Combined chemoimmunotherapy of patients with mature B-cell non-Hodgkin lymphomas age group until 18 years: results of multicenter study NHL 2004 m with rituximab and modified B-NHL BFM 90 protocol applications
https://doi.org/10.17650/1818-8346-2009-0-3-4-14
Abstract
Therapy results of 61 patients (children and adolescents, 2—17 years of age; a median — 8.76 years) with B-cells non-Hodgkin lymphomas III—IV stage and B-cell acute leukemia (B-NHL/B-ALL), treating according to protocol with polichemotherapy and monoclonal antibodies against B-cell receptor CD20 — rituximab (Mabthera, Hoffmann La Roche) applications, are presented. The protocol consist of cytoreductive phase and 6 polychemotherapy courses, similar to original protocol B-NHL-BFM 90, with exception of decreasing methotrexate dosage in 2 first courses from 5 to 1 g/m2/24 hours. Rituximab — 375 mg/m2 IV — in Day 0 first 4 courses was given.
Four patients have died within first 3 weeks of therapy, 2 were primary refractory patients and 55 patients have achieved complete remissions. There was no case of remission death; relapse has developed only at one patient (neuroleukemia in patient with Burkitt lymphoma). 54 patients (88%) are in continuous complete remission. Overall and event-free survival rate were 0,90±0,04 with median follow-up after therapy ending 34 months (12—53 months). Authors discuss tactics of such combined therapy, features of remission registration, considering that at third of patients, residual mass was long-term detected, and for which assessment besides CT/MRT a positron-emission tomography (PET) and/or a repeated biopsy were done. Also it is possible to conclude that with use of target therapy chemotherapy intensity of such tumors can be reduced. Authors concluded that in cases of target therapy efficacy criteria should be modified, and it is necessary to use as much as possible informative technique to remission control (PET, minimal residual disease assessment with use of molecular-genetic methods).
About the Authors
E. V. SamochatovaRussian Federation
Moscow
L. N. Schelikhova
Russian Federation
Moscow
M. B. Belogurova
Russian Federation
St-Petersburg
A. V. Schamardina
Russian Federation
N. Novgorod
E. V. Bascharova
Russian Federation
Chelyabinsk
D. V. Litvinov
Russian Federation
Moscow
N. V. Myakova
Russian Federation
Moscow
L. G. Fechina
Russian Federation
Yekaterinburg
O. P. Chlebnikova
Russian Federation
Yekaterinburg
E. V. Inuschkina
Russian Federation
Balashicha
O. V. Riskal
Russian Federation
Perm
P. Z. Schammasov
Russian Federation
Kazan
I. M. Yunusova
Russian Federation
Makhachkala
S. Yu. Umnova
Russian Federation
Irkutsk
D. M. Konovalov
Russian Federation
Moscow
A. G. Talalaev
Russian Federation
Moscow
J. V. Roumiantseva
Russian Federation
Moscow
A. A. Maschan
Russian Federation
Moscow
References
1. Magrath I. B-Cell lymphoma/Burkitt lymphoma. In: Pediatric Lymphomas. Ed. H.J. Weinstein, M.M. Hudson, M.P. Link. Berlin, 2007. р. 142—68.
2. Magrath I. The non-Hodgkin’s lymphomas in children. In: Oxford Textbook of Oncology. Oxford: Oxford Medical Publications, 1995. p. 1809—51.
3. Murphy S.B., Bowman W.P., Abromowitch M. et al. Results of treatment of advanced-stage Burkitt’s lymphoma and B-cell (sIg+) acute lymphoblastic leukemia with high-dose fractionated cyclophosphamide and coordinated high-dose methotrexate and cytarabine. J Clin Oncol 1986;4:1732—9.
4. Pathology & Genetics. Tumours of Haematopoietic and Lymphoid Tissues. Ed. E.S. Jaffe, N.L. Harris, Y. Stein, J.W. Vardiman. Lion, 2001.
5. Reiter A., Schrappe M., Parwaresch R. et al. Non-Hodgkin’s lymphomas of childhood and adolescents: results of a treatment stratified for biologic subtypes and stage — a report of the BFM Group. J Clin Oncol 1995;13:359—72.
6. Patte C., Philip T., Rodary C. et al. High survival rate in advanced-stage B-cell lymphomas and leukemias without CNS involvement with a short intensive polychemotherapy: results from the French Pediatric Oncology Society of a randomized trial of 216 children. J Clin Oncol 1991;9:123—32.
7. Goldman S., Gerard M., Sposto R. et al. Excellent results in children and adolescents with isolated mature B-cell acute lymphoblastic leukemia (B-ALL) (Burkitt): Report from the FAB International LMB study FAB/LMB 96. Proc Am Hem 2005;106:72a.
8. Patte С. Treatment strategies and outcome in childhood B-cell lymphoma. Ped Blood Cancer 2006;46(7):834.
9. Burkhardt B. Outcome of adolescents with NHL: the BFM experience. Ped Blood Cancer 2006;46(7):847.
10. Shiramizu B., Goldman S., Lynch J. et al. Minimal residual disease (MRD) assessment in children and adolescents with mature B-cell non-Hodgkin lymphoma (B-NHL): a Children’s Oncology Group report. Hematol meet report 2009;3(5):14.
11. Reiter A., Schrappe M., Tiemann M. et al. Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy: a report of the Berlin-Frankfurt-Munster Group Trial NHL-BFM-90. Blood 1999;94(10):3294—306.
12. Cairo M.S., Sposto R., Gerrard M. et al. Risk factors associated with poor outcome in children and adolescents (c&a) with mature B-NHL: report of the FAB/LMB 96 Study. Hematol meet report 2009;3(5):20.
13. Semochkin S., Bobkova M., Kulikova S. et al. Modified NHL-BFM 90 protocol for adolescents and young adults with Burkitt lymnphoma (BL), mature B-cell ALL and diffuse large B-cell lymphoma (DLBCL). Hematol meet report 2009;3(5):53.
14. Morozova O., Slugin A., Mahonova L. et al. Treatment of childhood NHL with NHL-BFM 90/95 protocols. Hematol meet report 2009;3(5):94.
15. Minard-Colin V., Horikawa M., Xiu Y. Immune effector mechanisms of CD20 monoclonal antibodies. Hematol meet report 2009;3(5):19.
16. Pfreundshuh M., Trumper L., Glass B. et al. Randomized intergroup trial of first-line treatment for patients <60 years with diffuse large B-cell lymphoma (DLBCL) with a CHOP-like regimen with and without the anti-CD20 antibody rituximab — early stopping after first interim analysis. Blood 2002;11:65.
17. Coiffer B., Lepage E., Brier J. et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large B-cell lymphoma. N Engl J Med 2002;346:235.
18. Hoelzer D., Hiddemann W., Baumann A. et al. High cure rate of adult Burkitt’s and other high grade NHL by the combination of short intensive chemotherapy cycles with rituximab. Haematologica 2007;92(1):151.
19. Meinhardt A., Burkhardt B., Zimmermann M. et al. Results of a phase II window study on rituximab in newly diagnosed pediatreic mature B-cell NHL / Burkitt’s leukemia (B-ALL). Hematol meet report 2009;3(5):21.
20. De Vries M.J., Veerman A.J., Zwaan C.M. Rituximab in three children with relapsed/refractory B-cell acute lymphoblastic leukemia/Burkitt non-Hodgkin’s lymphoma. Br J Haematol 2004;25:414—5.
21. Самочатова Е.В., Шелихова Л.Н., Мякова Н.В. и др. Лечение неходжкинских лимфом и острого лимфобластного лейкоза из зрелых В-клеток (В-НХЛ/ОЛЛ) у детей и подростков с использованием интенсивной полихимиотерапии и ритуксимаба (протокол В-НХЛ 2004м): предварительные результаты. Гематол трансфузиол 2007;(6):9—17.
22. Samochatova E., Myakova N., Shelikhova L. et al. Preliminary results of treatment of pediatric advance-staged mature B-cell non-Hodgkin lymphomas/B-ALL with intensive hemotherapy + rituximab: effectiveness and toxicity. Ped Blood Cancer 2006;46(7):854.
23. Самочатова Е.В., Мякова Н.В., Литвинов Д.В. и др. Применение Ритуксимаба (Мабтера) в комбинированном лечении В-клеточных неходжкинских лимфом у детей: предварительные результаты. Вопр гематол онкол и иммунопатол педиатр 2004;3(4):54—60.
24. Самочатова Е.В., Шелихова Л.Н., Мякова Н.В. и др. Ритуксимаб (Мабтера) в лечении диффузных В-крупноклеточных лимфом у детей и подростков. Дет онкол 2007;(3—4):50—7.
25. Dunleavy K., Little R.F., Grant N. et al. Dose-adjusted EPOCH with rituximab (DA-EPOCH-R) has high efficacy and low toxicity in young adults with newly diagnosed Burkitt lymphoma — a prospective study of 25 patients. Hematol meet report 2009;3(5):52.
26. Goldman S., Lynch J., Harrison L. et al. Safety and kinetics of rituximab (R) following chemoimmunotherapy (R + FAB CT) in children and adolescents with mature B-cell non-Hodgkin lymphoma (B-NHL): a Children’s Oncology Group report. Hematol meet report 2009;3(5):81.
27. Gerrard M., Waxman I., Sposto R. et al. Primary mediastinal B-cell lymphoma (PMBL) in children (c) and adolescents (a) is associated with a significantly inferior prognosis: report of the FAB/LMB 96 Study Committee. Hematol meet report 2009;3(5):51.
28. Dunleavy K., Pittaluga S., Grant N. et al. The addition of rituximab to doseadjusted EPOCH (DA-EPOCH) obviates the need for radiation treatment in young adultes with primary mediastinal B-cell lymphoma. Hematol meet report 2009;3(5):50.
29. Menhardt A., Schadwill S., Zimmermann M. et al. Serum immunoglobulin levels in children and adolescents after B-NHL BFM chemotherapy with and without one dose of Rituximab. Hematol meet report 2009;3(5):23.
30. Sandlund J.T. Response evaluation: pediatric non-Hodgkin lymphoma. Hematol meet report 2009;3(5):11.
31. Cheson B., Pfister B., Juweid M. et al. Revised response criteria for malignant lymphoma. J Clin Oncol 2007;25(5):579—86.
32. Terui Y., Hatake K. Identification of CD20 mutations in malignant lymphonma: can they be predictors of response to rituximab? Clin Cancer Res 2009;15:2523.
33. Mussolin L., Pillon M., Tridello G. et al. Minimal disseminated disease identifies a poor prognosis subgroup among high risk Burkitt’s lymphoma patients. Hematol meet report 2009;3(5):12.
Review
For citations:
Samochatova E.V., Schelikhova L.N., Belogurova M.B., Schamardina A.V., Bascharova E.V., Litvinov D.V., Myakova N.V., Fechina L.G., Chlebnikova O.P., Inuschkina E.V., Riskal O.V., Schammasov P.Z., Yunusova I.M., Umnova S.Yu., Konovalov D.M., Talalaev A.G., Roumiantseva J.V., Maschan A.A. Combined chemoimmunotherapy of patients with mature B-cell non-Hodgkin lymphomas age group until 18 years: results of multicenter study NHL 2004 m with rituximab and modified B-NHL BFM 90 protocol applications. Oncohematology. 2009;(3):4-14. (In Russ.) https://doi.org/10.17650/1818-8346-2009-0-3-4-14