The Effect of Anticoagulant Therapy on Survival and Outcome of Venous Thrombosis in Children, Teenagers, and Young Adults with Acute Lymphoblastic Leukemia Treated According to ALL-MB-2008 and ALL-MB-2015 Protocols

VV Dmitriev, NV Migal, OI Bydanov, NV Lipai, EV Dmitriev

Republican National Applied Research Center of Pediatric Oncology, Hematology and Immunology, 43 Frunzenskaya, Borovlyany, Minskii district, Republic of Belarus, 223053

For correspondence: Vyacheslav Vasil’evich Dmitriev, MD, PhD, 43 Frunzenskaya str., Borovlyany, Minskii district, Republic of Belarus, 223053; Tel.: +375(17)265-42-22; e-mail:

For citation: Dmitriev VV, Migal NV, Bydanov OI, et al. The Effect of Anticoagulant Therapy on Survival and Outcome of Venous Thrombosis in Children, Teenagers, and Young Adults with Acute Lymphoblastic Leukemia Treated According to ALL-MB-2008 and ALL-MB-2015 Protocols. Clinical oncohematology. 2019;12(3):338–43 (In Russ).

doi: 10.21320/2500-2139-2019-12-3-338-343


Aim. To assess the effect of anticoagulant therapy on survival and outcome of venous thrombosis in children, teenagers, and young adults with acute lymphoblastic leukemia (ALL).

Materials & Methods. Venous thrombosis was diagnosed in 42 out of 592 ALL patients treated according to ALL-MB-2008 and ALL-MB-2015 protocols from 2008 to 2017.

Results. A daily dose of 150–200 IU/kg low molecular weight heparin (LMWH) was administered to 30 patients. Duration of anticoagulant treatment was up to 1 month in 4 patients, 2–3 months in 8 patients, 4–6 months in 12 patients, and 7–12 months in 4 patients. To 2 patients anticoagulants were administered for more than 24 months. Complete recanalization of thrombosed vessel was achieved in 19 patients, partial recanalization was achieved in 6 patients, obliteration of predominantly internal jugular vein was found in 5 patients. During thrombocytopenia (100 to 35 × 109/L) 12 patients received reduced doses of LMWH for 1–4 weeks. In the period of chemotherapy-induced thrombocytopenia the daily LMWH dose was reduced in proportion to thrombocyte level. After thrombocyte recovery up to more than 100 × 109/L antithrombotic treatment was continued with LMWH daily dose of 150–200 anti-Xa IU/kg. The duration of anticoagulant treatment among 12 patients who received reduced doses of LMWH was up to 1 month in 3 patients, 2–3 months in 4 patients, 4–6 months in 3 patients, and 7–12 months in 2 patients. Complete recanalization of thrombosed vessel was achieved in 8 patients, partial recanalization was achieved in 2 patients, vein obliteration was found in 2 patients. No correlation between LMWH dosage and thrombosis outcome was observed (χ2 = 0.494; = 0.78). Maintenance (accompanying) therapy was completed in 38 out of 42 ALL patients with venous thrombosis. Event-free survival was 83 ± 8 %, that was similar to the one (81 ± 2 %) in patients without thrombosis (= 0.654).

Conclusion. Anticoagulant treatment of venous thrombosis complicating ALL in children, teenagers, and young adults did not yield a decrease of either overall or event-free survival. Reduction of LMWH doses in the period of chemotherapy-induced thrombocytopenia did not affect the outcome of venous thrombosis.

Keywords: venous thrombosis, coagulation, acute lymphoblastic leukemia, children, teenagers, young adults, anticoagulant therapy, low molecular weight heparin.

Received: October 30, 2018

Accepted: June 5, 2019

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  1. Жарков П.А., Румянцев А.Г., Новичкова Г.А. Венозные тромбозы у детей со злокачественными новообразованиями (обзор литературы). Российский журнал детской гематологии и онкологии. 2015;2(1):66–74. doi: 10.17650/2311-1267-2015-1-66-74.

    [Zharkov PA, Rumyantsev AG, Novichkova GA. Venous thromboembolism in children with cancer. Russian Journal of Pediatric Hematology and Oncology. 2015;2(1):66–74. doi: 10.17650/2311-1267-2015-1-66-74. (In Russ)]

  2. Raetz EA, Salzer WL. Tolerability and efficacy of L-asparaginase therapy in pediatric patients with acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2010;32(7):554–63. doi: 10.1097/mph.0b013e3181e6f003.

  3. Payne JH, Vora AJ. Thrombosis and acute lymphoblastic leukemia. Br J Haematol. 2007;138(4):430–45. doi: 10.1111/j.1365-2141.2007.06677.x.

  4. Athale UH, Laverdiere C, Nayiager T, et al. Evaluation for inherited and acquired prothrombotic defects predisposing to symptomatic thromboembolism in children with acute lymphoblastic leukemia: a protocol for a prospective, observational, cohort study. BMC Cancer. 2017;17(1):313. doi: 10.1186/s12885-017-3306-5.

  5. Tuckuviene R, Ranta S, Albertsen BK, et al. Prospective study of thromboembolism in 1038 children with acute lymphoblastic leukemia: a Nordic Society of Pediatric Hematology and Oncology (NOPHO) study. J Thromb Haemost. 2016;14(3):485–94. doi: 10.1111/jth.13236.

  6. Caruso V, Iacoviello L, Di Castelnuovo A, et al. Thrombotic complications in childhood acute lymphoblastic leukemia: a meta-analysis of 17 prospective studies comprising 1752 pediatric patients. Blood, 2006;108(7):2216–22. doi: 10.1182/blood-2006-04-015511.

  7. Mitchell L, Lambers M, Flege S, et al. Validation of a predictive model for identifying an increased risk for thromboembolism in children with acute lymphoblastic leukemia: results of a multicenter cohort study. 2010;115(24):4999–5004. doi: 10.1182/blood-2010-01-263012.

  8. Appel IM, Hop WCJ, van Kessel-Bakvis C, et al. L-Asparaginase and the effect of age on coagulation and fibrinolysis in childhood acute lymphoblastic leukemia. Thromb Haemost. 2008;100(08):330–7. doi: 10.1160/th07-10-0620.

  9. Kearon С, Akl E, Ornelas J, et al. Antithrombotic Therapy for VTE Disease. CHEST Guideline and Expert Panel Report. CHEST. 2016;149 (2):315–52. doi: 10.1016/j.chest.2015.11.026.

  10. Carrier M, Khorana AA, Zwicker JI, et al. Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH. J Thromb Haemost. 2013;11(9):1760–5. doi: 10.1111/jth.12338.

  11. Saccullo G, Malato A, Raso S, et al. Cancer patients requiring interruption of long-term warfarin because of surgery or chemotherapy induced thrombocytopenia: the use of fixed subtherapeutic doses of low molecular weight heparin. Am J Hematol. 2012;87(4):388–91. doi: 10.1002/ajh.23122.

  12. Kerlin B, Stephens J, Hogan M, et al. Development of a Pediatric-Specific Clinical Probability Tool for Diagnosis of Venous Thromboembolism: A Feasibility Study. Pediatr Res. 2014;77(3):463–71. doi: 10.1038/pr.2014.198.

  13. Babilonia KM, Golightly LK, Gutman JA, et al. Antithrombotic Therapy in Patients With Thrombocytopenic Cancer: Outcomes Associated With Reduced-Dose, Low-Molecular-Weight Heparin During Hospitalization. Clin Appl Thromb Hemost. 2014;20(8):799–806. doi: 10.1177/1076029614543140.

  14. Dmitriev Nadroparin and dalteparin pharmacokinetics in thromboses complicated the treatment of children with oncological diseases. The Book of Abstracts The Congress on Open Issues in Thrombosis and Hemostasis 2018 jointly with the 9th Russian Conference on Clinical Hemostasiology and Hemorheology, Saint Petersburg, Russia October 4–6, 2018. pp 60.

Diagnosis of Pediatric-Type Follicular Lymphoma in Young Adults (Own Data)

AM Kovrigina, LV Plastinina, SK Kravchenko, ES Nesterova, TN Obukhova

Hematology Research Center under the Ministry of Health of the Russian Federation, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Alla Mikhailovna Kovrigina, DSci, Professor, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel: +7(495)612-62-12; e-mail:

For citation: Kovrigina AM, Plastinina LV, Kravchenko SK, et al. Diagnosis of Pediatric-Type Follicular Lymphoma in Young Adults (Own Data). Clinical oncohematology. 2017;10(1):52–60 (In Russ).

DOI: 10.21320/2500-2139-2017-10-1-52-60


Aim. Pathomorphological, immunophenotypical and clinical characteristics of a new clinico-morphological form of pediatric-type follicular lymphoma (FL) in young adults discovered in 2008 (WHO classification).

Background. FL is a heterogeneous disease according to its morphological, immunophenotypical and molecular-genetic characteristics. FL de novo includes transformed FL, FL without t(14;18), FL with diffuse growth associated with del(1p.36) and TNFRSF14 mutation. Pediatric-type FL in young adults is poorly studied; and it is especially interesting because of its clinical diversity and molecular-genetic heterogeneity of FL, in general.

Methods. Biopsy materials taken from 5 patients (aged 18–25 years; median age: 22 years; the female/male ratio 3:2) were included in the study; all patients were examined, diagnosed and treated in the Hematology Research Center over the period from 2012 to 2016. Clinical stage I with isolated involvement a palatine tonsil or an inguinal lymph node was diagnosed in 4/5 patients; clinical stage II with involvement of a palatine tonsil and cervical lymph node was diagnosed in 1/5 patients. Morphological, immunophenotypical and FISH tests were performed with paraffin blocks.

Results. The morphological pattern was typical for FL 3B (n = 2) and FL 3 with blastoid nucleus morphology (n = 3). Immunophenotypical features demonstrated an intermediate position between FL 3 de novo and transformed FL 3. No BCL-2 rearrangement was detected in any observation.

Conclusion. The comparison of our data on characteristics of pediatric-type FL with those published in the literature demonstrated that lack or weak expression (< 30 % of tumor substrate cells) of MUM1 was the key feature of the experimental group of young adults with pediatric-type FL. This, in turn, indicates the absence of IRF4 rearrangements and possible presence of other genetic abnormalities. The clinical, morphological, and immunophenotypical characteristics broaden the FL heterogeneity spectrum in young adults.

Keywords: pediatric-type follicular lymphoma, follicular lymphoma, young adults, pathomorphology, immunohictochemistry, MUM1.

Received: August 14, 2016

Accepted: November 27, 2016

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  1. Lennert K, Stein H, Mohri N, et al. Malignant Lymphomas Other than Hodgkin’s Disease: Histology, Cytology, Ultrastructure, Immunology. Berlin, Heidelberg: Springer-Verlag; 1978. 833 p. doi: 10.1016/0092-8674(79)90172-7.
  2. Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th edition. Lyon: IARC Press; 2008.
  3. Anderson JR, Armitage JO, Weisenburger DD. Epidemiology of the non-Hodgkin’s lymphomas: distributions of the major subtypes differ by geographic locations. Non-Hodgkin’s Lymphoma Classification. Project Ann Oncol. 1998;9(7):717–20.
  4. Gallagher CJ, Gregory WM, Jones AE, et al. Follicular lymphoma: Prognostic factors for response and survival. J Clin Oncol. 1986;4(10):1470–80.
  5. Bastion Y, Sebban C, Berger F, et al. Incidence, predictive factors, and outcome of lymphoma transformation in follicular lymphoma patients. J Clin Oncol. 1997;15(4):1587–94.
  6. Montoto S, Davies AJ, Matthews J, et al. Risk and clinical implications of transformation of follicular lymphoma to diffuse large B-cell lymphoma. J Clin Oncol. 2007;25(17):2426–33. doi: 10.1200/jco.2006.09.3260.
  7. Montoto, S., Fitzgibbon J. Transformation of indolent B-cell lymphomas. J Clin Oncol. 2011;29(4):1827–34. doi: 10.1200/JCO.2010.32.7577.
  8. Hirt C, Weitmann K, Schuler F, et al. Circulating t(14;18)-positive cells in healthy individuals: association with age and sex but not with smoking. Leuk Lymphoma. 2013;54(12):2678–84. doi: 10.3109/10428194.2013.788177.
  9. Weigert O, Kopp N, Lane AA, et al. Molecular ontogeny of donor derived follicular lymphomas occurring after hematopoietic cell transplantation. Cancer Discov. 2012;2(1):47–55. doi: 10.1158/
  10. Leich E, Salaverria I, Bea S, et al. Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations. Blood. 2009;114(4):826–34. doi: 10.1182/blood-2009-01-198580.
  11. Kridel R, Sehn LH, Gascoyne RD. Pathogenesis of follicular lymphoma. J Clin Invest. 2012;122(10):3424–31. doi: 10.1172/jci63186.
  12. Katzenberger T, Kalla J, Leich E, et al. A distinctive subtype of t(14;18)-negative nodal follicular non- Hodgkin lymphoma characterized by a predominantly diffuse growth pattern and deletions in the chromosomal region 1p36. Blood. 2009;113(5):1053–61. doi: 10.1182/blood-2008-07-168682.
  13. Pasqualucci L, Khiabanian H, Fangazio M, et al. Genetics of Follicular Lymphoma Transformation. Cell Reports. 2014;6(1):130–40. doi: 10.1016/j.celrep.2013.12.027.
  14. Bouska A, McKeithan TW, Deffenbacher KE, et al. Genome-wide copy-number analyses reveal genomic abnormalities involved in transformation of follicular lymphoma. Blood. 2014;123(11):1681–90. doi: 10.1182/blood-2013-05-500595.
  15. Lorsbach RB, Shay-Seymore D, Moore J, et al. Clinicopathologic analysis of follicular lymphoma occurring in children. Blood. 2002;99(6):1959–64. doi: 10.1182/blood.v99.6.1959.
  16. Swerdlow SH. Pediatric follicular lymphomas, marginal zone lymphomas, and marginal zone hyperplasia. Am J Clin Pathol. 2004;122(Suppl 1):S98–S109. doi: 10.1309/4bknake4d7ct3c1b.
  17. Oschlies I, Salaverria I, Mahn F, et al. Pediatric follicular lymphoma—a clinico-pathological study of a population-based series of patients treated within the Non-Hodgkin’s Lymphoma—Berlin-Frankfurt-Munster (NHL-BFM) multicenter trials. Haematologica. 2010;95(2):253–9. doi: 10.3324/haematol.2009.013177.
  18. Liu Q, Salaverria I, Pittaluga S, et al. Follicular lymphomas in children and young adults: a comparison of the pediatric variant with usual follicular lymphoma. Am J Surg Pathol. 2013;37(3):333–43. doi: 10.1097/pas.0b013e31826b9b57.
  19. Louissaint A, Ackerman A, Dias-Santagata D, et al. Pediatric-type nodal follicular lymphoma: an indolent clonal proliferation in children and adults with high proliferation index and no BCL2 rearrangement. Blood. 2012;120(12):2395–404. doi: 10.1182/blood-2012-05-429514.
  20. Guo Y, Karube K, Kawano R, et al. Low-grade follicular lymphoma with t(14;18) presents a homogeneous disease entity otherwise the rest comprises minor groups of heterogeneous disease entities with Bcl2 amplification, Bcl6 translocation or other gene aberrances. Leukemia. 2005;19(6):1058–63. doi: 10.1038/sj.leu.2403738.
  21. Katzenberger T, Ott G, Klein T, et al. Cytogenetic alterations affecting BCL6 are predominantly found in follicular lymphomas grade 3B with a diffuse large B-cell component. Am J Pathol. 2004;165(2):481–90. doi: 10.1016/s0002-9440(10)63313-5.
  22. Salaverria I, Siebert R. Follicular lymphoma grade 3B. Best Pract Res Clin Haematol. 2011;24(2):111–9. doi: 10.1016/j.beha.2011.02.002.
  23. Ngan BY, Chen-Levy Z, Weiss LM, et al. Expression in non- Hodgkin lymphoma of the bcl-2 protein associated with the t(14;18) chromosomal translocation. N Engl J Med. 1988;318(25):1638–44. doi: 10.1056/nejm198806233182502.
  24. Adam P, Baumann R, Schmidt J, et al. The BCL2 E17 and SP66 antibodies discriminate 2 immunophenotypically and genetically distinct subgroups of conventionally BCL2-“negative” grade 1/2 follicular lymphomas. Hum Pathol. 2014;44(9):1817–26. doi: 10.1016/j.humpath.2013.02.004.
  25. Lorsbach RB, Shay-Seymore D, Moore J, et al. Clinicopathologic analysis of follicular lymphoma occurring in children. Blood. 2002;99(6):1959–64. doi: 10.1182/blood.v99.6.1959.
  26. Willis SN, Good-Jacobson KL, Curtis J, et al. Transcription Factor IRF4 Regulates Germinal Center Cell Formation through a B Cell–Intrinsic Mechanism. J Immunol. 2014;192(7):3200–6. doi: 10.4049/jimmunol.1303216.
  27. Karube K, Guo Y, Suzumiya J, et al. CD10- MUM1+ follicular lymphoma lacks BCL2 gene translocation and shows characteristic biologic and clinical features. Blood. 2007;109(7):3076–9. doi: 10.1182/blood-2006-09-045989.
  28. Sweetenham JW, Goldman B, LeBlanc ML, et al. Prognostic value of regulatory T cells, lymphoma-associated macrophages, and MUM-1 expression in follicular lymphoma treated before and after the introduction of monoclonal antibody therapy: a Southwest Oncology Group Study. Ann Oncol. 2010;21(6):1196–202. doi: 10.1093/annonc/mdp460.
  29. Xerri L, Bachy E, Fabiani B, et al; LYSA study. Identification of MUM1 as a prognostic immunohistochemical marker in follicular lymphoma using computerized image analysis. Hum Pathol. 2014;45(10):2085–93. doi: 10.1016/j.humpath.2014.06.019.
  30. Salaverria I, Philipp C, Oschlies I, et al. Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults. Blood. 2011;118(1):139–47. doi: 10.1182/blood-2011-01-330795.
  31. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–90. doi: 10.1182/blood-2016-01-643569.
  32. Quintanilla-Martinez L, Sander B, Chan JK, et al. Indolent lymphomas in the pediatric population: follicular lymphoma, IRF4/MUM1+ lymphoma, nodal marginal zone lymphoma and chronic lymphocytic leukemia. Virchows Arch. 2016;468(2):141–57. doi: 10.1007/s00428-015-1855-z.
  33. Jaffe ES. Follicular lymphomas: a tapestry of common and contrasting threads. Haematologica. 2013;98(8):1163–5. doi: 10.3324/haematol.2013.086678.
  34. Martin-Guerrero I, Salaverria I, Burkhardt B, et al. Recurrent loss of heterozygosity in 1p36 associated with TNFRSF14 mutations in IRF4 translocation negative pediatric follicular lymphomas. Haematologica 2013;98(8):1237–41. doi: 10.3324/haematol.2012.073916.
  35. Launay E, Pangault C, Bertrand P, et al. High rate of TNFRSF14 gene alterations related to 1p36 region in de novo follicular lymphoma and impact on prognosis. Leukemia. 2012;26(3):559–62. doi: 10.1038/leu.2011.266.

Quality of life in adolescent and young adult Hodgkin’s lymphoma survivors

Ye.G. Arshanskaya1,2, S.V. Semochkin2,3, and A.G. Rumyantsev2,3

1 S.P. Botkin City Clinical Hospital, Moscow, Russian Federation

2 Federal Clinical-and-Research Center of Pediatric Hematology, Oncology, and Immunology n.a. Dmitriy Rogachev, Moscow, Russian Federation

3 N.I. Pirogov Russian National Research Medical University, RF Ministry of Health, Moscow, Russian Federation


Background. Deterioration of quality of life (QoL) and late complications of antitumor therapy for Hodgkin’s lymphoma (HL) are the important medical issues, since they mostly relate to young patients with a high life-expectancy.

Objective. The study was to compare QoL of HL survivors versus healthy young adults.

Methods. 56 (22 males and 34 females) HL survivors with a median age of 27.5 (range 22–41) were evaluated. For the purpose of comparison, 94 (44 males and 50 females) healthy subjects with a median age of 28.0 (range 22–46) were enrolled into the study of QoL. All HL survivors were treated in our hospital according to the modified pediatric protocol DAL-HD-90 in 1997–2007. QoL was assessed using the Short Form 36 (SF-36) which enabled generating 8 separate scales and 2 final scores (0 = worst possible health, 100 = best possible health). All survivors were in complete remission of HL for ³ 5 years.

Results. The HL survivors had the lower scores than the normal controls according to all scales and SF-36. Statistically significant differences were found in: general health — 53.4 (95 %CI 47.8–59.1) vs. 72.3 (68.8–75.8; < 0,001), vitality — 54.7 (50.4–59.1) vs. 72.2 (69.3–75.2; < 0.001), and mental health — 57.4 (53.5–61.4) vs. 71.7 (68.6–74.8; < 0.001). The patients at the age ³ 18.5 years (ROC-curves; = 0.047) at the time of HL diagnosis had poorer QoL when compared to younger patients with respect to: general health — 48.3 (41.3–55.2) vs. 60.9 (51.6–70.2; = 0.027): vitality — 50.3 (44.7–55.9) vs. 61.1 (51.6–70.2; = 0.013). The patients with the unfavorable events including relapse (n = 6) and second malignancy (n = 2) showed the lowest scores of QoL, especially in physical role performance [34.4 (2.6–71.3) vs. 79.7 (77.8–89.6; = 0.002)] and emotional role performance [25.0 (7.5–57.5) vs. 77.8 (67.1–88.4; < 0.001)]. Duration of remission, age at the QoL evaluation, gender, therapy intensity (2, 4, or 6 cycles of primary chemotherapy plus radiotherapy), Ann-Arbor stages, bulky disease, current married status, and education levels showed no significant influence on the QoL parameters.

Conclusion. Long-term HL survivors had poorer physical and mental QoL than the general population of young adults. The age at the time of LH diagnosis ³ 18.5 years was associated with significantly reduced QoL. The relapsed HL and second malignancies were mostly associated with the deterioration of physical and emotional role functioning that may indicate uncertainty of patients about future well-being.

Keywords: Hodgkin’s lymphoma, quality of life, adolescents, young adults, DAL-HD-90, SF-36

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  1. Злокачественные новообразования в России в 2012 г. (заболева- емость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Пе- тровой. М.: ФГБУ «МНИОИ им. П.А. Герцена» МЗ РФ, 2014. [Sostoyaniye onkologicheskoy pomoshchi naseleniyu Rossii v 2012 g. Pod red. A.D. Kaprina, V.V. Starinskogo, G.V. Petrovoy (Status of oncological care for population of Russia in 2012. Ed. by A.D.Kaprin, V.V. Starinsky, and G.V. Petrova). M.: FGBU MNIO im. P.A. Gertsena Minzdravsotsrazvitiya Rossii 2014.]
  2. Morton L.M., Wang S.S., Devesa S.S. et al. Lymphoma incidence patterns by WHO subtype in the United States, 1992–2001. Blood 2006; 107(1): 265–76.
  3. Румянцев А.Г., Птушкин В.В., Семочкин С.В. Пути улучшения ре- зультатов лечения злокачественных опухолей у подростков и молодых взрослых. Онкогематология 2011; 1: 20–30. [Rumyantsev A.G., Ptushkin V.V., Semochkin S.V. Approaches to improvement of treatment outcomes in adolescents and young adults with malignancies. Onkogematologiya 2011; 1: 20–30. (In Russ.)].
  4. Evens A.M., Hutchings M., Diehl V. Treatment of Hodgkin lymphoma: the past, present, and future. Nat. Clin. Pract. Oncol. 2008; 5(9): 543–56.
  5. Sasse S., Klimm B., Gorgen H. et al. Comparing long-term toxicity and efficacy of combined modality treatment including extended- or involved-field radiotherapy in early-stage Hodgkin’s lymphoma. Ann. Oncol. 2012; 23(11): 2953–9.
  6. Robison L.L., Green D.M., Hudson M. et al. Long-term outcomes of adult survivors of childhood cancer. Cancer 2005; 104(11): 2557–64.
  7. Shah A.B., Hudson M.M., Poquette C.A. et al. Long-term follow-up of patients treated with primary radiotherapy for supradiaphragmatic Hodgkin’s disease at St. Jude Children’s Research Hospital. Int. J. Radiat. Oncol. Biol. Phys. 1999; 44(4): 867–77.
  8. Феоктистов Р.И., Румянцева Ю.В., Абугова Ю.Г. и др. Результаты лечения детей и подростков с лимфомой Ходжкина: данные многоцентро- вого исследования. Онкогематология 2010; 1: 31–6. [Feoktistov R.I., Rumyantseva Yu.V., Abugova Yu.G., et al. Treatment outcomes in children and adolescents with Hodgkin’s lymphoma: data of multicenter study. Onkogematologiya 2010; 1: 31–6. (In Russ.)].
  9. Schellong G., Riepenhausen M., Bruch C. et al. Late valvular and other cardiac diseases after different doses of mediastinal radiotherapy for Hodgkin disease in children and adolescents: report from the longitudinal GPOH followup project of the German-Austrian DAL-HD studies. Pediatr. Blood Cancer 2010; 55(6): 1145–52.
  10. Демина Е.А., Пылова И.В., Шмаков Р.Г., Перилова Е.Е. Поздние ослож- нения терапии больных лимфомой Ходжкина. Совр. онкол. 2006; 1: 36–43. [Demina Ye.A., Pylova I.V., Shmakov R.G., Perilova Ye.Ye. Late complications of therapy in patients with Hodgkin’s lymphoma. Sovr. onkol. 2006; 1: 36–43. (In Russ.)]. 11. Ng A.K., LaCasce A., Travis L.B. Long-term complications of lymphoma and its treatment. J. Clin. Oncol. 2011; 29(14): 1885–92.
  11. Gil-Fernandez J., Ramos C., Tamayo T. et al. Quality of life and psychological well-being in Spanish long-term survivors of Hodgkin’s disease: results of a controlled pilot study. Ann. Hematol. 2003; 82(1): 14–8.
  12. Khimani N., Chen Y.H., Mauch P.M. et al. Influence of new late effects on quality of life over time in Hodgkin lymphoma Survivors: a longitudinal survey study. Ann. Oncol. 2013; 24(1): 226–30.
  13. Hjermstad M.J., Fossa S.D., Oldervoll L. et al. Fatigue in long-term Hodgkin’s disease survivors: a follow-up study. J. Clin. Oncol. 2005; 23(27): 6587–95.
  14. Ruffer J.U., Flechtner H., Tralls P. et al. Fatigue in long-term survivors of Hodgkin’s lymphoma; a report from the German Hodgkin Lymphoma Study Group (GHSG). Eur. J. Cancer 2003; 39(15): 2179–86.
  15. Новик А.А., Ионова Т.И. Руководство по исследованию качества жизни в медицине. Под ред. Ю.Л. Шевченко, 2-е изд. М.: Олма Медиагрупп, 2007. [Novik A.A., Ionova T.I. Rukovodstvo po issledovaniyu kachestva zhizni v meditsine. Pod red. Yu.L. Shevchenko, 2-e izd. (Manual on evaluation of quality of life in medicine. Ed by.: Yu.L. Shevchenko, 2nd ed.) M.: Olma Mediagrup, 2007]
  16. Давыдкин И.Л., Булгакова С.В., Шафиева И.А. Подходы к реаби- литации пациентов в Самарском областном межведомственном центре профилактики остеопороза. Аллергол. и иммунол. 2007; 8(1): 276. [Davydkin I.L., Bulgakova S.V., Shafiyeva I.A. Approaches to rehabilitation of patients in Samara regional interdisciplinary center for osteoporosis prevention. Allergol. i immunol. 2007; 8(1): 276. (In Russ.)].
  17. Semochkin S.V., Arshanskaya E.G., Bobkova M.M., Rumiantsev A.G. A long-term follow-up report on the modified pediatric protocol DAL-HD-90 for adolescents and young adults with Hodgkin lymphoma. Pediatr. Blood Cancer 2012; 59(6): 1042.
  18. 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. [Semochkin S.V., Loriya S.S., Rumyantsev A.G., Sotnikov V.M. Management of Hodgkin’s lymphoma in adolescents and young adults. Onkogematologiya 2008; 1: 18–26. (In Russ.)].
  19. Ware J.E., Kosinski M. Interpreting SF-36 summary health measures: a response. Qual. Life Res. 2001; 10(5): 405–13.
  20. Van Tulder M.W., Aaronson N.K., Bruning P.F. The quality of life of longterm survivors of Hodgkin’s disease. Ann. Oncol. 1994; 5(2): 153–8.
  21. Loge J.H., Abrahamsen A.F., Ekeberg O., Kaasa S. Reduced healthrelated quality of life among Hodgkin’s disease survivors: a comparative study with general population norms. Ann. Oncol. 1999; 10(1): 71–7.
  22. Mols F., Vingerhoets A.J., Coebergh J.W. et al. Better quality of life among 10–15 year survivors of Hodgkin’s lymphoma compared to 5–9 year survivors: a population-based study. Eur. J. Cancer 2006; 42(16): 2794–801.

Optimization of diagnosis and treatment of Burkitt’s lymphoma in children, adolescents, and young adults

T.T. Valiyev1, Ye.A. Baryakh2, P.A. Zeynalova3, A.M. Kovrigina2, S.K. Kravchenko2, T.N. Obukhova2, N.А. Falaleyeva3, A.I. Senderovich3, I.N. Serebryakova3, I.V. Kaminskaya1, A.S. Levashov1, and G.L. Mentkevich1

1 Pediatric Oncology and Hematology Research Institute, N.N. Blokhin Russian Cancer Center, Moscow, Russian Federation

2 Hematology Research Center, RF Ministry of Health, Moscow, Russian Federation

3 Clinical Oncology Research Institute, N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation


We present the combined experience of the leading centers in diagnosis and treatment of Burkitt’s lymphoma (BL) in children, adolescents, and young adults, that is the first one in the national scientific literature. It includes immunolomorphologic and cytogenetic criteria of BL. The clinical features of BL in various age groups and treatment outcomes according to B-NHL-BFM 90/95 and CODOX-M/IVAC programs are described. Also, the treatment outcomes according to the original national LB-M-04 protocol are shown. The place of rituximab in BL treatment is discussed.

Keywords: Burkitt’s lymphoma, children, adolescents, young adults, clinical features, diagnosis, treatment.

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  1. Kasili E.G. Paediatric malignancy in tropical Africa — a growing concern. East. Afr. Med. J. 1986; 63: 685–6.
  2. Thomas D., Cortes J., O’Brien S. et al. Hyper-CVAD program in Burkitt’s type adult acute lymphoblastic leukemia. J. Clin. Oncol. 1999; 17(8): 2461–70.
  3. Ferry J.A. Burkitt’s Lymphoma: Clinicopathologic Features and Differential Diagnosis. Oncologist 2006; 11: 375–83.
  4. Swerdlow S.H., Campo E., Lee H.N. et al. WHO Classification of Tumours of Haematopoetic and Lymphoid tissues, 4th edn. Lyon: IARC Press, 2008: 439.
  5. Agugua N.E., Okeahialam T. Malignant diseases of childhood seen at the University of Nigeria Teaching Hospital, Enugu, Nigeria. East. Afr. Med. J. 1986; 63: 717–23.
  6. Oguonu T., Emodi E., Kaine W. Epidemiologie of Burkitt’s lymphoma in Enugu, Nigeria. Ann. Trop. Paediatr. 2002; 22: 369–74.
  7. Amusa Y.B., Adediran I.A., Akinpelu V.O. et al. Burkitt’s lymphoma of the head and neck region in a Nigeria tertiary hospital. East. Afr. J. Med. 2005; 24(3): 139–42.
  8. Kittivorapart J., Chinthammitr Y. Incidence and risk factors of bone marrow involvement by non-Hodgkin lymphoma. J. Med. Assoc. Thai. 2011; 94(Suppl. 1): S239–45.
  9. Барях Е.А., Кравченко С.К., Обухова Т.Н. и др. Лимфома Беркитта: клиника, диагностика, лечение. Клин. онкогематол. 2009; 2(2): 137–46. [Baryakh Ye.A., Kravchenko S.K., Obukhova T.N., et al. Burkitt’s lymphoma: clinical presentation, diagnosis, management. Klin. onkogematol. 2009; 2(2): 137–47. (In Russ.)].
  10. Blum K.A., Lozansky G., Byrd J. Adult Burkitt’s leukemia and lymphoma. Blood 2004; 20: 32–7.
  11. Braziel R.M., Arber D.A., Slovac M.L. et al. The Burkitt-like lymphoma: a Southwest Oncologie Group study delineating phenotypic, genotypic and clinical features. Blood 2001; 97(12): 3713–20.
  12. Martinez-Maza O., Breen E.C. B-cell activation and lymphoma in patients with HIV. Curr. Opin. Oncol. 2002; 14: 528–32.
  13. Magrath I.T. Malignant Non-Hodgkin’s Lymphomas in Children. Pediatr. Oncol. 2002; 119: 661–705.
  14. Zeigler J. Burkitt’s lymphoma. N. Engl. J. Med. 1981; 305: 735–45.
  15. Kelly G., Bell A., Rickinson A. Epstein-Barr virus-associated Burkitt lymphoma genesis selects for down-regulation of the nuclear antigen EBNA2. Nat. Med. 2002; 8(10): 1098–104.
  16. Гурцевич В.Э. Роль вируса Эпштейна—Барр в онкогематологиче- ских заболеваниях человека. Клин. онкогематол. 2010; 3(3): 222–35. [Gurtsevich V.E. Role of Epstein—Barr virus in human hematological malignancies. Klin. onkogematol. 2010; 3(3): 222–35. (In Russ.)].
  17. Magrath I. Epidemiology: clues to the pathogenesis of Burkitt lymphoma. Br. J. Haematol. 2012; 156(6): 744–56.
  18. Croce C. Role of chromosome translocations in human neoplasia. Cell 1987; 49(2): 155–6.
  19. Zech L., Haglund U., Nilsson K., Klein G. Characteristic chromosomal abnormalities in biopsies and lymphoid-cell lines from patients with Butkitt and non-Burkitt lymphomas. Int. J. Cancer 1976; 17: 47–56.
  20. Обухова Т.Н., Барях Е.А., Капланская И.Б. и др. Выявление диагности- ческих для лимфомы Беркитта транслокаций методом флюоресцентной in situ гибридизации на гистологических срезах парафиновых блоков. Тер. арх. 2007; 79(7): 80–3. [Obukhova T.N., Baryakh Ye.A., Kaplanskaya I.B., et al. Detection of translocations typical for Burkitt’s lymphoma using fluorescent hydrydization in situ in histological slices from paraffin blocks. Ter. arkh. 2007; 79(7): 80–3. (In Russ.)]
  21. Green T.M., Nielsen O., de Stricker K. et al. 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.
  22. Ben-Neriah S., Woods R., Steidl C. et al. Lymphomas with concurrent BCL2 and MYC translocations: the critical factors associated with survival. Blood 2009; 114: 2273–9.
  23. Tagawa H., Ikeda S., Sawada K. Role of microRNA in the pathogenesis of malignant lymphoma. Cancer Sci. 2013; 10; 121–6.
  24. Mead G.M., Sydes M.R., Walewski J. et al. 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): 1264–74.
  25. Costa L.J., Xavier A.C., Wahlquist A.E. еt al. Trends in survival of patients with Burkitt lymphoma/leukemia in the USA: an analysis of 3691 cases. Blood 2013; 121(24): 4861–6.
  26. 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. Lymph. Myel. 2007; 8(2): 57–62.
  27. Rizzieri D.A., Johnson J.L., Byrd J.C. et al. Efficacy and toxicity of rituximab and brief duration, high intensity chemotherapy with filgrastim support for Burkitt or Burkitt-like leukemia/lymphoma: Cancer and Leukemia Group B (CALGB) Study 10002 (abstract). Blood 2010; 116: Abstract 858.
  28. Dunleavy K., Pittaluga S., Wayne A.S. et al. MYC+ aggressive B-cell lymphomas: A novel therapy of untreated Burkitt lymphoma (BL) and MYC+ diffuse large B-cell lymphoma (DLBCL) with DA-EPOCH-R (abstract). Ann. Oncol. 2011; 22(4): Abstract 71.
  29. Griffin T.C., Weitzman S., Weinstein H. et al. A study of rituximab and ifosfamide, carboplatin, and etoposide chemotherapy in children with recurrent/ refractory B-cell (CD20+) non-Hodgkin lymphoma and mature B-cell acute lymphoblastic leukemia: A report from the Childrens Oncology Group. Pediatr. Blood Cancer 2009; 52: 177–81.
  30. Российские клинические рекомендации по диагностике и лечению лимфопролиферативных заболеваний. Под ред. И.В. Поддубной, В.Г. Савченко. М.: Медиа Медика, 2013: 102. [Rossiyskie klinicheskie rekomendatsii po diagnostike i lecheniyu limfoproliferativnykh zabolevaniy. Pod red. I.V. Poddubnoy, V.G. Savchenko (Russian clinical guidelines for diagnosis and treatment of lymphoproliferative disorders. Ed. by: I.V. Poddubnaya, V.G. Savchenko) M.: Media Medika, 2013: 102.]
  31. Барях Е.А., Валиев Т.Т., Яцков К.В. и др. Интенсивная терапия лимфомы Беркитта: описание двух клинических случаев. Гематол. и транс- фузиол. 2007; 52(1): 41–3. [Baryakh Ye.A., Valiyev T.T., Yatskov K.V., et al. Intensive therapy for Burkitt’s lymphoma: presentation of two clinical cases. Gematol. i transfuziol. 2007; 1: 41–3. (In Russ.)].
  32. Барях Е.А., Звонков Е.Е., Кременецкая А.М. Лечение беркиттопо- добной лимфомы взрослых. Тер. арх. 2006; 7: 53. [Baryakh Ye.A., Zvonkov Ye.Ye., Kremenetskaya A.M. Management of adult Burkitt-like lymphoma. Ter. arkh. 2006; 7: 53. (In Russ.)].
  33. Rosenfeld A., Arrington D., Miller J. et al. A review of childhood and adolescent craniopharyngiomas with particular attention to hypothalamic obesity. Pediatr. Neurol. 2014; 50(1): 4–10. doi: 10.1016/j.pediatrneurol.2013.09.003. Epub 2013 Nov 1.
  34. Senerchia A.A., Ribeiro K.B., Rodriguez-Galindo C. Trends in incidence of primary cutaneous malignancies in children, adolescents, and young adults: A population-based study. Pediatr. Blood Cancer 2014; 61(2): 211–6. doi: 10.1002/pbc.24639. Epub 2013 Oct 30.
  35. Тур А.Ф., Тарасов О.Ф., Шабалов Н.П. и др. Детские болезни, 2-е изд. М.: Медицина, 1985. [Tur A.F., Tarasov O.F., Shabalov N.P., et al. Detskiye bolezni, 2-e izd. (Pediatric disorders. 2nd ed.) M.: Meditsina, 1985]
  36. Bleyer A., Viny A., Barr R. Cancer in 15- to 29-year-olds by primary site. Oncologist 2006; 11(6): 590–601.
  37. Bleyer A. Young adult oncology: the patients and their survival challenges. СА Cancer J. Clin. 2007; 57(4): 242–55.
  38. Wood W.A., Lee S.J. Malignant hematologic diseases in adolescents and young adults. Blood 2011; 117: 5803–15.
  39. Sandlund J.T. Should adolescents with NHL be treated as old children or young adults? Hematol. Am. Soc. Hematol. Educ. Progr. 2007; 2007(1): 297–303.
  40. Cairo M.S., Sposto R., Gerrard M. et al. Advanced stage, increased, lactate dehydrogenase, and primary site, but not adolescent age (³ 15 years)are associated with an increased risk of treatment failure in children and adolescents with mature B-cell non-Hodgkins lymphoma: results of FAB LMB 96 Study. J. Clin. Oncol. 2012; 30(4): 387–93.
  41. Coiffier B. State-of-the-art therapeutics: diffuse large B-cell lymphoma. J. Clin. Oncol. 2005; 23(26): 6387–93.
  42. Pfreundschuh M., Trumper L., Osterborg A. et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good prognosis diffuse large B-cell lymphoma: a randomized controlled trial by the MabThera International Trial (MinT). Lancet Oncol. 2006; 7(5): 379–91.