Follicular lymphoma. High-dose immunochemotherapy with autologous blood stem cell transplantation: Results of the first prospective study in Russia

Abstract

Aim: To evaluate the efficiency of high-dose chemotherapy (HDCT) with further autologous blood stem cell transplantation (auto-BSCT) in the first-line therapy of patients with follicular lymphoma (FL) and poor prognostic factors. Subjects and methods. In 2000 to 2015, the National Research Center for Hematology, Ministry of Health of the Russian Federation, performed therapy in 39 patients with FL and poor prognostic factors (a total of 215 patients with FL). The R-CHOP treatment was done as induction therapy. Sequential HCT and further auto-BSCT were performed in 29 (74%) of the 39 patients, who had shown a partial tumor response to the induction therapy or achieved partial remission after 4-6 cycles of CT, but had poor prognostic factors. 22 of the 29 patients underwent auto-BSCT in first-line therapy after induction R-CHOP regimens. Among them, there were 17 men with a median age of 46 years (31-68 years). 21 of the 22 patients were recorded to have Stage IV by the Ann Arbor staging classification. Bulky peritoneal and retroperitoneal tumors larger than 7 cm were detectable at disease onset in 14 of the 22 cases. Two patients were noted to have phenomena of leukemization. 16 patients had bone marrow (BM) involvement. According to the Follicular Lymphoma International Prognostic Index-1 (FLIPI-1), the patients were divided into 3 groups: 1) a low risk (n=5); 2) an intermediate risk (n=3); a high risk (n=14). B-symptoms were observed in 16 cases. 16 patients were diagnosed with cytological grade I-II FL and 6 had grade IIIA. According to the tumor proliferative pattern, the distribution turned out to be as follows: nodular (n=6), nodular-diffuse (n=13), and diffuse (n=3). The proliferative activity index averaged 30% (8-90%). Serum and urine proteins were immmunochemically assayed in 18 cases, out of them 8 patients were diagnosed as having serum β2-microglobulin concentrations above normal as a poor prognostic factor. In 14 of the 22 patients, the activity of lactate dehydrogenase was greater than normal (266-7806 U/l). Results. Out of the 22 patients, 20 who have undergone auto-BSCT in first-line therapy are survivors and have remission of the underlying disease: 18 and 2 patients achieved complete and partial remission, respectively. The follow-up period was 7 to 178 months (median, 32 months). After auto-BSCT in the first remission, 2 patients developed disease recurrences: an early recurrence after 9 months in one case and a late recurrence 6 years after completion of therapy in the other. Conclusion. The first prospective study of intensive therapy for FL in Russia has demonstrated that HDCT with further auto-BSCT in first-line therapy allows complete remission in patients with poor prognostic factors and higher overall and progression-free survival rates.

References

  1. Давыдов М.И., Аксель Е.М. Статистика злокачественных новообразований в России и странах СНГ в 2009. Вестник РОНЦ им. Н.Н. Блохина РАМН. 2011;22(1).
  2. Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Dürk H,Ballo H, Stauch M, Roller F, Barth J, Hoelzer D, Hinke A, Brugger W; Study group indolent Lymphomas (StiL). Bendamustine plus rituximab versus CHOP plus rituximab as fi rst-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013;381(9873): 1203-1210.
  3. Ladetto M, De Marco F, Benedetti F, Vitolo U, Patti C, Rambaldi A, Pulsoni A, Musso M, Liberati AM, Olivieri A, Gallamini A, Pogliani E, Rota Scalabrini D,Callea V, Di Raimondo F, Pavone V, Tucci A, Cortelazzo S, Levis A, Boccadoro M, Majolino I, Pileri A, Gianni AM, Passera R, Corradini P, Tarella C; Gruppo Italiano Trapianto di Midollo Osseo (GITMO); Intergruppo Italiano Linfomi (IIL). Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage. Blood. 2008;111: 4004-4013.
  4. Barr PM, Lazarus HM. Follicular non-Hodgkin lymphoma: long-term results of stem-cell transplantation. Curr Opin Oncol. 2008;20:502-508.
  5. Metzner B, Pott C, Müller TH, Gebauer W, Casper J, Kraemer D, Rosien B, Schumann-Binarsch S, Thole R, Köhne CH. Long-term clinical and molecular remissions in patients with follicular lymphoma following high-dose therapy and autologous stem cell transplantation. Ann Oncol. 2013;24(6):1609-1615.
  6. Sebban C, Brice P, Delarue R, Haioun C, Souleau B, Mounier N, Brousse N, Feugier P, Tilly H, Solal-Céligny P, Coiffier B. Impact of rituximab and/or high-dose therapy with autotransplant at time of relapse in patients with follicular lymphoma: a GELA study. J Clin Oncol. 2008;26 (21):3614-3620.
  7. Montoto S, Corradini P, Dreyling M, Ghielmini M, Kimby E, López-Guillermo A, Mackinnon S, Marcus RE, Salles G, Schouten HC, Sureda A, Dreger P. Indications for hematopoietic stem cell transplantation in patients with follicular lymphoma:a consensus project of the EBMT Lymphoma Working Party. Haematologica. 2013;98(7):1014-1021.
  8. Rohatiner AZ, Nadler L, Davies AJ, Apostolidis J, Neuberg D, Matthews J, Gribben JG, Mauch PM, Lister TA, Freedman AS. Myeloablative therapy with autologous bone marrow transplantation for follicular lymphoma at the time of second or subsequent remission: long-term follow-up. J Clin Oncol. 2007;25(18): 2554-2559.
  9. Kornacker M, Stumm J, Pott C, Dietrich S, Süssmilch S, Hensel M, Nickelsen M, Witzens-Harig M, Kneba M, Schmitz N, Ho AD, Dreger P. Characteristics of relapse after autologous stem-cell transplantation for follicular lymphoma: a long-term follow-up. Ann Oncol. 2009;20:722-728.
  10. Hyun SY, Cheong JW, Kim SJ, Min YH, Yang DH, Ahn JS, Lee WS, Ryoo HM, Do YR, Lee HS, Lee JH, Oh SY, Suh C, Yhim HY, Kim JS. High-Dose Etoposide Plus Granulocyte Colony-Stimulating Factor as an Effective Chemomobilization Regimen for Autologous Stem Cell Transplantation in Patients with Non-Hodgkin Lymphoma Previously Treated with CHOP-based Chemotherapy: A Study from the Consortium for Improving Survival of Lymphoma. Biol Blood Marrow Transplant. 2014;20(1):73-79.
  11. Brugger W, Bross KJ, Glatt M, Weber F, Mertelsmann R, Kanz L. Mobilization of tumor cells and hematopoetic progenitor cells into peripheral blood of patients with solid tumors. Blood. 1994;83(3):636-640.
  12. Espigado I, Ríos E, Marín-Niebla A, Carmona M, Parody R, Pérez-Hurtado JM, Márquez FJ, Urbano-Ispizua A. High rate of long-term survival for high-risk lymphoma patients treated with hematopoietic stem cell transplantation as consolidation or salvage therapy. Transplant Proc. 2008;40:3104-3105.
  13. Romero M, Brière J, de Bazelaire C, Lebœuf C, Wang L, Ratajczak P, Sibon D, de Kerviler E, Thieblemont C, Janin A. Aflibercept-mediated early angiogenic changes in aggressive B-cell lymphoma. Cancer Chemother Pharmacol. 2011;68(5):1135-1143.
  14. Baldo P, Rupolo M, Compagnoni A. Interferon-alpha for maintenance of follicular lymphoma. Cochrane Database Syst Rev. 2010;(1):CD004629.
  15. Folkman J, D’Amore PA. Blood vessel formation: what is its molecular basis? Cell. 1996;87:1153-1155.
  16. Ott G, Katzenberger T, Lohr A. Cytomorphologic, immunohistochemical, and cytogenetic profiles of follicular lymphoma: 2 types of follicular lymphoma grade 3. Blood. 2002;99(10):3806-3912.
  17. Schneider M, Othman-Hassan K, Christ B, Wilting J. Lymphangioblasts in the avian wing bud. Dev Dyn. 1999;216:311-319.
  18. Advani RH, Hong F, Horning SJ, Kahl BS, Manola J, Swinnen LJ, Habermann TM, Ganjoo K. Cardiac toxicity associated with bevacizumab (Avastin) in combination with CHOP chemotherapy for peripheral T cell lymphoma in ECOG 2404 trial. Leuk Lymphoma. 2012;53(4):718-720.
  19. Aggarwal D, Srivastava G, Gupta R, Pant L, Krishan G, Singh S. Angiogenesis in Non-Hodgkin’s Lymphoma: An Intercategory Comparison of Microvessel Density. ISRN Hematol. 2012; 2012:943089.
  20. Alduaij W, Illidge T. The future of anti-CD20 monoclonal antibodies: are we making progress? Blood. 2011;117(11):2993-3001.
  21. Blystad AK, Delabie J, Kvaløy S, Holte H, Vålerhaugen H, Ikonomou I, Kvalheim G. Infused CD34 cell dose, but not tumour cell content of peripheral blood progenitor cell grafts, predicts clinical outcome in patients with diffuse large B-cell lymphoma and follicular lymphoma grade 3 treated with high-dose therapy. Br J Haematol. 2004;125(5):605-612.
  22. Tóthová E, Kafková A, Guman T, Stecová N, Fricová M. Efficiency of in vivo purging with autologous stem cell transplantation and monoclonal antibody in B-cell lymphomas. Neoplasma. 2003;50(1):22-25.
  23. Andrade Campos M.MAndrade Campos MM, Montes Limón AE, Grasa JM, Lievano P, Baringo T, Giraldo P. RIT with Y90-Ibritumomab Tiuxetan in Follicular Non-Hodgkin Lymphoma: Evaluation of Recent Outcomes in a Single Institution. J Oncol. 2012;2012:412742.
  24. Ozkan HA, Bal C, Gulbas Z. Chemomobilization with high-dose etoposide and G-CSF results in effective and safe stem cell collection in heavily pretreated lymphoma patients: report from a single institution study and review. Eur J Haematol. 2014;92(5):390-397. doi: 10.1111/ejh.12266
  25. Gyan E, Foussard C, Bertrand P, Michenet P, Le Gouill S, Berthou C, Maisonneuve H, Delwail V, Gressin R, Quittet P, Vilque JP, Desablens B, Jaubert J,Ramée JF, Arakelyan N, Thyss A, Moluçon-Chabrot C, Delépine R, Milpied N, Colombat P, Deconinck E; Groupe Ouest-Est des Leucémies et des Autres Maladies du Sang (GOELAMS). High-dose therapy followed by autologous purged stem cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by the GOELAMS with final results after a median follow-up of 9 years. Blood. 2009;113: 995-1001.
  26. Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA,Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised Response Criteria for Malignant Lymphoma. J Clin Oncol. 2007;25:579-586.
  27. Руководство по гематологии. Под ред. Воробьева А.И. 3-е изд. М.: Ньюдиамед; 2003.
  28. Steffanoni S, Ghielmini M, Moccia A. Chemotherapy and treatment algorithms for follicular lymphoma: a look at all options. Expert Rev Anticancer Ther. 2015;28:1-13.
  29. Нестерова Е.С., Кравченко С.К., Гемджян Э.Г., Магомедова А.У., Капланская И.Б., А.М. Ковригина, Е.А. Барях, Кременецкая А.М. Итоги десятилетнего опыта лечения больных фолликулярной лимфомой. Гематология и трансфузиология. 2012;5:3-8.
  30. Сборник алгоритмов диагностики и протоколов лечения заболеваний системы крови. Под ред. Савченко В.Г. М.: Практика; 2012.
  31. Нестерова Е.С., Кравченко С.К., Гемджян Э.Г., Османов Е.А., Ковригина А.М. Оценка васкуляризации и микроокружения опухолевой ткани при фолликулярной лимфоме. Терапевтический архив. 2013;85(7):57-64.
  32. Нестерова Е.С., Ковригина А.М., Гемджян Э.Г., Магомедова А.У., Барях Е.А., Чернова Н.Г., Марьин Д.С., Гаврилина О.А., Лукина А.Е., Васильева К.С., Кравченко С.К. Опыт применения высокодозной терапии с последующей ауто-ТСКК при фолликулярной лимфоме в первой линии терапии. Гематология и трансфузиология. 2014;59(S1):54-55.
  33. Nesterova ES, Kravchenko SK, Kovrigina AM, Gemdzhian EG, Magomedova AU, Bariakh EA, Vorobyev VI, Iliushkina EA, Mariin DS, Chernova NG, Gavrilina OA, Lukina AE, Savchenko VG. Front-Line High Dose Therapy with Following Autologous Stem Cell Transplantation (ASCT) for Follicular Lymphoma Patients. Blood. 2014;124:5908. http://www.bloodjournal.org/content/124/21/5908
  34. Мангасарова Я.К., Магомедова А.У., Кравченко С.К., Шмаков Р.Г., Барях Е.А., Воробьев В.И., Марьин Д.С., Скидан Н.И., Гемджян Э.Г., Мисюрин А.В., Кременецкая А.М., Воробьев А.И. Восьмилетний опыт лечения агрессивных В-крупноклеточных лимфом средостения. Терапевтический архив. 2013;85(7):50-56.
  35. Kuittinen T, Nousiainen T, Halonen P, Mahlamäki E, Jantunen E. Prediction of mobilisation failure in patients with non-Hodgkin’s lymphoma. Bone Marrow Transplant. 2004;33(9):907-912.

Copyright (c) 2016 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 

Address of the Editorial Office:

  • Novij Zykovskij proezd, 3, 40, Moscow, 125167

Correspondence address:

  • Alabyan Street, 13/1, Moscow, 127055, Russian Federation

Managing Editor:

  • Tel.: +7 (926) 905-41-26
  • E-mail: e.gorbacheva@ter-arkhiv.ru

 

© 2018-2021 "Consilium Medicum" Publishing house


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies