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Investigational strategies in autologous stem cell transplantation for follicular lymphoma

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Abstract

Recent retrospective analyses indicate prolonged survival for patients with follicular lymphoma over the past 25 years, attributed most likely to improved supportive care and sequential application of effective therapies. Encouraging results were obtained from several randomized trials evaluating myeloablative therapy followed by autologous stem cell transplantation (ASCT) as consolidation therapy applied to patients with advanced-stage follicular lymphoma either in first remission or as salvage therapy. However, because of the successful introduction of rituximab to the standard therapeutic repertoire, with its long-term beneficial clinical impact, ASCT must be reevaluated in prospective clinical trials, especially taking into account the potential short- and long-term toxicity associated with high-dose therapy. The concept of in vivo purging before or after ASCT and the introduction of radioimmunotherapy as part of the myeloablative regimen may further improve treatment results, reduce toxicity, and increase applicability. Combination of these novel strategies into a multimodal approach justifies hope that the treatment outcome of patients suffering from follicular lymphoma will be further improved.

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References and Recommended Reading

  1. Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin 2005, 55:74–108.

    PubMed  Google Scholar 

  2. Jemal A, Murray T, Samuels A, et al.: Cancer statistics, 2003. CA Cancer J Clin 2003, 53:5–26.

    Article  PubMed  Google Scholar 

  3. Jaffe ES, Harris NL, Stein H: Tumours of the Haemopoitic and Lymphoid Tissues. Lyon, France: IARC Press; 2001.

    Google Scholar 

  4. Young RC, Longo DL, Glatstein E, et al.: The treatment of indolent lymphomas: watchful waiting v aggressive combined modality treatment. Semin Hematol 1988, 25(Suppl 2):11–16.

    PubMed  CAS  Google Scholar 

  5. Ardeshna KM, Smith P, Norton A, et al.: Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial. Lancet 2003, 362:516–522.

    Article  PubMed  CAS  Google Scholar 

  6. Brice P, Bastion Y, Lepage E, et al.: Comparison in lowtumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d’Etude des Lymphomes Folliculaires. Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol 1997, 15:1110–1117.

    PubMed  CAS  Google Scholar 

  7. Horning SJ: Natural history of and therapy for the indolent non-Hodgkin’s lymphomas. Semin Oncol 1993, 20(Suppl 5):75–88.

    PubMed  CAS  Google Scholar 

  8. Swenson WT, Wooldridge JE, Lynch CF, et al.: Improved survival of follicular lymphoma patients in the United States. J Clin Oncol 2005, 23:5019–5026. This recent retrospective analysis of a large population-based registry reports for the first time prolonged survival of patients with FL over the past 25 years.

    Article  PubMed  Google Scholar 

  9. Freedman AS, Neuberg D, Mauch P, Soiffer RJ, et al.: Longterm follow-up of autologous bone marrow transplantation in patients with relapsed follicular lymphoma. Blood 1999, 94:3325–3333.

    PubMed  CAS  Google Scholar 

  10. Bierman PJ, Vose JM, Anderson JR, et al.: High-dose therapy with autologous hematopoietic rescue for follicular low-grade non-Hodgkin’s lymphoma. J Clin Oncol 1997, 15:445–450.

    PubMed  CAS  Google Scholar 

  11. Apostolidis J, Gupta RK, Grenzelias D, et al.: High-dose therapy with autologous bone marrow support as consolidation of remission in follicular lymphoma: long-term clinical and molecular follow-up. J Clin Oncol 2000, 18:527–536.

    PubMed  CAS  Google Scholar 

  12. van Besien K, Loberiza FR Jr, Bajorunaite R, et al.: Comparison of autologous and allogeneic hematopoietic stem cell transplantation for follicular lymphoma. Blood 2003, 102:3521–3529.

    Article  PubMed  CAS  Google Scholar 

  13. 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, 21:3918–3927. This is the only randomized trial demonstrating significantly improved PFS and OS in a relatively small number of chemosensitive patients with relapsed FL who received ASCT after an initial CHOP-like regimen.

    Article  PubMed  CAS  Google Scholar 

  14. Forstpointner R, Dreyling M, Repp R, et al.: The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 2004, 104:3064–3071. This randomized trial demonstrated the superiority of immunochemotherapy in patients with relapsed FL in terms of improved OS.

    Article  PubMed  CAS  Google Scholar 

  15. Lenz G, Dreyling M, Schiegnitz E, et al.: 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, 104:2667–2674. This randomized trial demonstrated prolonged PFS after myeloablative radiochemotherapy followed by ASCT in first remission for patients with FL.

    Article  PubMed  CAS  Google Scholar 

  16. Deconinck E, Foussard C, Milpied N, et al.: 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 GOELAMS. Blood 2005, 105:3817–3823. Due to the exceeding incidence of secondary fatal cancers in the high-dose group of patients in this randomized trial, the observed improved EFS did not translate into an improved OS for patients treated with myeloablative therapy and ASCT.

    Article  PubMed  CAS  Google Scholar 

  17. Sebban C, Belanger C, Brousse N, et al.: Comparison of CHVP + interferon with CHOP followed by autologous stem cell transplantation with a TBI conditioning regimen in untreated patients with high tumor burden follicular lymphoma: results of the randomized GELF94 trial (G.E.L.A. Study Group). Blood 2003, 102:354a.

    Google Scholar 

  18. Marcus R, Imrie K, Belch A, et al.: CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood 2005, 105:1417–1423. One of the first reports of a randomized trial demonstrating superiority of adding rituximab to conventional chemotherapy for the treatment of advanced-stage FL.

    Article  PubMed  CAS  Google Scholar 

  19. Hiddemann W, Kneba M, Dreyling M, et al.: Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 2005, 106:3725–3732. This large randomized trial not only demonstrated improved response rates and duration of responses by adding rituximab to the CHOP regimen for patients with advanced-stage FL but also showed superior OS despite a relatively short observation time.

    Article  PubMed  CAS  Google Scholar 

  20. Hiddemann W, Forstpointner R, Kneba M et al.: The addition of rituximab to combination chemotherapy with CHOP has a long lasting impact on subsequent treatment in remission in follicular lymphoma but not in mantle cell lymphoma: results of two prospective randomized studies of the German Low Grade Lymphoma Study Group (GLSG). Blood 2004, 104:161a.

    Google Scholar 

  21. Lenz G, Dreyling M, Schiegnitz E, et al.: Moderate increase of secondary hematologic malignancies after myeloablative radiochemotherapy and autologous stem-cell transplantation in patients with indolent lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group. J Clin Oncol 2004, 22:4926–4933. This report confirms the moderately increased risk of secondary hematologic malignancies after high-dose radioimmunotherapy and ASCT for patients with FL in first remission based on a prospective trial.

    Article  PubMed  Google Scholar 

  22. Solal-Celigny P, Roy P, Colombat P, et al.: Follicular lymphoma international prognostic index. Blood 2004, 104:1258–1265.

    Article  PubMed  CAS  Google Scholar 

  23. Buske C, Hoster E, Dreyling M, et al.: The Follicular Lymphoma International Prognostic Index (FLIPI) predicts treatment outcome in patients with advanced stage follicular lymphoma treated front-line with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Blood 2005, 106:272a.

    Google Scholar 

  24. Jacobsen E, Freedman A: B-cell purging in autologous stem-cell transplantation for non-Hodgkin lymphoma. Lancet Oncol 2004, 5:711–717.

    Article  PubMed  CAS  Google Scholar 

  25. Negrin RS, Kusnierz-Glaz CR, et al.: Transplantation of enriched and purged peripheral blood progenitor cells from a single apheresis product in patients with non-Hodgkin’s lymphoma. Blood 1995, 85:3334–3341.

    PubMed  CAS  Google Scholar 

  26. Corradini P, Ladetto M, Zallio F, et al.: Long-term followup of indolent lymphoma patients treated with high-dose sequential chemotherapy and autografting: evidence that durable molecular and clinical remission frequently can be attained only in follicular subtypes. J Clin Oncol 2004, 22:1460–1468.

    Article  PubMed  Google Scholar 

  27. Magni M, Di Nicola M, Devizzi L, et al.: Successful in vivo purging of CD34-containing peripheral blood harvests in mantle cell and indolent lymphoma: evidence for a role of both chemotherapy and rituximab infusion. Blood 2000, 96:864–869.

    PubMed  CAS  Google Scholar 

  28. Galimberti S, Guerrini F, Morabito F, et al.: Quantitative molecular evaluation in autotransplant programs for follicular lymphoma: efficacy of in vivo purging by rituximab. Bone Marrow Transplant 2003, 32:57–63.

    Article  PubMed  CAS  Google Scholar 

  29. Brugger W, Hirsch J, Repp R, et al.: Long term remission in follicular lymphoma (FL) and mantle cell lymphoma (MCL) with rituximab consolidation after high-dose chemotherapy and autologous stem cell transplantation: Extended followup of a multicenter phase II study. Blood 2005, 106:588a.

    Google Scholar 

  30. Johansson L, Carlsson J, Nilsson K: Radiosensitivity of human B-lymphocytic lymphomas in vitro. Int J Radiat Biol Relat Stud Phys Chem Med 1982, 41:411–420.

    PubMed  CAS  Google Scholar 

  31. Safwat A: The role of low-dose total body irradiation in treatment of non-Hodgkin’s lymphoma: a new look at an old method. Radiother Oncol 2000, 56:1–8.

    Article  PubMed  CAS  Google Scholar 

  32. Press OW: Radioimmunotherapy for non-Hodgkin’s lymphomas: a historical perspective. Semin Oncol 2003, 30(Suppl 4):10–21.

    PubMed  CAS  Google Scholar 

  33. Anderson KC, Bates MP, Slaughenhoupt BL, et al.: Expression of human B cell-associated antigens on leukemias and lymphomas: a model of human B cell differentiation. Blood 1984, 63:1424–1433.

    PubMed  CAS  Google Scholar 

  34. Press OW, Appelbaum F, Ledbetter JA, et al.: Monoclonal antibody 1F5 (anti-CD20) serotherapy of human B cell lymphomas. Blood 1987, 69:584–591.

    PubMed  CAS  Google Scholar 

  35. Tedder TF, Boyd AW, Freedman AS, et al.: The B cell surface molecule B1 is functionally linked with B cell activation and differentiation. J Immunol 1985, 135:973–979.

    PubMed  CAS  Google Scholar 

  36. Gopal AK, Gooley TA, Maloney DG, et al.: High-dose radioimmunotherapy versus conventional high-dose therapy and autologous hematopoietic stem cell transplantation for relapsed follicular non-Hodgkin lymphoma: a multivariable cohort analysis. Blood 2003, 102(7):2351–2357.

    Article  PubMed  CAS  Google Scholar 

  37. Press OW, Eary JF, Gooley T, et al.: phase I/II trial of iodine-131-tositumomab (anti-CD20), etoposide, cyclophosphamide, and autologous stem cell transplantation for relapsed B-cell lymphomas. Blood 2000, 96:2934–2942.

    PubMed  CAS  Google Scholar 

  38. Vose JM, Bierman PJ, Enke C, et al.: Phase I trial of iodine-131 tositumomab with high-dose chemotherapy and autologous stem-cell transplantation for relapsed non-Hodgkin’s lymphoma. J Clin Oncol 2005, 23:461–467.

    Article  PubMed  CAS  Google Scholar 

  39. Flinn IW, Kahl BS, Frey E, et al.: Dose finding trial of yttrium 90 (90Y) ibritumomab tiuxetan with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory B-cell non-Hodgkins lymphoma (NHL). Blood 2004, 104:169a.

    Google Scholar 

  40. Nademanee A, Forman S, Molina A, et al.: A phase 1/2 trial of high-dose yttrium-90-ibritumomab tiuxetan in combination with high-dose etoposide and cyclophosphamide followed by autologous stem cell transplantation in patients with poor-risk or relapsed non-Hodgkin lymphoma. Blood 2005, 106:2896–2902.

    Article  PubMed  CAS  Google Scholar 

  41. Winter JN, Inwards DJ, Spies S: 90 Y ibritumomab tiuxetan (Zevalin, 90YZ) doses higher than.4 mCi/kg may be safely combined with high-dose BEAM and autotransplant: the role of dosimetry. Blood 2004, 104:329a.

    Google Scholar 

  42. Krishnan AY, Nademanee A, Forman SJ, et al.: The outcome of ZBEAM, a regimen combining 90Y ibritumomab tiuxetan with high dose chemotherapy in elderly patients with non-Hodgkin’s lymphoma [abstract]. Proc ASCO 2005, 23:576s.

    Google Scholar 

  43. Vanazzi A, Ferrucci P, Ferrari M, et al.: High dose Zevalin (90yttrium ibritumomab tiuxetan) treatment with PBSC support in refractory-resistant NHL patients: preliminary results of a phase I/II study. Blood 2005, 106:146a.

    Google Scholar 

  44. Peniket AJ, Ruiz de Elvira MC, Taghipour G, et al.: An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedurerelated mortality rate than autologous transplantation. Bone Marrow Transplant 2003, 31:667–678.

    Article  PubMed  CAS  Google Scholar 

  45. Khouri IF, Saliba RM, Hosing C, et al.: Autologous stem cell (AUTO) vs. non-myeloablative allogeneic transplantation (NMT) after high-dose rituximab (HD-R) -containing conditioning regimens for relapsed chemosensitive follicular lymphoma (FL). Blood 2005, 106:110.

    Article  CAS  Google Scholar 

  46. Micallef IN, Lillington DM, Apostolidis J, et al.: Therapyrelated myelodysplasia and secondary acute myelogenous leukemia after high-dose therapy with autologous hematopoietic progenitor-cell support for lymphoid malignancies. J Clin Oncol 2000, 18:947–955.

    PubMed  CAS  Google Scholar 

  47. Howe R, Micallef IN, Inwards DJ, et al.: Secondary myelodysplastic syndrome and acute myelogenous leukemia are significant complications following autologous stem cell transplantation for lymphoma. Bone Marrow Transplant 2003, 32:317–324.

    Article  PubMed  CAS  Google Scholar 

  48. Nickenig C, Dreyling M, Hoster E, et al.: MCP (mitoxantrone/ chlorambucil/prednisolone) chemotherapy impairs the subsequent collection of stem cells in comparison to CHOP induction in patients with indolent lymphomas: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). Blood 2005, 106:931a.

    Google Scholar 

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Correspondence to Christian Buske MD.

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Weigert, O., Dreyling, M., Unterhalt, M. et al. Investigational strategies in autologous stem cell transplantation for follicular lymphoma. Curr Oncol Rep 8, 368–375 (2006). https://doi.org/10.1007/s11912-006-0060-2

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