship between MYC expression >70% and MYC gene rearrangement in patients with III – IV stages of disease and R3 – R4 risk group. BCL2 and BCL-6 gene rearrangements were not revealed. Five-year overall survival (OS), event-free survival (EFS) were 90.3±5.3%, a median follow-up was 63.3±7.9 months, relapse-free (RFS) was 100%, a median follow-up was 69.5±7.9 months. There is not revealed any influence of investigated markers on OS, EFS and RFS.
Conclusion. Number of patients in this study is not enough to estimate authentic prognostic significance of these markers but high-intensive B-NHL-BFM95 ± rituximab chemotherapy showed good therapeutic effect in our patients. This study will be continued.
Key words: diffuse large B-cell lymphoma, diagnosis, treatment, children, adolescents.
Полный текст
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39. Tzankov A, Xu-Monette Z, Gerhard M. Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP. Modern Pathol 2014; 27: 958–71.
40. Valera A, Colomo L, Martinez A. ALK-positive large B-cell lymphomas express a terminal B-cell differentiation program and activated STAT3 but lack MYC rearrangements. Modern Pathol 2013; 26: 1329–37.
41. Visco C, Tzankov A, Xu-Monette Z. Patients with diffuse large B-cell lymphoma of germinal center origin with BCL2 translocations have poor outcome, irrespective of MYC status: a report from an International DLBCL rituximab-CHOP consortium program study. Haematologica 2013; 98 (2): 255–63.
42. Wu ZL, Song YQ, Shi YF. High nuclear expression of STAT3 is associated with unfavorable prognosis in diffuse large B-cell lymphoma. J Hematol Oncol 2011; 4 (31). http://www.jhoonline.org/content/pdf/1756-8722-4-31.pdf
43. Xie M, Wei Y, Ley Y. The prognostic significance of tumor-associated macrophages and NK cells in patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood 2014; 124 (21). http://www.bloodjournal.org/content/124/21/5390.full.pdf
44. Yamamoto W, Nakamura N, Tomita N. Human leukocyte antigen – DR expression on flow cytometry and tumor associated macrophages in diffuse large B cell lymphoma treated by: rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone therapy: retrospective cogort study. Leukemia/Lymphoma 2014; 55 (12): 2721–7.
45. Imbach P, Kuhne Th, Arceci R. Pediatric Oncology. A comprehensive guide. 2006; p. 61–9.
46. Rosolen A, Perkins SL, Pinkerton CR. Revised International Pediatric Non-Hodgkin Lymphoma Staging System. J Clin Oncol 2015; 33 (18): 2106–11.
47. Apostolopoulos DJ, Papandrianos NI, Symeonidis A. Technetium-99m depreotide imaging by single photon emission tomography/low resolution computed tomography in malignant lymphomas: comparison with gallium-67 citrate. Ann Nuclear Med 2010; 24: 639–47.
48. Bardi E, Csoka M, Garai I. Value of FDG-PET/CT examinations in different cancers of children, focusing on lymphomas. Pathol Oncol Res 2014; 20: 139–43.
49. Dabaja B, Phan J, Mawlawi O. Clinical implications of PET-negative residual CT masses after chemotherapy for diffuse large B-cell lymphoma. Leukemia Lymphoma 2013; 54 (12): 2631–8.
50. Furth C, Steffen IG, Erdrich AS. Explorative analyses on the value of interim PET for prediction of response in pediatric and adolescent non-Hodgkin lymphoma patients. EJNMMI res 2013; 3 (71). http://www.ejnmmires.com /content/3/1/71
51. Lange J, Burghardt B. Treatment of adolescents with aggressive B-cell malignancies: the pediatric experience. Curr Hematol Malign Rep 2013; 8 (3): 226–35.
52. Scott R, Jo-Anne V, Aliakbar S. Characteristic expression patterns of TCL1, CD38, CD44 identify aggressive lymphomas harboring a MYC translocation. Am J Surg Pathol 2008; 32 (1): 113–22.
53. Green TM, Nielsen O, de Stricker K. High levels of nuclear MYC protein predict the presence of MYC rearrangement in diffuse large B-cell lymphoma. Am J Surg Pathol 2012; 36 (4): 612–9.
54. Kondratieva S, Duraisamy S, Unitt CL. Aberrant expression of the dendritic cell marker TNFAIP2 by the malignant cells of Hodgkin lymphoma and primary mediastinal large B-cell lymphoma distinguishes these tumor types from morphologically and phenotypically similar lymphomas. Am J Surg Pathol 2011; 35 (10): 1531–9.
55. Togunaga T, Tomita A, Sugimoto K. De novo diffuse large B-cell lymphoma with a CD20 immunohistochemistry-positive and flow cytometry-negative phenotype: molecular mechanisms and correlation with rituximab sensitivity. Cancer Sci 2014; 105 (1): 35–43.
56. Song G, Cho WC, Gu L. Increased CD59 protein expression is associated with the outcome of patients with diffuse large B-cell lymphoma treated with R-CHOP. Med Oncol 2014; 31 (56). http://link.springer.com.sci-hub.org/article/10.1007/s12032-014-0056-y
57. Fen Liu, Ding H, Jin X. FCGR3A 158 V/F polymorphism and response to frontline R-CHOP therapy in diffuse large B-cell lymphoma. DNA Cell Biol 2014; 33: 616–23.
58. Morschhauser FA, Cartron G, Thieblemont C. Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large B-cell lymphoma or mantle-cell lymphoma: results from the Phase II GAUGUIN study. J Clin Oncol 2013; 31: 2912–9.
59. Coiffier B, Radford J, Bosly A. A multicentre, phase II trial ofatumumab monotherapy in relapsed/progressive diffuse large B-cell lymphoma. Br J Hematol 2013; 163: 334–42.
60. Viardot A, Goebeler M, Hess G. Treatment of relapsed/refractory diffuse large B cell lymphoma with the bispecific T-cell engager (BiTE) antibody construct blinatumomab: primary analysis results from an open-label, phase II study. ASH annual meeting abstracts book. 2014; 4460. https://ash.confex.com/ ash/2014/webprogram/Paper 68589. html
61. Portell CA, Wenzell CM, Advani AS. Clinical and pharmacologic aspects of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia. Clin Pharmacol Adv Appl 2013; 5: 5–11.
62. Schlegel P, Lang P, Zugmaier G. Pediatric posttransplant relapsed/refractory B-precursor acute lymphoblastic leukemia shows durable remission by therapy with the T-cell engaging bispecific antibody blinatumomab. Haematologica 2014; 99 (7): 1212–8.
63. Stackelberg A, Locatelli F, Zugmaier G. Phase 1/2 study in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) receiving blinatumomab treatment. ASH annual meeting abstracts book. 2014; 2292. https://ash.confex. com/ash/ 2014/webprogram/Paper69576.html
64. Schuster FR, Stanglmaier M, Woessmann W. Immunotherapy with trifunctional anti-CD20 x anti-CD3 antibody FBTA05 (Lymphomun) in pediatric high-risk patients with recurrent CD20-positive B-cell malignancies. Br J Haematol 2015; 169 (1): 90–102.
65. Kochenderfer JN, Dudley ME, Kassim SH. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T-cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol 2014. http://jco.ascopubs.org/content/early/2014/08/25/JCO. 2014.56.2025. full.pdf
66. Wang Y, Zhang WY, Han QW. Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells. Clin Immunol 2014; 155: 160–75.
67. Maude SL, Teachey DT, Porter DA. Chimeric antigen receptor (CAR) modified N cells induce durable remissions in children with relapsed/refractory ALL. Blood 2015; 125 (26): 4017–23.
2. Burkhardt В, Oschlies I, Klapper W. Non-Hodgkin’s lymphoma in adolescents: experiences in 378 adolescent NHL patients treated according to pediatric NHL-BFM protocols. Leukemia. 2011; 25: 153–60.
3. Kovrigina A.M., Probatova N.A. Limfoma Khodzhkina i krupnokletochnye limfomy. M.: Meditsinskoe informatsionnoe agentstvo, 2007; s. 212. [in Russian]
4. Swerdlow SH, Campo E, Harris NL. WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues, Fourth edition. 2008.
5. Reiter A, Klapper W. Recent advances in the understanding and management of diffuse large B-cell lymphoma in children. Br J Hematol 2008; 142: 329–47.
6. Jaffe ES, Pittaluga S. Aggressive B-cell lymphomas: a review of new and old entities in the WHO classification. Hematology 2011; p. 506–14.
7. Heerema NA, Bernheim AB, Lim MS. Meeting report, State of the art and future needs in cytogenetic/molecular genetics/arrays in childhood lymphoma: summary report of workshop at the first international symposium on childhood and adolescent non-Hodgkin lymphoma. Ped Blood Cancer 2005; 45: 616–22.
8. Oschlies I, Klapper W, Zimmermann M. Diffuse large B-cell lymphoma in pediatric patients belongs predominantly to the germinal-center type B-cell lymphomas: a clinicopathologic analysis of cases included in the German BFM (Berlin-Francfurt-Munster) multicenter trial. Blood 2006; 107 (10): 4047–52.
9. Miles R, Raphael M, McCarthy K. Pediatric diffuse large B-cell lymphoma demonstrates a high proliferation index, frequent c-myc protein expression, and a high incidence of germinal center subtype: report of the French-American-British (FAB) International Study Group. Ped Blood Cancer 2008; 51 (3): 369–74.
10. Roschewski M, Staudt LM, Wilson WH. Diffuse large B-cell lymphoma – treatment approaches in the molecular era. Nat Rev Clin Oncol 2014; 11 (1): 12–23.
11. Schneider C, Pasqualucci L, Dalla-Favera R. Molecular pathogenesis of diffuse large B-cell lymphoma. Semin Diagn Pathol 2011; 28: 167–77.
12. Baryshnikov A.Iu., Valiev T.T., Gubin A.N. Limfomy u detei: prakticheskoe rukovodstvo. Pod red. G.L.Mentkevicha, S.A.Maiakovoi. M.: Prakticheskaia meditsina, 2014. [in Russian]
13. Mentkevich G.L., Maiakova S.A. Limfomy u detei. M.: Prakticheskaia meditsina, 2014. [in Russian]
14. Laver JH, Kraveka JM, Hutchison RE. Advanced-Stage Large-Cell Lymphoma in Children and Adolescents: Results of a Randomized Trial Incorporating intermediate-Dose Methotrexate and High-Dose Cytarabine in the Maintenance Phase of the APO Regimen: A Pediatric Oncology Group Phase III Trial. J Clin Oncol 2005; 23 (3): 541–7.
15. Tsurusawa M, Mori T, Kikuchi A. Improved treatment results of Children with B-cell non-Hodgkin lymphoma: a report from Japanese pediatric leukemia/lymphoma study group B-NHL03 study. Ped Blood Cancer 2014; 61: 1215–21.
16. Goldman S, Smith L, Anderson JR. Rituximab and FAB/LMB96 chemotherapy in children with stage III/IV B-cell non-Hodgkin lymphoma: a Children’s Oncology group report. Leukemia 2013; 27: 1174–7.
17. Barth MJ, Goldman S, Smith L. Rituximab pharmacokinetics in children and adolescents with de novo intermediate and advanced mature B-cell lymphoma/leukemia: a Children’s Oncology group report. Br J Haematol 2013; 162: 678–83.
18. Samochatova E.V., Shelikhova L.N., Miakova N.V. Vozmozhnosti i problemy sovremennoi terapii nekhodzhkinskikh limfom u detei i podrostkov. Pediatriia. 2011; 90 (4): 37–43. [in Russian]
19. Samochatova E.V., Shelikhova L.N., Belogurova M.B. Kombinirovannaia khimioimmunoterapiia bol'nykh nekhodzhkinskimi limfomami iz zrelykh V-kletok vozrastnoi gruppy do 18 let: rezul'taty mnogotsentrovogo issledovaniia NKhL2004m s primeneniem rituksimaba i modifitsirovannogo protokola B-NKhL BFM 90. Onkogematologiia. 2009; 3: 4–14. [in Russian]
20. Samochatova E.V., Shelikhova L.N., Miakova N.V. Lechenie diffuznoi B-krupnokletochnoi limfomy u detei s primeneniem intensivnoi khimioterapii s rituksimabom: predvaritel'nye rezul'taty. Detskaia onkologiia. 2007; 3–4: 51–6. [in Russian]
21. Klapper W, Kreuz M, Kohler CW. Patient age at diagnosis is associated with the molecular characteristics of diffuse large B-cell lymphoma. Blood 2012; 119 (8): 1882–7.
22. Chen Y, Sun XF, Cai RQ. Germinal-center type B-cell classification and clinical characteristics of Chinese pediatric diffuse large B-cell lymphoma: a report of 76 cases. Chin J Cancer 2013; 32 (10): 561–6.
23. Poirel HA, Cairo MS, Heerema NA. Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell non-Hodgkin’s lymphoma: results of the FAB/LMB 96 international study. Leukemia 2009; 23 (2): 323–31.
24. Reiter A, Schrappe M, Tieman M. Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy: a report of the Berlin-Frankfurt-Munster group Trial NHL-BFM90. Blood 1999; 94 (10): 3294–306.
25. Woessmann W, Seidemann K, Mann G, Zimmermann M. The impact of the methotrexate administration schedule and dose in the treatment of children and adolescents with B-cell neoplasms: a report of the BFM group study NHL-BFM95. Blood 2005; 105: 948–58.
26. Meyer PN, Fu K, Greiner TG. Immunohistochemical methods for predicting cell of origin and survival in patients with diffuse large B-cell lymphoma treated with rituximab. J Clin Oncol 2011; 29 (2): 200–7.
27. Perry AM, Zdravko M. Biological prognostic markers in diffuse large B-cell lymphoma. Cancer Control 2012; 19 (3): 214–26.
28. Culpin RE, Sieniawski M, Angus B. Prognostic significance of immunohistochemistry-based markers and algorithms in immunochemotherapy-treated diffuse large B cell lymphoma patients. Histopathology 2013; 63: 788–801.
29. Visco Y, Li Y, Xu-Monette ZY. Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma: a report from the International DLBCL Rituximab-CHOP Consortium Prorram Study. Leukemia 2012; 26 (9): 2103–13.
30. Cox CM, Di Napoli A, Scarpino S. Clinicopathologic characterization of diffuse large B cell lymphoma with an associated serum monoclonal IgM component. PLOS one 2014. http://www.plosone.org/article/fetchObject.action?uri=info:doi/ 10.1371/journal.pone.0093903&representation=PDF
31. Hu S, Xu-Monette ZY, Balasubramanyam A. CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature: a report from the International DLBCL Rituximab-CHOP Consortium Program Study. Blood 2013; 121: 2715–24.
32. Hu S, Xu-Monette ZY, Tzankov A. MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from the international DLBCL Rituximab-CHOP consortium program. Blood 2013; 121 (20): 4021–31.
33. Ichikava S, Fukuhara N, Katsushima H. Association between BACH2 expression and clinical prognosis in diffuse large B cell lymphoma. Cancer Sci 2014; 105 (4): 437–44.
34. Laurent C, Do C, Gascoyne RD. Anaplastic lymphoma kinase – positive diffuse large B-cell lymphoma: a rare clinicopathologic entity with poor prognosis. J Clin Oncol 2009; 27 (25): 4211–6.
35. Miyazaki K, Yamaguchi M, Suzuki R. CD5-positive diffuse large B-cell lymphoma: a retrospective study in 337 patients treated by chemotherapy with or without rituximab. Ann Oncol 2011; 22: 1601–7.
36. Nam SJ, Go H, Paik JH. An increase of M2 macrophages predicts poor prognosis in patients with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. Leukemia Lymphoma 2014; 55 (11): 2466–76.
37. Ok CJ, Xu-Monette ZY, Tzankov A. STAT3 expression and clinical inplications in de novo diffuse large B cell lymphoma: a report from the International DLBCL Rituximab-CHOP consortium program. Blood 2013; 122 (21). https://ash.confex.com/ash/2013/webprogram/Paper60938.html.
38. Ok CY, Chen J, Xu-Monette Z. Clinical implications of phosphorylated STAT3 expression in de novo diffuse large B-cell lymphoma. Clinical Cancer Res 2014; 20 (19): 5113–23.
39. Tzankov A, Xu-Monette Z, Gerhard M. Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP. Modern Pathol 2014; 27: 958–71.
40. Valera A, Colomo L, Martinez A. ALK-positive large B-cell lymphomas express a terminal B-cell differentiation program and activated STAT3 but lack MYC rearrangements. Modern Pathol 2013; 26: 1329–37.
41. Visco C, Tzankov A, Xu-Monette Z. Patients with diffuse large B-cell lymphoma of germinal center origin with BCL2 translocations have poor outcome, irrespective of MYC status: a report from an International DLBCL rituximab-CHOP consortium program study. Haematologica 2013; 98 (2): 255–63.
42. Wu ZL, Song YQ, Shi YF. High nuclear expression of STAT3 is associated with unfavorable prognosis in diffuse large B-cell lymphoma. J Hematol Oncol 2011; 4 (31). http://www.jhoonline.org/content/pdf/1756-8722-4-31.pdf
43. Xie M, Wei Y, Ley Y. The prognostic significance of tumor-associated macrophages and NK cells in patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood 2014; 124 (21). http://www.bloodjournal.org/content/124/21/5390.full.pdf
44. Yamamoto W, Nakamura N, Tomita N. Human leukocyte antigen – DR expression on flow cytometry and tumor associated macrophages in diffuse large B cell lymphoma treated by: rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone therapy: retrospective cogort study. Leukemia/Lymphoma 2014; 55 (12): 2721–7.
45. Imbach P, Kuhne Th, Arceci R. Pediatric Oncology. A comprehensive guide. 2006; p. 61–9.
46. Rosolen A, Perkins SL, Pinkerton CR. Revised International Pediatric Non-Hodgkin Lymphoma Staging System. J Clin Oncol 2015; 33 (18): 2106–11.
47. Apostolopoulos DJ, Papandrianos NI, Symeonidis A. Technetium-99m depreotide imaging by single photon emission tomography/low resolution computed tomography in malignant lymphomas: comparison with gallium-67 citrate. Ann Nuclear Med 2010; 24: 639–47.
48. Bardi E, Csoka M, Garai I. Value of FDG-PET/CT examinations in different cancers of children, focusing on lymphomas. Pathol Oncol Res 2014; 20: 139–43.
49. Dabaja B, Phan J, Mawlawi O. Clinical implications of PET-negative residual CT masses after chemotherapy for diffuse large B-cell lymphoma. Leukemia Lymphoma 2013; 54 (12): 2631–8.
50. Furth C, Steffen IG, Erdrich AS. Explorative analyses on the value of interim PET for prediction of response in pediatric and adolescent non-Hodgkin lymphoma patients. EJNMMI res 2013; 3 (71). http://www.ejnmmires.com /content/3/1/71
51. Lange J, Burghardt B. Treatment of adolescents with aggressive B-cell malignancies: the pediatric experience. Curr Hematol Malign Rep 2013; 8 (3): 226–35.
52. Scott R, Jo-Anne V, Aliakbar S. Characteristic expression patterns of TCL1, CD38, CD44 identify aggressive lymphomas harboring a MYC translocation. Am J Surg Pathol 2008; 32 (1): 113–22.
53. Green TM, Nielsen O, de Stricker K. High levels of nuclear MYC protein predict the presence of MYC rearrangement in diffuse large B-cell lymphoma. Am J Surg Pathol 2012; 36 (4): 612–9.
54. Kondratieva S, Duraisamy S, Unitt CL. Aberrant expression of the dendritic cell marker TNFAIP2 by the malignant cells of Hodgkin lymphoma and primary mediastinal large B-cell lymphoma distinguishes these tumor types from morphologically and phenotypically similar lymphomas. Am J Surg Pathol 2011; 35 (10): 1531–9.
55. Togunaga T, Tomita A, Sugimoto K. De novo diffuse large B-cell lymphoma with a CD20 immunohistochemistry-positive and flow cytometry-negative phenotype: molecular mechanisms and correlation with rituximab sensitivity. Cancer Sci 2014; 105 (1): 35–43.
56. Song G, Cho WC, Gu L. Increased CD59 protein expression is associated with the outcome of patients with diffuse large B-cell lymphoma treated with R-CHOP. Med Oncol 2014; 31 (56). http://link.springer.com.sci-hub.org/article/10.1007/s12032-014-0056-y
57. Fen Liu, Ding H, Jin X. FCGR3A 158 V/F polymorphism and response to frontline R-CHOP therapy in diffuse large B-cell lymphoma. DNA Cell Biol 2014; 33: 616–23.
58. Morschhauser FA, Cartron G, Thieblemont C. Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large B-cell lymphoma or mantle-cell lymphoma: results from the Phase II GAUGUIN study. J Clin Oncol 2013; 31: 2912–9.
59. Coiffier B, Radford J, Bosly A. A multicentre, phase II trial ofatumumab monotherapy in relapsed/progressive diffuse large B-cell lymphoma. Br J Hematol 2013; 163: 334–42.
60. Viardot A, Goebeler M, Hess G. Treatment of relapsed/refractory diffuse large B cell lymphoma with the bispecific T-cell engager (BiTE) antibody construct blinatumomab: primary analysis results from an open-label, phase II study. ASH annual meeting abstracts book. 2014; 4460. https://ash.confex.com/ ash/2014/webprogram/Paper 68589. html
61. Portell CA, Wenzell CM, Advani AS. Clinical and pharmacologic aspects of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia. Clin Pharmacol Adv Appl 2013; 5: 5–11.
62. Schlegel P, Lang P, Zugmaier G. Pediatric posttransplant relapsed/refractory B-precursor acute lymphoblastic leukemia shows durable remission by therapy with the T-cell engaging bispecific antibody blinatumomab. Haematologica 2014; 99 (7): 1212–8.
63. Stackelberg A, Locatelli F, Zugmaier G. Phase 1/2 study in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) receiving blinatumomab treatment. ASH annual meeting abstracts book. 2014; 2292. https://ash.confex. com/ash/ 2014/webprogram/Paper69576.html
64. Schuster FR, Stanglmaier M, Woessmann W. Immunotherapy with trifunctional anti-CD20 x anti-CD3 antibody FBTA05 (Lymphomun) in pediatric high-risk patients with recurrent CD20-positive B-cell malignancies. Br J Haematol 2015; 169 (1): 90–102.
65. Kochenderfer JN, Dudley ME, Kassim SH. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T-cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol 2014. http://jco.ascopubs.org/content/early/2014/08/25/JCO. 2014.56.2025. full.pdf
66. Wang Y, Zhang WY, Han QW. Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells. Clin Immunol 2014; 155: 160–75.
67. Maude SL, Teachey DT, Porter DA. Chimeric antigen receptor (CAR) modified N cells induce durable remissions in children with relapsed/refractory ALL. Blood 2015; 125 (26): 4017–23.
2. Burkhardt В, Oschlies I, Klapper W. Non-Hodgkin’s lymphoma in adolescents: experiences in 378 adolescent NHL patients treated according to pediatric NHL-BFM protocols. Leukemia. 2011; 25: 153–60.
3. Ковригина А.М., Пробатова Н.А. Лимфома Ходжкина и крупноклеточные лимфомы. М.: Медицинское информационное агентство, 2007; с. 212. / Kovrigina A.M., Probatova N.A. Limfoma Khodzhkina i krupnokletochnye limfomy. M.: Meditsinskoe informatsionnoe agentstvo, 2007; s. 212. [in Russian]
4. Swerdlow SH, Campo E, Harris NL. WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues, Fourth edition. 2008.
5. Reiter A, Klapper W. Recent advances in the understanding and management of diffuse large B-cell lymphoma in children. Br J Hematol 2008; 142: 329–47.
6. Jaffe ES, Pittaluga S. Aggressive B-cell lymphomas: a review of new and old entities in the WHO classification. Hematology 2011; p. 506–14.
7. Heerema NA, Bernheim AB, Lim MS. Meeting report, State of the art and future needs in cytogenetic/molecular genetics/arrays in childhood lymphoma: summary report of workshop at the first international symposium on childhood and adolescent non-Hodgkin lymphoma. Ped Blood Cancer 2005; 45: 616–22.
8. Oschlies I, Klapper W, Zimmermann M. Diffuse large B-cell lymphoma in pediatric patients belongs predominantly to the germinal-center type B-cell lymphomas: a clinicopathologic analysis of cases included in the German BFM (Berlin-Francfurt-Munster) multicenter trial. Blood 2006; 107 (10): 4047–52.
9. Miles R, Raphael M, McCarthy K. Pediatric diffuse large B-cell lymphoma demonstrates a high proliferation index, frequent c-myc protein expression, and a high incidence of germinal center subtype: report of the French-American-British (FAB) International Study Group. Ped Blood Cancer 2008; 51 (3): 369–74.
10. Roschewski M, Staudt LM, Wilson WH. Diffuse large B-cell lymphoma – treatment approaches in the molecular era. Nat Rev Clin Oncol 2014; 11 (1): 12–23.
11. Schneider C, Pasqualucci L, Dalla-Favera R. Molecular pathogenesis of diffuse large B-cell lymphoma. Semin Diagn Pathol 2011; 28: 167–77.
12. Барышников А.Ю., Валиев Т.Т., Губин А.Н. Лимфомы у детей: практическое руководство. Под ред. Г.Л.Менткевича, С.А.Маяковой. М.: Практическая медицина, 2014. / Baryshnikov A.Iu., Valiev T.T., Gubin A.N. Limfomy u detei: prakticheskoe rukovodstvo. Pod red. G.L.Mentkevicha, S.A.Maiakovoi. M.: Prakticheskaia meditsina, 2014. [in Russian]
13. Менткевич Г.Л., Маякова С.А. Лимфомы у детей. М.: Практическая медицина, 2014. / Mentkevich G.L., Maiakova S.A. Limfomy u detei. M.: Prakticheskaia meditsina, 2014. [in Russian]
14. Laver JH, Kraveka JM, Hutchison RE. Advanced-Stage Large-Cell Lymphoma in Children and Adolescents: Results of a Randomized Trial Incorporating intermediate-Dose Methotrexate and High-Dose Cytarabine in the Maintenance Phase of the APO Regimen: A Pediatric Oncology Group Phase III Trial. J Clin Oncol 2005; 23 (3): 541–7.
15. Tsurusawa M, Mori T, Kikuchi A. Improved treatment results of Children with B-cell non-Hodgkin lymphoma: a report from Japanese pediatric leukemia/lymphoma study group B-NHL03 study. Ped Blood Cancer 2014; 61: 1215–21.
16. Goldman S, Smith L, Anderson JR. Rituximab and FAB/LMB96 chemotherapy in children with stage III/IV B-cell non-Hodgkin lymphoma: a Children’s Oncology group report. Leukemia 2013; 27: 1174–7.
17. Barth MJ, Goldman S, Smith L. Rituximab pharmacokinetics in children and adolescents with de novo intermediate and advanced mature B-cell lymphoma/leukemia: a Children’s Oncology group report. Br J Haematol 2013; 162: 678–83.
18. Самочатова Е.В., Шелихова Л.Н., Мякова Н.В. Возможности и проблемы современной терапии неходжкинских лимфом у детей и подростков. Педиатрия. 2011; 90 (4): 37–43. / Samochatova E.V., Shelikhova L.N., Miakova N.V. Vozmozhnosti i problemy sovremennoi terapii nekhodzhkinskikh limfom u detei i podrostkov. Pediatriia. 2011; 90 (4): 37–43. [in Russian]
19. Самочатова Е.В., Шелихова Л.Н., Белогурова М.Б. Комбинированная химиоиммунотерапия больных неходжкинскими лимфомами из зрелых В-клеток возрастной группы до 18 лет: результаты многоцентрового исследования НХЛ2004м с применением ритуксимаба и модифицированного протокола Б-НХЛ БФМ 90. Онкогематология. 2009; 3: 4–14. / Samochatova E.V., Shelikhova L.N., Belogurova M.B. Kombinirovannaia khimioimmunoterapiia bol'nykh nekhodzhkinskimi limfomami iz zrelykh V-kletok vozrastnoi gruppy do 18 let: rezul'taty mnogotsentrovogo issledovaniia NKhL2004m s primeneniem rituksimaba i modifitsirovannogo protokola B-NKhL BFM 90. Onkogematologiia. 2009; 3: 4–14. [in Russian]
20. Самочатова Е.В., Шелихова Л.Н., Мякова Н.В. Лечение диффузной Б-крупноклеточной лимфомы у детей с применением интенсивной химиотерапии с ритуксимабом: предварительные результаты. Детская онкология. 2007; 3–4: 51–6. / Samochatova E.V., Shelikhova L.N., Miakova N.V. Lechenie diffuznoi B-krupnokletochnoi limfomy u detei s primeneniem intensivnoi khimioterapii s rituksimabom: predvaritel'nye rezul'taty. Detskaia onkologiia. 2007; 3–4: 51–6. [in Russian]
21. Klapper W, Kreuz M, Kohler CW. Patient age at diagnosis is associated with the molecular characteristics of diffuse large B-cell lymphoma. Blood 2012; 119 (8): 1882–7.
22. Chen Y, Sun XF, Cai RQ. Germinal-center type B-cell classification and clinical characteristics of Chinese pediatric diffuse large B-cell lymphoma: a report of 76 cases. Chin J Cancer 2013; 32 (10): 561–6.
23. Poirel HA, Cairo MS, Heerema NA. Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell non-Hodgkin’s lymphoma: results of the FAB/LMB 96 international study. Leukemia 2009; 23 (2): 323–31.
24. Reiter A, Schrappe M, Tieman M. Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy: a report of the Berlin-Frankfurt-Munster group Trial NHL-BFM90. Blood 1999; 94 (10): 3294–306.
25. Woessmann W, Seidemann K, Mann G, Zimmermann M. The impact of the methotrexate administration schedule and dose in the treatment of children and adolescents with B-cell neoplasms: a report of the BFM group study NHL-BFM95. Blood 2005; 105: 948–58.
26. Meyer PN, Fu K, Greiner TG. Immunohistochemical methods for predicting cell of origin and survival in patients with diffuse large B-cell lymphoma treated with rituximab. J Clin Oncol 2011; 29 (2): 200–7.
27. Perry AM, Zdravko M. Biological prognostic markers in diffuse large B-cell lymphoma. Cancer Control 2012; 19 (3): 214–26.
28. Culpin RE, Sieniawski M, Angus B. Prognostic significance of immunohistochemistry-based markers and algorithms in immunochemotherapy-treated diffuse large B cell lymphoma patients. Histopathology 2013; 63: 788–801.
29. Visco Y, Li Y, Xu-Monette ZY. Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma: a report from the International DLBCL Rituximab-CHOP Consortium Prorram Study. Leukemia 2012; 26 (9): 2103–13.
30. Cox CM, Di Napoli A, Scarpino S. Clinicopathologic characterization of diffuse large B cell lymphoma with an associated serum monoclonal IgM component. PLOS one 2014. http://www.plosone.org/article/fetchObject.action?uri=info:doi/ 10.1371/journal.pone.0093903&representation=PDF
31. Hu S, Xu-Monette ZY, Balasubramanyam A. CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature: a report from the International DLBCL Rituximab-CHOP Consortium Program Study. Blood 2013; 121: 2715–24.
32. Hu S, Xu-Monette ZY, Tzankov A. MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from the international DLBCL Rituximab-CHOP consortium program. Blood 2013; 121 (20): 4021–31.
33. Ichikava S, Fukuhara N, Katsushima H. Association between BACH2 expression and clinical prognosis in diffuse large B cell lymphoma. Cancer Sci 2014; 105 (4): 437–44.
34. Laurent C, Do C, Gascoyne RD. Anaplastic lymphoma kinase – positive diffuse large B-cell lymphoma: a rare clinicopathologic entity with poor prognosis. J Clin Oncol 2009; 27 (25): 4211–6.
35. Miyazaki K, Yamaguchi M, Suzuki R. CD5-positive diffuse large B-cell lymphoma: a retrospective study in 337 patients treated by chemotherapy with or without rituximab. Ann Oncol 2011; 22: 1601–7.
36. Nam SJ, Go H, Paik JH. An increase of M2 macrophages predicts poor prognosis in patients with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. Leukemia Lymphoma 2014; 55 (11): 2466–76.
37. Ok CJ, Xu-Monette ZY, Tzankov A. STAT3 expression and clinical inplications in de novo diffuse large B cell lymphoma: a report from the International DLBCL Rituximab-CHOP consortium program. Blood 2013; 122 (21). https://ash.confex.com/ash/2013/webprogram/Paper60938.html.
38. Ok CY, Chen J, Xu-Monette Z. Clinical implications of phosphorylated STAT3 expression in de novo diffuse large B-cell lymphoma. Clinical Cancer Res 2014; 20 (19): 5113–23.
39. Tzankov A, Xu-Monette Z, Gerhard M. Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP. Modern Pathol 2014; 27: 958–71.
40. Valera A, Colomo L, Martinez A. ALK-positive large B-cell lymphomas express a terminal B-cell differentiation program and activated STAT3 but lack MYC rearrangements. Modern Pathol 2013; 26: 1329–37.
41. Visco C, Tzankov A, Xu-Monette Z. Patients with diffuse large B-cell lymphoma of germinal center origin with BCL2 translocations have poor outcome, irrespective of MYC status: a report from an International DLBCL rituximab-CHOP consortium program study. Haematologica 2013; 98 (2): 255–63.
42. Wu ZL, Song YQ, Shi YF. High nuclear expression of STAT3 is associated with unfavorable prognosis in diffuse large B-cell lymphoma. J Hematol Oncol 2011; 4 (31). http://www.jhoonline.org/content/pdf/1756-8722-4-31.pdf
43. Xie M, Wei Y, Ley Y. The prognostic significance of tumor-associated macrophages and NK cells in patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood 2014; 124 (21). http://www.bloodjournal.org/content/124/21/5390.full.pdf
44. Yamamoto W, Nakamura N, Tomita N. Human leukocyte antigen – DR expression on flow cytometry and tumor associated macrophages in diffuse large B cell lymphoma treated by: rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone therapy: retrospective cogort study. Leukemia/Lymphoma 2014; 55 (12): 2721–7.
45. Imbach P, Kuhne Th, Arceci R. Pediatric Oncology. A comprehensive guide. 2006; p. 61–9.
46. Rosolen A, Perkins SL, Pinkerton CR. Revised International Pediatric Non-Hodgkin Lymphoma Staging System. J Clin Oncol 2015; 33 (18): 2106–11.
47. Apostolopoulos DJ, Papandrianos NI, Symeonidis A. Technetium-99m depreotide imaging by single photon emission tomography/low resolution computed tomography in malignant lymphomas: comparison with gallium-67 citrate. Ann Nuclear Med 2010; 24: 639–47.
48. Bardi E, Csoka M, Garai I. Value of FDG-PET/CT examinations in different cancers of children, focusing on lymphomas. Pathol Oncol Res 2014; 20: 139–43.
49. Dabaja B, Phan J, Mawlawi O. Clinical implications of PET-negative residual CT masses after chemotherapy for diffuse large B-cell lymphoma. Leukemia Lymphoma 2013; 54 (12): 2631–8.
50. Furth C, Steffen IG, Erdrich AS. Explorative analyses on the value of interim PET for prediction of response in pediatric and adolescent non-Hodgkin lymphoma patients. EJNMMI res 2013; 3 (71). http://www.ejnmmires.com /content/3/1/71
51. Lange J, Burghardt B. Treatment of adolescents with aggressive B-cell malignancies: the pediatric experience. Curr Hematol Malign Rep 2013; 8 (3): 226–35.
52. Scott R, Jo-Anne V, Aliakbar S. Characteristic expression patterns of TCL1, CD38, CD44 identify aggressive lymphomas harboring a MYC translocation. Am J Surg Pathol 2008; 32 (1): 113–22.
53. Green TM, Nielsen O, de Stricker K. High levels of nuclear MYC protein predict the presence of MYC rearrangement in diffuse large B-cell lymphoma. Am J Surg Pathol 2012; 36 (4): 612–9.
54. Kondratieva S, Duraisamy S, Unitt CL. Aberrant expression of the dendritic cell marker TNFAIP2 by the malignant cells of Hodgkin lymphoma and primary mediastinal large B-cell lymphoma distinguishes these tumor types from morphologically and phenotypically similar lymphomas. Am J Surg Pathol 2011; 35 (10): 1531–9.
55. Togunaga T, Tomita A, Sugimoto K. De novo diffuse large B-cell lymphoma with a CD20 immunohistochemistry-positive and flow cytometry-negative phenotype: molecular mechanisms and correlation with rituximab sensitivity. Cancer Sci 2014; 105 (1): 35–43.
56. Song G, Cho WC, Gu L. Increased CD59 protein expression is associated with the outcome of patients with diffuse large B-cell lymphoma treated with R-CHOP. Med Oncol 2014; 31 (56). http://link.springer.com.sci-hub.org/article/10.1007/s12032-014-0056-y
57. Fen Liu, Ding H, Jin X. FCGR3A 158 V/F polymorphism and response to frontline R-CHOP therapy in diffuse large B-cell lymphoma. DNA Cell Biol 2014; 33: 616–23.
58. Morschhauser FA, Cartron G, Thieblemont C. Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large B-cell lymphoma or mantle-cell lymphoma: results from the Phase II GAUGUIN study. J Clin Oncol 2013; 31: 2912–9.
59. Coiffier B, Radford J, Bosly A. A multicentre, phase II trial ofatumumab monotherapy in relapsed/progressive diffuse large B-cell lymphoma. Br J Hematol 2013; 163: 334–42.
60. Viardot A, Goebeler M, Hess G. Treatment of relapsed/refractory diffuse large B cell lymphoma with the bispecific T-cell engager (BiTE) antibody construct blinatumomab: primary analysis results from an open-label, phase II study. ASH annual meeting abstracts book. 2014; 4460. https://ash.confex.com/ ash/2014/webprogram/Paper 68589. html
61. Portell CA, Wenzell CM, Advani AS. Clinical and pharmacologic aspects of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia. Clin Pharmacol Adv Appl 2013; 5: 5–11.
62. Schlegel P, Lang P, Zugmaier G. Pediatric posttransplant relapsed/refractory B-precursor acute lymphoblastic leukemia shows durable remission by therapy with the T-cell engaging bispecific antibody blinatumomab. Haematologica 2014; 99 (7): 1212–8.
63. Stackelberg A, Locatelli F, Zugmaier G. Phase 1/2 study in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) receiving blinatumomab treatment. ASH annual meeting abstracts book. 2014; 2292. https://ash.confex. com/ash/ 2014/webprogram/Paper69576.html
64. Schuster FR, Stanglmaier M, Woessmann W. Immunotherapy with trifunctional anti-CD20 x anti-CD3 antibody FBTA05 (Lymphomun) in pediatric high-risk patients with recurrent CD20-positive B-cell malignancies. Br J Haematol 2015; 169 (1): 90–102.
65. Kochenderfer JN, Dudley ME, Kassim SH. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T-cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol 2014. http://jco.ascopubs.org/content/early/2014/08/25/JCO. 2014.56.2025. full.pdf
66. Wang Y, Zhang WY, Han QW. Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells. Clin Immunol 2014; 155: 160–75.
67. Maude SL, Teachey DT, Porter DA. Chimeric antigen receptor (CAR) modified N cells induce durable remissions in children with relapsed/refractory ALL. Blood 2015; 125 (26): 4017–23.
________________________________________________
2. Burkhardt В, Oschlies I, Klapper W. Non-Hodgkin’s lymphoma in adolescents: experiences in 378 adolescent NHL patients treated according to pediatric NHL-BFM protocols. Leukemia. 2011; 25: 153–60.
3. Kovrigina A.M., Probatova N.A. Limfoma Khodzhkina i krupnokletochnye limfomy. M.: Meditsinskoe informatsionnoe agentstvo, 2007; s. 212. [in Russian]
4. Swerdlow SH, Campo E, Harris NL. WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues, Fourth edition. 2008.
5. Reiter A, Klapper W. Recent advances in the understanding and management of diffuse large B-cell lymphoma in children. Br J Hematol 2008; 142: 329–47.
6. Jaffe ES, Pittaluga S. Aggressive B-cell lymphomas: a review of new and old entities in the WHO classification. Hematology 2011; p. 506–14.
7. Heerema NA, Bernheim AB, Lim MS. Meeting report, State of the art and future needs in cytogenetic/molecular genetics/arrays in childhood lymphoma: summary report of workshop at the first international symposium on childhood and adolescent non-Hodgkin lymphoma. Ped Blood Cancer 2005; 45: 616–22.
8. Oschlies I, Klapper W, Zimmermann M. Diffuse large B-cell lymphoma in pediatric patients belongs predominantly to the germinal-center type B-cell lymphomas: a clinicopathologic analysis of cases included in the German BFM (Berlin-Francfurt-Munster) multicenter trial. Blood 2006; 107 (10): 4047–52.
9. Miles R, Raphael M, McCarthy K. Pediatric diffuse large B-cell lymphoma demonstrates a high proliferation index, frequent c-myc protein expression, and a high incidence of germinal center subtype: report of the French-American-British (FAB) International Study Group. Ped Blood Cancer 2008; 51 (3): 369–74.
10. Roschewski M, Staudt LM, Wilson WH. Diffuse large B-cell lymphoma – treatment approaches in the molecular era. Nat Rev Clin Oncol 2014; 11 (1): 12–23.
11. Schneider C, Pasqualucci L, Dalla-Favera R. Molecular pathogenesis of diffuse large B-cell lymphoma. Semin Diagn Pathol 2011; 28: 167–77.
12. Baryshnikov A.Iu., Valiev T.T., Gubin A.N. Limfomy u detei: prakticheskoe rukovodstvo. Pod red. G.L.Mentkevicha, S.A.Maiakovoi. M.: Prakticheskaia meditsina, 2014. [in Russian]
13. Mentkevich G.L., Maiakova S.A. Limfomy u detei. M.: Prakticheskaia meditsina, 2014. [in Russian]
14. Laver JH, Kraveka JM, Hutchison RE. Advanced-Stage Large-Cell Lymphoma in Children and Adolescents: Results of a Randomized Trial Incorporating intermediate-Dose Methotrexate and High-Dose Cytarabine in the Maintenance Phase of the APO Regimen: A Pediatric Oncology Group Phase III Trial. J Clin Oncol 2005; 23 (3): 541–7.
15. Tsurusawa M, Mori T, Kikuchi A. Improved treatment results of Children with B-cell non-Hodgkin lymphoma: a report from Japanese pediatric leukemia/lymphoma study group B-NHL03 study. Ped Blood Cancer 2014; 61: 1215–21.
16. Goldman S, Smith L, Anderson JR. Rituximab and FAB/LMB96 chemotherapy in children with stage III/IV B-cell non-Hodgkin lymphoma: a Children’s Oncology group report. Leukemia 2013; 27: 1174–7.
17. Barth MJ, Goldman S, Smith L. Rituximab pharmacokinetics in children and adolescents with de novo intermediate and advanced mature B-cell lymphoma/leukemia: a Children’s Oncology group report. Br J Haematol 2013; 162: 678–83.
18. Samochatova E.V., Shelikhova L.N., Miakova N.V. Vozmozhnosti i problemy sovremennoi terapii nekhodzhkinskikh limfom u detei i podrostkov. Pediatriia. 2011; 90 (4): 37–43. [in Russian]
19. Samochatova E.V., Shelikhova L.N., Belogurova M.B. Kombinirovannaia khimioimmunoterapiia bol'nykh nekhodzhkinskimi limfomami iz zrelykh V-kletok vozrastnoi gruppy do 18 let: rezul'taty mnogotsentrovogo issledovaniia NKhL2004m s primeneniem rituksimaba i modifitsirovannogo protokola B-NKhL BFM 90. Onkogematologiia. 2009; 3: 4–14. [in Russian]
20. Samochatova E.V., Shelikhova L.N., Miakova N.V. Lechenie diffuznoi B-krupnokletochnoi limfomy u detei s primeneniem intensivnoi khimioterapii s rituksimabom: predvaritel'nye rezul'taty. Detskaia onkologiia. 2007; 3–4: 51–6. [in Russian]
21. Klapper W, Kreuz M, Kohler CW. Patient age at diagnosis is associated with the molecular characteristics of diffuse large B-cell lymphoma. Blood 2012; 119 (8): 1882–7.
22. Chen Y, Sun XF, Cai RQ. Germinal-center type B-cell classification and clinical characteristics of Chinese pediatric diffuse large B-cell lymphoma: a report of 76 cases. Chin J Cancer 2013; 32 (10): 561–6.
23. Poirel HA, Cairo MS, Heerema NA. Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell non-Hodgkin’s lymphoma: results of the FAB/LMB 96 international study. Leukemia 2009; 23 (2): 323–31.
24. Reiter A, Schrappe M, Tieman M. Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy: a report of the Berlin-Frankfurt-Munster group Trial NHL-BFM90. Blood 1999; 94 (10): 3294–306.
25. Woessmann W, Seidemann K, Mann G, Zimmermann M. The impact of the methotrexate administration schedule and dose in the treatment of children and adolescents with B-cell neoplasms: a report of the BFM group study NHL-BFM95. Blood 2005; 105: 948–58.
26. Meyer PN, Fu K, Greiner TG. Immunohistochemical methods for predicting cell of origin and survival in patients with diffuse large B-cell lymphoma treated with rituximab. J Clin Oncol 2011; 29 (2): 200–7.
27. Perry AM, Zdravko M. Biological prognostic markers in diffuse large B-cell lymphoma. Cancer Control 2012; 19 (3): 214–26.
28. Culpin RE, Sieniawski M, Angus B. Prognostic significance of immunohistochemistry-based markers and algorithms in immunochemotherapy-treated diffuse large B cell lymphoma patients. Histopathology 2013; 63: 788–801.
29. Visco Y, Li Y, Xu-Monette ZY. Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma: a report from the International DLBCL Rituximab-CHOP Consortium Prorram Study. Leukemia 2012; 26 (9): 2103–13.
30. Cox CM, Di Napoli A, Scarpino S. Clinicopathologic characterization of diffuse large B cell lymphoma with an associated serum monoclonal IgM component. PLOS one 2014. http://www.plosone.org/article/fetchObject.action?uri=info:doi/ 10.1371/journal.pone.0093903&representation=PDF
31. Hu S, Xu-Monette ZY, Balasubramanyam A. CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature: a report from the International DLBCL Rituximab-CHOP Consortium Program Study. Blood 2013; 121: 2715–24.
32. Hu S, Xu-Monette ZY, Tzankov A. MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from the international DLBCL Rituximab-CHOP consortium program. Blood 2013; 121 (20): 4021–31.
33. Ichikava S, Fukuhara N, Katsushima H. Association between BACH2 expression and clinical prognosis in diffuse large B cell lymphoma. Cancer Sci 2014; 105 (4): 437–44.
34. Laurent C, Do C, Gascoyne RD. Anaplastic lymphoma kinase – positive diffuse large B-cell lymphoma: a rare clinicopathologic entity with poor prognosis. J Clin Oncol 2009; 27 (25): 4211–6.
35. Miyazaki K, Yamaguchi M, Suzuki R. CD5-positive diffuse large B-cell lymphoma: a retrospective study in 337 patients treated by chemotherapy with or without rituximab. Ann Oncol 2011; 22: 1601–7.
36. Nam SJ, Go H, Paik JH. An increase of M2 macrophages predicts poor prognosis in patients with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. Leukemia Lymphoma 2014; 55 (11): 2466–76.
37. Ok CJ, Xu-Monette ZY, Tzankov A. STAT3 expression and clinical inplications in de novo diffuse large B cell lymphoma: a report from the International DLBCL Rituximab-CHOP consortium program. Blood 2013; 122 (21). https://ash.confex.com/ash/2013/webprogram/Paper60938.html.
38. Ok CY, Chen J, Xu-Monette Z. Clinical implications of phosphorylated STAT3 expression in de novo diffuse large B-cell lymphoma. Clinical Cancer Res 2014; 20 (19): 5113–23.
39. Tzankov A, Xu-Monette Z, Gerhard M. Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP. Modern Pathol 2014; 27: 958–71.
40. Valera A, Colomo L, Martinez A. ALK-positive large B-cell lymphomas express a terminal B-cell differentiation program and activated STAT3 but lack MYC rearrangements. Modern Pathol 2013; 26: 1329–37.
41. Visco C, Tzankov A, Xu-Monette Z. Patients with diffuse large B-cell lymphoma of germinal center origin with BCL2 translocations have poor outcome, irrespective of MYC status: a report from an International DLBCL rituximab-CHOP consortium program study. Haematologica 2013; 98 (2): 255–63.
42. Wu ZL, Song YQ, Shi YF. High nuclear expression of STAT3 is associated with unfavorable prognosis in diffuse large B-cell lymphoma. J Hematol Oncol 2011; 4 (31). http://www.jhoonline.org/content/pdf/1756-8722-4-31.pdf
43. Xie M, Wei Y, Ley Y. The prognostic significance of tumor-associated macrophages and NK cells in patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood 2014; 124 (21). http://www.bloodjournal.org/content/124/21/5390.full.pdf
44. Yamamoto W, Nakamura N, Tomita N. Human leukocyte antigen – DR expression on flow cytometry and tumor associated macrophages in diffuse large B cell lymphoma treated by: rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone therapy: retrospective cogort study. Leukemia/Lymphoma 2014; 55 (12): 2721–7.
45. Imbach P, Kuhne Th, Arceci R. Pediatric Oncology. A comprehensive guide. 2006; p. 61–9.
46. Rosolen A, Perkins SL, Pinkerton CR. Revised International Pediatric Non-Hodgkin Lymphoma Staging System. J Clin Oncol 2015; 33 (18): 2106–11.
47. Apostolopoulos DJ, Papandrianos NI, Symeonidis A. Technetium-99m depreotide imaging by single photon emission tomography/low resolution computed tomography in malignant lymphomas: comparison with gallium-67 citrate. Ann Nuclear Med 2010; 24: 639–47.
48. Bardi E, Csoka M, Garai I. Value of FDG-PET/CT examinations in different cancers of children, focusing on lymphomas. Pathol Oncol Res 2014; 20: 139–43.
49. Dabaja B, Phan J, Mawlawi O. Clinical implications of PET-negative residual CT masses after chemotherapy for diffuse large B-cell lymphoma. Leukemia Lymphoma 2013; 54 (12): 2631–8.
50. Furth C, Steffen IG, Erdrich AS. Explorative analyses on the value of interim PET for prediction of response in pediatric and adolescent non-Hodgkin lymphoma patients. EJNMMI res 2013; 3 (71). http://www.ejnmmires.com /content/3/1/71
51. Lange J, Burghardt B. Treatment of adolescents with aggressive B-cell malignancies: the pediatric experience. Curr Hematol Malign Rep 2013; 8 (3): 226–35.
52. Scott R, Jo-Anne V, Aliakbar S. Characteristic expression patterns of TCL1, CD38, CD44 identify aggressive lymphomas harboring a MYC translocation. Am J Surg Pathol 2008; 32 (1): 113–22.
53. Green TM, Nielsen O, de Stricker K. High levels of nuclear MYC protein predict the presence of MYC rearrangement in diffuse large B-cell lymphoma. Am J Surg Pathol 2012; 36 (4): 612–9.
54. Kondratieva S, Duraisamy S, Unitt CL. Aberrant expression of the dendritic cell marker TNFAIP2 by the malignant cells of Hodgkin lymphoma and primary mediastinal large B-cell lymphoma distinguishes these tumor types from morphologically and phenotypically similar lymphomas. Am J Surg Pathol 2011; 35 (10): 1531–9.
55. Togunaga T, Tomita A, Sugimoto K. De novo diffuse large B-cell lymphoma with a CD20 immunohistochemistry-positive and flow cytometry-negative phenotype: molecular mechanisms and correlation with rituximab sensitivity. Cancer Sci 2014; 105 (1): 35–43.
56. Song G, Cho WC, Gu L. Increased CD59 protein expression is associated with the outcome of patients with diffuse large B-cell lymphoma treated with R-CHOP. Med Oncol 2014; 31 (56). http://link.springer.com.sci-hub.org/article/10.1007/s12032-014-0056-y
57. Fen Liu, Ding H, Jin X. FCGR3A 158 V/F polymorphism and response to frontline R-CHOP therapy in diffuse large B-cell lymphoma. DNA Cell Biol 2014; 33: 616–23.
58. Morschhauser FA, Cartron G, Thieblemont C. Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large B-cell lymphoma or mantle-cell lymphoma: results from the Phase II GAUGUIN study. J Clin Oncol 2013; 31: 2912–9.
59. Coiffier B, Radford J, Bosly A. A multicentre, phase II trial ofatumumab monotherapy in relapsed/progressive diffuse large B-cell lymphoma. Br J Hematol 2013; 163: 334–42.
60. Viardot A, Goebeler M, Hess G. Treatment of relapsed/refractory diffuse large B cell lymphoma with the bispecific T-cell engager (BiTE) antibody construct blinatumomab: primary analysis results from an open-label, phase II study. ASH annual meeting abstracts book. 2014; 4460. https://ash.confex.com/ ash/2014/webprogram/Paper 68589. html
61. Portell CA, Wenzell CM, Advani AS. Clinical and pharmacologic aspects of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia. Clin Pharmacol Adv Appl 2013; 5: 5–11.
62. Schlegel P, Lang P, Zugmaier G. Pediatric posttransplant relapsed/refractory B-precursor acute lymphoblastic leukemia shows durable remission by therapy with the T-cell engaging bispecific antibody blinatumomab. Haematologica 2014; 99 (7): 1212–8.
63. Stackelberg A, Locatelli F, Zugmaier G. Phase 1/2 study in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) receiving blinatumomab treatment. ASH annual meeting abstracts book. 2014; 2292. https://ash.confex. com/ash/ 2014/webprogram/Paper69576.html
64. Schuster FR, Stanglmaier M, Woessmann W. Immunotherapy with trifunctional anti-CD20 x anti-CD3 antibody FBTA05 (Lymphomun) in pediatric high-risk patients with recurrent CD20-positive B-cell malignancies. Br J Haematol 2015; 169 (1): 90–102.
65. Kochenderfer JN, Dudley ME, Kassim SH. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T-cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol 2014. http://jco.ascopubs.org/content/early/2014/08/25/JCO. 2014.56.2025. full.pdf
66. Wang Y, Zhang WY, Han QW. Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells. Clin Immunol 2014; 155: 160–75.
67. Maude SL, Teachey DT, Porter DA. Chimeric antigen receptor (CAR) modified N cells induce durable remissions in children with relapsed/refractory ALL. Blood 2015; 125 (26): 4017–23.
Авторы
А.С.Левашов*1, А.М.Ковригина2, Т.Т.Валиев1, Е.С.Беляева1, А.В.Попа1, Г.Л.Менткевич1
1 ФГБУ Российский онкологический научный центр им. Н.Н.Блохина Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23;
2 ФГБУ Гематологический научный центр Минздрава России. 125167, Россия, Москва, Новый Зыковский пр., д. 4
*andreyslevashov@mail.ru
1 Pediatric Oncology and Hematology Research Institute of N.N.Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23;
2 National Research Center for Hematology of the Ministry of Health of the Russian Federation. 125167, Russian Federation, Moscow, Novyi Zykovskii pr., d. 4
*andreyslevashov@mail.ru
1 ФГБУ Российский онкологический научный центр им. Н.Н.Блохина Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23;
2 ФГБУ Гематологический научный центр Минздрава России. 125167, Россия, Москва, Новый Зыковский пр., д. 4
*andreyslevashov@mail.ru
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1 Pediatric Oncology and Hematology Research Institute of N.N.Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23;
2 National Research Center for Hematology of the Ministry of Health of the Russian Federation. 125167, Russian Federation, Moscow, Novyi Zykovskii pr., d. 4
*andreyslevashov@mail.ru
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