Vol 52, No 4 (2021)
Review article
Published online: 2021-08-31

open access

Page views 403
Article views/downloads 562
Get Citation

Connect on Social Media

Connect on Social Media

Autologous stem cell transplantation in lymphomas: current indications

Piotr Rzepecki1
Acta Haematol Pol 2021;52(4):225-233.

Abstract

Hematopoietic stem cell transplantation is an established curative treatment for a number of conditions including malignant hematologic diseases and non-malignant congenital and acquired disorders involving the hematopoietic system and some types of solid tumors, e.g. germ cell tumors and soft tissue sarcomas. Hodgkin’s disease and non-Hodgkin lymphomas can be treated and, in a large number of cases cured, by first-line chemotherapy or radiotherapy. Unlike many other malignancies, relapse is not uniformly fatal but the treatment is usually markedly myelotoxic with the high doses of chemotherapy (HDC) used in relapse. Hematopoietic reconstitution with either autologous marrow or peripheral stem cells post-chemotherapy has made HDC relatively safe, with mortality rates as low as 2% in some centers. The choice of conditiong regimen has traditionally been based on institutional experience, and several regimens are considered standard and routinely used for patients with all histologies of lymphoma. Each HDC regimen is associated with its own unique toxicities, based on the individual agents or modalities used. Novel targeted and immunotherapy approaches, including chimeric antigen receptor T-cell therapy, are currently being studied in clinical trials with promising early results, so the role of autologous stem cell transplantation in the treatment of lymphomas could be changed. The current clinical indications for HDC followed by autologous hematopoietic stem cell transplantation in lymphomas management for patients with a bad prognosis (as a consolidation therapy) or relapsed/refractory disease are reviewed in this paper.

Article available in PDF format

View PDF Download PDF file

References

  1. Matasar MJ, Luminari S, Barr PM, et al. Follicular lymphoma: recent and emerging therapies, treatment strategies, and remaining unmet needs. Oncologist. 2019; 24(11): e1236–e1250.
  2. Marcus R, Davies A, Ando K, et al. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017; 377(14): 1331–1344.
  3. van Oers MHJ, Klasa R, Marcus RE, et al. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006; 108(10): 3295–3301.
  4. Jiménez-Ubieto A, Grande C, Caballero D, et al. Autologous stem cell transplantation for follicular lymphoma: favorable long-term survival irrespective of pretransplantation rituximab exposure. Biol Blood Marrow Transplant. 2017; 23(10): 1631–1640.
  5. Jiménez-Ubieto A, Grande C, Caballero D, et al. GELTAMO (Grupo Español de Linfomas y Trasplantes de Médula Ósea) Cooperative Study Group. Autologous stem cell transplantation may be curative for patients with follicular lymphoma with early therapy failure who reach complete response after rescue treatment. Hematol Oncol. 2018; 36(5): 765–772.
  6. Casulo C, Friedberg JW, Ahn KW, et al. Autologous transplantation in follicular lymphoma with early therapy failure: a National LymphoCare Study and Center for International Blood and Marrow Transplant Research Analysis. Biol Blood Marrow Transplant. 2018; 24(6): 1163–1171.
  7. Jurinovic V, Metzner B, Pfreundschuh M, et al. Autologous stem cell transplantation for patients with early progression of follicular lymphoma: a follow-up study of 2 randomized trials from the German Low Grade Lymphoma Study Group. Biol Blood Marrow Transplant. 2018; 24(6): 1172–1179.
  8. Ladetto M, De Marco F, Benedetti F, et al. 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(8): 4004–4013.
  9. Lenz G, Dreyling M, Schiegnitz E, et al. German Low-Grade Lymphoma Study Group. Myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission prolongs progression-free survival in follicular lymphoma: results of a prospective, randomized trial of the German Low-Grade Lymphoma Study Group. Blood. 2004; 104(9): 2667–2674.
  10. González-Barca E, Fernández de Sevilla A, Domingo-Claros A, et al. Autologous stem cell transplantation (ASCT) with immunologically purged progenitor cells in patients with advanced stage follicular lymphoma after early partial or complete remission: toxicity, follow-up of minimal residual disease and survival. Bone Marrow Transplant. 2000; 26(10): 1051–1056.
  11. Schouten HC, Qian W, Kvaloy S, et al. High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: results from the randomized European CUP trial. J Clin Oncol. 2003; 21(21): 3918–3927.
  12. Pettengell R, Uddin R, Boumendil A, et al. Rituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma: a prospective randomized trial from the lymphoma working party of the European group for blood and marrow transplantation. J Clin Oncol. 2013; 31(13): 1624–1630.
  13. Visani G, Stefani PM, Capria S, et al. Bendamustine, etoposide, cytarabine, melphalan, and autologous stem cell rescue produce a 72% 3-year PFS in resistant lymphoma. Blood. 2014; 124(19): 3029–3031.
  14. Shimoni A, Avivi I, Rowe JM, et al. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012; 118(19): 4706–4714.
  15. Riedell PA, Bishop MR. Post-autologous transplant maintenance therapies in lymphoma: current state and future directions. Bone Marrow Transplant. 2018; 53(1): 11–21.
  16. Robinson S. Follicular lymphoma. In: Carreras E, Dufour C, Mohty M, Kröger N. ed. The EBMT Handbook. Hematopoietic Stem Cell Transplantation and Cellular Therapies. Springer Open, Cham 2019: 621–626.
  17. Sureda A, Bader P, Cesaro S, et al. Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015. Bone Marrow Transplant. 2015; 50(8): 1037–1056.
  18. Kuruvilla J. The role of autologous and allogeneic stem cell transplantation in the management of indolent B-cell lymphoma. Blood. 2016; 127(17): 2093–2100.
  19. Ansell SM. Hodgkin lymphoma: a 2020 update on diagnosis, risk-stratification, and management. Am J Hematol. 2020; 95(8): 978–989.
  20. Federico M, Bellei M, Brice P, et al. EBMT/GISL/ANZLG/SFGM/GELA Intergroup HD01 Trial. High-dose therapy and autologous stem-cell transplantation versus conventional therapy for patients with advanced Hodgkin's lymphoma responding to front-line therapy. J Clin Oncol. 2003; 21(12): 2320–2325.
  21. LaCasce AS. Treating Hodgkin lymphoma in the new millennium: relapsed and refractory disease. Hematol Oncol. 2019; 37 Suppl 1: 87–91.
  22. Moskowitz CH, Walewski J, Nademanee A, et al. AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015; 385(9980): 1853–1862.
  23. Merryman RW, Redd RA, Nishihori T, et al. Autologous stem cell transplantation after anti-PD-1 therapy for multiply relapsed or refractory Hodgkin lymphoma. Blood Adv. 2021; 5(6): 1648–1659.
  24. Moskowitz AJ. Practical treatment approach for angioimmunoblastic T-cell lymphoma. J Oncol Pract. 2019; 15(3): 137–143.
  25. Laribi K, Alani M, Truong C, et al. Recent advances in the treatment of peripheral T-cell lymphoma. Oncologist. 2018; 23(9): 1039–1053.
  26. Zain JM. Aggressive T-cell lymphomas: 2019 updates on diagnosis, risk stratification, and management. Am J Hematol. 2019; 94(8): 929–946.
  27. Rogers AM, Brammer JE. Hematopoietic cell transplantation and adoptive cell therapy in peripheral T cell lymphoma. Curr Hematol Malig Rep. 2020; 15(4): 316–332.
  28. Dietrich S. Mantle cell lymphoma. In: Carreras E, Dufour C, Mohty M, Kröger N. ed. The EBMT Handbook. Hematopoietic Stem Cell Transplantation and Cellular Therapies. Springer Open, Cham 2019: 643–646.
  29. Maddocks K. Update on mantle cell lymphoma. Blood. 2018; 132(16): 1647–1656.
  30. Le Gouill S, Thieblemont C, Oberic L, et al. LYSA Group. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017; 377(13): 1250–1260.
  31. Schmitz N, Stelljes M, Bazarbachi A. Diffuse large B-cell lymphoma. In: Carreras E, Dufour C, Mohty M, Kröger N. ed. The EBMT Handbook. Hematopoietic Stem Cell Transplantation and Cellular Therapies. Springer Open, Cham 2019: 633–642.
  32. Tilly H, Gomes da Silva M, Vitolo U, et al. ESMO Guidelines Committee. Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015; 26(Suppl 5): v116–v125.
  33. Gouill Sle, Milpied N, Buzyn A, et al. Allogeneic stem cell transplantation (allo-SCT) in T-cell lymphomas: a French national survey from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC). J Clin Oncol. 2007; 25(18_suppl): 8095–8095.
  34. Chiappella A, Martelli M, Angelucci E, et al. Rituximab-dose-dense chemotherapy with or without high-dose chemotherapy plus autologous stem-cell transplantation in high-risk diffuse large B-cell lymphoma (DLCL04): final results of a multicentre, open-label, randomised, controlled, phase 3 study. Lancet Oncol. 2017; 18(8): 1076–1088.
  35. Schmitz N, Nickelsen M, Ziepert M, et al. German High-Grade Lymphoma Study Group (DSHNHL). Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1). Lancet Oncol. 2012; 13(12): 1250–1259.
  36. Stiff PJ, Unger JM, Cook JR, et al. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013; 369(18): 1681–1690.
  37. Schmitz N, Ziepert M, Vitolo U, et al. German High-Grade Non-Hodgkin’s Lymphoma Study Group, Fondazione Italiana Linfomi. The role of myeloablation for lymphoma. N Engl J Med. 2014; 370(6): 574–575.
  38. Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017; 130(16): 1800–1808.
  39. Gisselbrecht C, Schmitz N, Mounier N, et al. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol. 2012; 30(36): 4462–4469.
  40. Ansell SM, Stenson M, Habermann TM, et al. Cd4+ T-cell immune response to large B-cell non-Hodgkin's lymphoma predicts patient outcome. J Clin Oncol. 2001; 19(3): 720–726.
  41. Porrata LF, Litzow MR, Markovic SN. Immune reconstitution after autologous hematopoietic stem cell transplantation. Mayo Clin Proc. 2001; 76(4): 407–412.
  42. Armand P, Nagler A, Weller EA, et al. Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: results of an international phase II trial. J Clin Oncol. 2013; 31(33): 4199–4206.
  43. Casasnovas RO, Ysebaert L, Thieblemont C, et al. FDG-PET-driven consolidation strategy in diffuse large B-cell lymphoma: final results of a randomized phase 2 study. Blood. 2017; 130(11): 1315–1326.
  44. Hubel K, Montoto S. Other T- and B-aggressive lymphomas and lymphomas associated with HIV. In: Carreras E, Dufour C, Mohty M, Kröger N. ed. The EBMT Handbook. Hematopoietic Stem Cell Transplantation and Cellular Therapies. Springer Open, Cham 2019: 647–652.
  45. Illerhaus G, Marks R, Ihorst G, et al. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol. 2006; 24(24): 3865–3870.
  46. Erkurt MA, Berber I, Tekgündüz E, et al. Primary central nervous system lymphoma in daily practice and the role of autologous stem cell transplantation in relapsed disease: A retrospective multicenter study. Transfus Apher Sci. 2016; 54(1): 80–84.
  47. Chen YB, Lane AA, Logan B, et al. Impact of conditioning regimen on outcomes for patients with lymphoma undergoing high-dose therapy with autologous hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2015; 21(6): 1046–1053.