Therapy for Burkitt’s lymphoma according to the BL-M-04 protocol: 12-year experience


Aim. To evaluate the efficiency and toxicity of the intensive Burkitt’s lymphoma (BL) therapy protocol BL-M-04. Subjects and methods. A total of 70 patients diagnosed with BL, including 45 men and 25 women whose age was 15 to 62 years (median age 31 years), were followed up in 2003 to 2014. Stage I (according to S. Murphy) was diagnosed in 4 (5.7%) patients; II in 9 (12.9%), III in 25 (35.7%), IV in 11 (15.7%), and Burkitt’s leukemia in 21 (30%). There were tumor involvements of the bone marrow and central nervous system in 23 (32.9%) and 15 (21.4%) patients, respectively. B symptoms were detected in 56 (80%) patients; enhanced lactate dehydrogenase (LDH) activity was found in 50 (78.1%) out of 64 patients; moreover, in 34 (56.2%) out of 64 patients, LDH activity was more than twice as high as the reference values. The median LDH activity was 2398 (238-20,300) U/l. Acute renal failure at disease onset was identified in 17 (24.2%) patients; chemotherapy was initiated in 8 patients during renal replacement therapy. The treatment was performed using the BL-M-04±R protocol (4 successive blocks of A-C-A-C±R). Six blocks of A-C-A-C-A-C with rituximab has been carried out in patients with bone marrow involvement since 2011. Results. Sixty-two (89%) patients achieved complete remission. At this time, 6 patients died from therapy complications during remission induction; 2 patients were observed to have disease progression; 3 developed disease recurrence (2 patients had early recurrence; 1 patient developed recurrence 2 years after treatment). Five-year overall survival (OS) was 85%; 5-year relapse-free survival (RFS) was 95%. The Cox multivariate regression analysis revealed that Burkitt’s leukemia and bone marrow involvement were independent factors that influenced OS and RFS. The poor somatic status (3—4 ECOC scores versus 0—2 scores) proved to be statistically significant for OS rather than RFS. Conclusion. Despite the optimistic results obtained by our study group, there is a need to further improve BL treatment protocols and to elaborate novel approaches to therapy particularly for older patients and patients with Burkitt’s leukemia.


  1. Leoncini L, Raphael M, Stein H, Harris NL, Jaffe ES, Kluin PM. Burkitt Lymphoma in WHO Classification of tumors of haematopoietic and lymphoid tissues. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, eds. International Agency for Research on Cancer. Lyon; 2008;265-266.
  2. Барях Е.А., Кравченко С.К., Обухова Т.Н., Звонков Е.Е., Кременецкая А.М., Клясова Г.А., Терехова А.Ю., Воробьев А.И. Лимфома Беркитта: клиника, диагностика, лечение. Клиническая онкогематология. Фундаментальные исследования и клиническая практика. 2009;2(2):137-146.
  3. Барях Е.А., Кравченко С.К., Кременецкая А.М., Звонков Е.Е., Магомедова А.У., Обухова Т.Н., Попова Ю.Ю., Финк О.С., Клясова Г.А., Шулутко Е.М., Галстян Г.М., Капланская И.В., Воробьев И.А., Воробьев А.И. Лейкоз/лимфома Беркитта: клинические особенности, диагностические критерии, терапевтическая тактика. Клиническая онкогематология. Фундаментальные исследования и клиническая практика. 2010;3(2):138-143.
  4. Барях Е.А., Кравченко С.К. Протокол терапии лимфомы Беркитта взрослых по программе Лб-М-04. Сборник алгоритмов диагностики и протоколов лечения заболеваний системы крови. Под ред. Савченко В.Г. М; 2012:719-734.
  5. Обухова Т.Н., Барях Е.А., Капланская И.Б., Домрачева Е.В., Кравченко С.К. Выявление диагностических для лимфомы Беркитта транслокаций методом флюоресцентной in situ гибридизации на гистологических срезах парафиновых блоков. Терапевтический архив. 2007;79(7):80-83.
  6. Финк О.С., Барях Е.А., Кравченко С.К., Фоломеев В.Н. Тактика терапии лимфомы Беркитта с вовлечением миндалины и угрозой асфиксии. Гематология и трансфузиология. 2009;54(3):28-30.
  7. Common Terminology Criteria for Adverse Events (CTCAE), version 4, published: May 28, 2009. US Department of Health and Human Services, National Institutes of Health, National Cancer Institute.
  8. Кравченко С.К., Барях Е.А., Замятина В.И., Пересторонина Т.Н., Финк О.С., Губкин А.В., Егорова Е.К., Звонков Е.Е., Илюшкина Е.А., Красильникова Б.Б., Морозова А.К., Воробьев И.А., Капланская И.Б., Клясова Г.А., Обухова Т.Н., Кременецкая А.М., Воробьев А.И. Высокодозная терапия лимфомы Беркитта у больных старше 40 лет. Терапевтический архив. 2008;80(7):9-18.
  9. Bernstein JI, Coleman CN, Strickler JG, Dorfman RF, Rosenberg SA. Combined modality therapy for adults with small noncleaved cell lymphoma (Burkitt‘s and non-Burkitt‘s types). J Clin Oncol. 1986;4(6):847-858.
  10. Lopez JM, Hagemeister FB, MgLaughlin P, Velasquez WS, Swan F, Redman JR, Rodriguez MA, Tucker SL, Silvermintz K, Johnson J. Small noncleaved cell lymphoma in adult: superior results for stage I—III disease. J Clin Oncol. 1990;8(4):615-622.
  11. McMaster ML, Greer JP, Greco FA, Johnson DH, Wolff SN, Hainsworth JD. Effective treatment of small-noncleaved-cell lymphoma with high-intensity, brief-duration chemotherapy. J Clin Oncol. 1991;9(6):941-946.
  12. Longo D, Duffey P, Jaffe E, Raffeld M, Hubbard SM, Fisher RI, Wittes RE, DeVita VT Jr, Young RC. Diffuse small noncleaved-cell, non Burkitt’s lymphoma in adults: a high-grade lymphoma responsive to ProMACE-based combination therapy. J Clin Oncol. 1994;12:2153-2159.
  13. Diviné M, Lepage E, Brière J, Pautier P, Dupriez B, Lederlin P, Mineur P, Tilly H, Blanc M, Audhuy B, Herbrecht R, Coiffier B, Reyes F. Is the small non-cleaved-cell lymphoma histologic subtype a poor prognostic factor in adult patients? A case-controlled analysis. The Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol. 1996;14(1):240-248.
  14. Soussain C, Patte C, Ostronoff M, Delmer A, Rigal-Huguet F, Cambier N, Leprisé PY, François S, Cony-Makhoul P, Harousseau JL. Small noncleaved cell lymphoma and leukemia in adults. A retrospective study of 65 adults treated with the LMB pediatric protocols. Blood. 1995;85(3):664-674.
  15. Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005;16(12):1928-1935.
  16. Hoelzer D, Ludwig WD, Thiel E, Gassmann W, Löffler H, Fonatsch C, Rieder H, Heil G, Heinze B, Arnold R, Hossfeld D, Büchner T, Koch P, Freund M, Hiddemann W, Maschmeyer G, Heyll A, Aul C, Faak T, Kuse R, Ittel TH, Gramatzki M, Diedrich H, Kolbe K, Fuhr HG, Fischer K, Schadeck-Gressel C, Weiss A, Strohscheer I, Metzner B, Fabry U, Gökbuget N, Völkers B, Messerer D, Uberla K. Improved outcome in adult B-cell acute lymphoblastic leukemia. Blood. 1996;87(2):495-508.
  17. Magrath I, Adde M, Shad A, Venzon D, Seibel N, Gootenberg J, Neely J, Arndt C, Nieder M, Jaffe E, Wittes RA, Horak I.D. Adult and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen. J Clin Oncol. 1996;14(3):925-934.
  18. Mead GM, Sydes MR, Walewski J, Grigg A, Hatton CS, Pescosta N, Guarnaccia C, Lewis MS, McKendrick J, Stenning SP, Wright D. An international evaluation of CODOX-M and CODOX-M alternating with IVAC in adult Burkitt’s lymphoma: results of United Kingdom Lymphoma Group LY06 study. Ann Oncol. 2002;13(8):1264-1274.
  19. Thomas DA, Cortes J, O’Brien S, Pierce S, Faderl S, Albitar M, Hagemeister FB, Cabanillas FF, Murphy S, Keating MJ, Kantarjian H. Hyper-CVAD program in Burkitt’s-type adult acute lymphoblastic leukemia. J Clin Oncol. 1999;17(8):2461-2470.
  20. Lee EJ, Petroni GR, Schiffer CA, Freter CE, Johnson JL, Barcos M, Frizzera G, Bloomfield CD, Peterson BA. Brief-duration high-intensity chemotherapy for patients with small noncleaved-cell lymphoma or FAB L3 acute lymphocytic leukemia: results of cancer and leukemia group B study 9251. J Clin Oncol. 2001;19(20):4014-4022.
  21. Mead GM, Barrans SL, Qian W, Walewski J, Radford JA, Wolf M., Clawson SM, Stenning SP, Yule CL, Jack AS. A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic criteria (MRC/NCRI LY10 trial). Blood. 2008;112(6):2248-2260. doi: 10.1182/blood-2008-03-145128.
  22. Fayad L, Thomas D, Romaguera J. Update of the M. D. Anderson Cancer Center experience with hyper-CVAD and rituximab for the treatment of mantle cell and Burkitt-type lymphomas. Clin Lymphoma Myeloma. 2007;8 Suppl 2:S57-62.
  23. Barnes J.A, Lacasce AS, Feng Y, Toomey CE, Neuberg D, Michaelson JS, Hochberg EP, Abramson JS. Evaluation of the addition of rituximab to CODOX-M/IVAC for Burkitt’s lymphoma: a retrospective analysis. Ann Oncol. 2011;22(8):1859-1864. doi: 10.1093/annonc/mdq677.
  24. Intermesoli T, Rambaldi A, Rossi G, Delaini F, Romani C, Pogliani EM, Pagani C, Angelucci E, Terruzzi E, Levis A, Cassibba V, Mattei D, Gianfaldoni G, Scattolin AM, Di Bona E, Oldani E, Parolini M, Gökbuget N, Bassan R. High cure rates in Burkitt lymphoma and leukemia: a Northern Italy Leukemia Group study of the German short intensive rituximab-chemotherapy program. Haematologica. 2013;98(11):1718-1725. doi: 10.3324/haematol.2013.086827.
  25. Dunleavy K, Pittaluga S, Shovlin M, Steinberg SM, Cole D, Grant C, Widemann B, Staudt LM, Jaffe ES, Little RF, Wilson WH. Low-intensity therapy in adults with Burkitt’s lymphoma. N Engl J Med. 2013;369(20):1915-1925. doi: 10.1056/nejmoa1308392.
  26. Hoelzer D, Walewski J, Döhner H, Viardot A, Hiddemann W, Spiekermann K, Serve H, Dührsen U, Hüttmann A, Thiel E, Dengler J, Kneba M, Schaich M, Schmidt-Wolf IG, Beck J, Hertenstein B, Reichle A, Domanska-Czyz K, Fietkau R, Horst H.A, Rieder H, Schwartz S, Burmeister T, Gökbuget N. Improved outcome of adult Burkitt lymphoma/leukemia with rituximab and chemotherapy: report of a large prospective multicenter trial. Blood. 2014;124(26):3870-3879. doi: 10.1182/blood-2014-03-563627.
  27. Hong J, Kim SJ, Ahn JS, Song MK, Kim YR, Lee HS, Yhim HY, Yoon DH, Kim MK, Oh SY, Park Y, Mun YC, Do YR, Ryoo HM, Lee JJ, Lee JH, Kim WS, Suh C. Treatment Outcomes of Rituximab Plus Hyper-CVAD in Korean Patients with Sporadic Burkitt or Burkitt-like Lymphoma: Results of a Multicenter Analysis. Cancer Res Treat. 2014 Oct 28. doi: 10.4143/crt.2014.055. [epub ahead of print].
  28. Kelly JL, Toothaker SR, Ciminello L, Hoelzer D, Holte H, LaCasce AS, Mead G, Thomas D, Van Imhoff GW, Kahl BS, Cheson BD, Magrath IT, Fisher RI, Friedberg JW. Outcomes of patients with Burkitt lymphoma older than age 40 treated with intensive chemotherapeutic regimens. Clin Lymphoma Myeloma. 2009;9(4):307-310. doi: 10.3816/clm.2009.n.060.

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