Role of high-dose chemotherapy with hemopoietic stem cell transplantation in patients with non-Hodgkin's lymphomas
https://doi.org/10.17650/1818-8346-2006-0-1-2-86-96
Abstract
High-dose chemotherapy (HDC) with autologous or allogenic hemopoietic stem cell transplantation (SCT) is successfully used in refractory, relapsed or high-risk primary aggressive non-Hodgkin's lymphomas (NHL). Results on HDC employing in follicular lymphoma, is inconclusive. Recent studies has suggested that com- bining of anti-CD20 (rituximab) with HDC (HDC-R) may successfully eliminate minimal residual disease, further delaying or preventing disease relapse and potentially extending the duration of survival after autologous SCT in patient with aggressive B-cell lymphomas. The paper discusses recent dates on HDC-R treatment strategy and presents the author's own data on the use of HDC with autologous SCT in a group of 50 patients with relapsed and primary resistant NHL (22 of them received rituximab at different stages of treatment - remission induction, stem cell collection, posttransplantation period). In all patients receiving high- dose therapy, 5-year overall survival was 40.3% and 5-year relapse-free survival was 77.5%. 5-year overall survival was 52% in patients with the B-cell pheno- type treated with HDC plus rituximab, and 21% in those treated with HDC only (p = 0.014). Treatment toxicity was comparable in both groups.
About the Authors
V. V. Ptushkin
N.N. Blokhin Russian Cancer Research Cancer, Russian Academy of Medical Sciences
Russian Federation
Russian Federation
Moscow
N. V. Zhukov
N.N. Blokhin Russian Cancer Research Cancer, Russian Academy of Medical Sciences
Russian Federation
Russian Federation
Moscow
S. V. Minenko
N.N. Blokhin Russian Cancer Research Cancer, Russian Academy of Medical Sciences
Russian Federation
Russian Federation
Moscow
A. Y. Popov
N.N. Blokhin Russian Cancer Research Cancer, Russian Academy of Medical Sciences
Russian Federation
Russian Federation
Moscow
D. M. Mheidze
N.N. Blokhin Russian Cancer Research Cancer, Russian Academy of Medical Sciences
Russian Federation
Russian Federation
Moscow
L. Y. Andreeva
N.N. Blokhin Russian Cancer Research Cancer, Russian Academy of Medical Sciences
Russian Federation
Russian Federation
Moscow
References
1. Frei E. III, Canellos G.P. Dose, a critical factor in cancer chemotherapy. Am J Med 1986;69:585.
2. Gorin N.C., Gale R.P., Armitage J.O. Autologous bone marrow transplant, different indication in Europe and North America. Lancet 1989;2:312–8.
3. [No authors listed]. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. The Non-Hodgkin’s Lymphoma Classification Project. Blood 1997;89(11):3909–18.
4. Thomas D.A., O'Brien S., Cortes J. et al. Outcome with the hyper-CVAD regimens in lymphoblastic lymphoma. Blood 2004;104(6):1624–30.
5. Hoelzer D., Gokbuget N., Digel W. et al. Outcome of adult patients with T-lymphoblastic lymphoma treated according to protocols for acute lymphoblastic leukemia. Blood 2002;99(12):4379–85.
6. van Imhoff G.W., van der Holt B., MacKenzie M.A. et al. Short intensive sequential therapy followed by autologous stem cell transplantation in adult Burkitt, Burkitt-like and lymphoblastic lymphoma. Leukemia 2005;19(6):945–52.
7. Bouabdallah R., Xerri L., Bardou V.J. et al. Role of induction chemotherapy and bone marrow transplantation in adult lymphoblastic lymphoma, a report on 62 patients from a single center. Ann Oncol 1998;9(6):619–25.
8. van Besien K.W., Mehra R.C., Giralt S.A. et al. Allogeneic bone marrow transplantation for poor-prognosis lymphoma: response, toxicity and survival depend on disease histology. Am J Med. 1996; 100(3):299–307.
9. Levine J.E., Harris R.E., Loberiza F.R. et al. A comparison of allogeneic and autologous bone marrow transplantation for lymphoblastic lymphoma. Blood 2003;101(7):2476–82.
10. Peniket A.J., Ruiz de Elvira M.C., 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 procedure-related mortality rate than autologous transplantation. Bone Marrow Transplant 2003;31(8):667–78.
11. Ladenstein R., Pearce R., Hartmann O. et al. High-dose chemotherapy with autologous bone marrow rescue in children with poor-risk burkitt's lymphoma: a report from the European Lymphoma Bone Marrow Transplantation Registry. Blood 1997;90(8):2921–30.
12. Pfreundschuh M., Trumper L., Kloess M. et al. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas, results of the NHL-B2 trial of the DSHNHL. Blood 2004;104(3):634–41.
13. Feugier P., van Hoof A., Sebban C. et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma, a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol 2005;23(18):4117–26.
14. Fisher R.I., Gaynor E.R., Dahlberg S. et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med 1993;328(14):1002–6.
15. Maloney D.G. et al. The anti-tumor effect of monoclonal anti-CD20 antibody (mAb) therapy includes direct antiproliferative activity and induction of apoptosis in CD20 positive non-Hodgkin’s lymphoma (NHL) cell lines. Blood 1996;88 (Suppl 1): 637a (abstr 2535).
16. Cabanillas F., Hagemeister F.B., Bodey J.P., Freireich E.J. IMVP-16: an effective regimen for patients with lymphoma who have relapsed after initial combination chemotherapy. Blood 1982;60(3):693–7.
17. Velasquez E., Hagemeister F., Mclaughlin P. E-SHAP, an effective treatment for refractory and relapsing lymphoma. A long follow up. J Clin Oncol 1992;11:abstr 326.
18. Gulati S.C., Shank B., Black P. et al. Autologus bone marrow transplantation for patients with poor prognostic lymphoma. JClin Oncol 1988;6(8):1303–13.
19. Tura S. , Mazza P., Cherlizoni F. et al. High-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) in previously untreated nonHodgkin’s lymphoma. Scand J Haematol 1986;37(4):347–52.
20. Gianni A.M., Bregni M., Siena S. et al. High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma. N Engl J Med 1997;336(18):1290–7.
21. Schmitz N., Kloess M., Reiser M. et al. Four versus six courses of a dose-escalated cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen plus etoposide (megaCHOEP) and autologous stem cell transplantation: early dose intensity is crucial in treating younger patients with poor prognosis aggressive lymphoma. Cancer 2006;106(1):136–45.
22. Glass B., Kloess M., Reiser M. et al. Repetitive high dose therapy followed by autologous stem cell transplantation (Mega CHOEP) for primary treatment of aggressive NHK: the impact of rituximab on outcome and toxicity. Bone Marrow Transplant 2006;37 (Suppl 1):S26 (abstr 236).
23. Haioun C., Lepage E., Gisselbrecht C. et al. Comparison of autologous bone marrow transplantation with sequential chemotherapy for intermediate-grade and high-grade non-Hodgkin’s lymphoma in first complete remission: a study of 464 patients. Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol 1994;12(12):2543–451.
24. Haioun C., Lepage E., Gisselbrecht C. et al. Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin’s lymphoma: final analysis of the prospective LNH87-2 Protocol – a groupe d’Etude des lymphomes de l’Adulte study. J Clin Oncol 2000;18(16):3025–30.
25. Gherlinzoni F., Martelli M., Tura S. Early autologous stem cell transplantation (ASCT) versus conventional first line chemotherapy in high-risk aggressive nonHodgkin’s lymphoma (NHL): an Italian multicenter randomized trial. Blood 2000;96(11):481a.
26. Verdonck L.F., van Putten W.L.J., Hagenbeek A. et al. Comparison of CHOP chemotherapy with autologous bone marrow transplantation for slowly responding patients with aggressive nonHodgkin’s lymphoma. N Engl J Med 1995;332(16):1045–51.
27. Philip T., Guglielmi C., Hagenbeek A. et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma. N Engl J Med 1995;333(23):1540–5.
28. Philip T., Armitage J.O., Spitzer G. et al. High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high grade non-Hodgkin’s lymphoma. N Engl J Med 1987;316(24):1493–8.
29. Vose J.M., Zhang M.J., Rowlings P.A. et al. Autologous transplantation for diffuse aggressive non-Hodgkin's lymphoma in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry. J Clin Oncol 2001;19(2):406–13.
30. Popat U., Przepiork D., Champlin R. et al. High-dose chemotherapy for relapsed and refractory diffuse large B-cell lymphoma: mediastinal localization predicts for a favorable outcome. J Clin Oncol 1998;16(1):63–9.
31. Deconinck E., Lamy T., Foussard C. et al. Autologous stem cell transplantation for anaplastic large-cell lymphomas: results of a prospective trial. Br J Haematol 2000;109(4):736–42.
32. Olavarria T., Child F., Woolford A. et al. T-cell depletion and autologous stem cell transplantation in the management of tumor stage mycosis fungoides with peripheral blood involvement. Br J Haematol 2001;114(3):624–31.
33. Bierman P.J., Sweetenham J.W., Loberiza F.R. Jr. et al. Syngeneic hematopoietic stem-cell transplantation for non-Hodgkin’s lymphoma: a comparison with allogeneic and autologous transplantation – The Lymphoma Working Committee of the International Bone Marrow Transplant Registry and the European Group for Blood and Marrow Transplantation. J Clin Oncol 2003;21(20):3744–53.
34. Scott B.L., Sandmaier B.M., Storer B. et al. Myeloablative vs nonmyeloablative allogeneic transplantation for patients with myelodysplastic syndrome or acute myelogenous leukemia with multilineage dyspeasia: a retrospective analysis. Leukemia 2006;20(1):128–35.
35. Hanania E.G., Kavanagh J., Hortobagyi G. et al. Recent advances in the application of gene therapy to human disease. Am J Med 1995;99(5):537–52.
36. Sharp J.G., Kessinger A., Mann S. et al. Outcome of high-dose therapy and autologous transplantation in nonHodgkin's lymphoma based on the presence of tumor in the marrow or infused hematopoietic harvest. J Clin Oncol 1996;14(1):214–9.
37. Demirkazik A., Kessinger A., Armitage J. et al. Progenitor and lymphoma cells in blood stem cell harvests: impact on survival following transplantation. Bone Marrow Transplant 2001;28(2):207–12.
38. Gribben J.G., Freedman A.S., Neuberg D. et al. Immunologic purging of marrow assessed by PCR before autologous bone marrow transplantation for Bcell lymphoma. N Engl J Med 1991;325(22):1525–33.
39. Schouten H.C., 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):3918–27.
40. Hahn T., Wolff S.N., Cruczman M. et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of diffuse large cell B-cell non-Hodgkin's lymphoma: an evidencebased review. Biol Blood Marrow Transplant 2001;7(6):308–31.
41. Spaepen K., Stroobants S., Dupont P. et al. Prognostic value of positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose ([18F]FDG) after first-line chemotherapy in non-Hodgkin’s lymphoma: is [18F]FDG PET a valid alternative to conventional diagnostic methods? J Clin Oncol 2001;19(2):414–41.
42. Kostakoglu L., Coleman M., Leonard J.P. et al. PET predicts prognosis after one cycle of chemotherapy in aggressive lymphoma and Hodgkin’s disease. J Nuc Med 2002;43(8):1018–27.
43. Lossos I.S., Czerwinski D.K., Alizadeh A.A. et al. Prediction of survival in diffuse large B-cell lymphoma based on the expression of six genes. N Engl J Med 2004;350(18):1828–37.
44. Alizadeh A.A., Eisen M.B., Davis R.E. et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000;403(6769):503–11.
45. Moskowitz C.H., Kewelramani T., Hamlin P. et al. The importance of molecular phenotype in predicting overall survival in patients with relapsed or primary refractory DLBCL treated with second line chemotherapy and ASCT. Blood 2004;104:7a.
46. Vose J.M., Bierman P.J., Lynch J.C. et al. Autologous transplant event-free survival (EFS) following failure of CHOPrituximab (CHOP-R) or diffuse large Bcell lymphoma (DLBCL) is the same as the EFS following failure of CHOP alone. Blood 2004;104:254a.
47. Magni M., Di Nicola M., Devizzi L. et al. Successful in vivo purging of CD34containing peripheral blood harvests in mantle cell and indolent lymphoma: evidence for a role of both chemotherapy and rituximab infusion. Blood 2000;96(3):864–9.
48. Moskowitz C.H., Bertino J.R., Glassman J.R. et al. Ifosfamide, carboplatin, and etoposide, a highly effective cytoreduction and peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with nonHodgkin's lymphoma. J Clin Oncol 1999;17(12):3776–85.
49. Prince H.M., Imrie K., Crump M. et al. The role of intensive therapy and autologous blood and marrow transplantation for chemotherapy-sensitive relapsed and primary refractory non-Hodgkin's lymphoma, identification of major prognostic groups. Br J Haematol 1996;92(4):880–9.
50. Kewalramani T., Zelenetz A.D., Nimer S.D. et al. Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood 2004;103(10):3684–8.
51. Horwitz S.M., Negrin R.S., Blume K.G. et al. Rituximab as adjuvant to highdose therapy and autologous hematopoietic cell transplantation for aggressive non-Hodgkin lymphoma. Blood 2004;103(3):777–83.
52. Hoerr A., Gao F., Hidalgo J. et al. Effects of pretransplantation treatment with rituximab on outcomes of autologous stem-cell transplantation for nonHodgkin's lymphoma. J Clin Oncol 2004;22(22):4561–6.
53. Khouri I.F., Saliba R.M., Hosing C. et al. Concurrent administration of highdose rituximab before and after autologous stem-cell transplantation for relapsed aggressive B-cell non-hodgkin’s lymphomas. J Clin Oncol 2005;23(10):2240–7.
54. Птушкин В.В., Жуков Н.В., Миненко С.В. и др. Высокодозная химиотерапия с трансплантацией аутологичных клеток-предшественников гемопоэза и применением ритуксимаба (мабтера) при неходжкинских лимфомах. Соврем онкол 2006;10(3):84–7.
55. 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(4):1417–23.
56. 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(9):2667–74.
57. 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(10):3817–23.
58. Pettengell R. Autologous stem cell transplantation in follicular nonHodgkin's lymphoma. Bone Marrow Transplant 2002;29 (Suppl 1):S1–4.
59. Van Besien K. Autologous and allogeneic stem cell transplantation in follicular lymphoma. Transfus Apher Sci 2005;32(1):45–53.
60. Mangel J., Buckstein R., Imrie K. et al. Pharmacokinetic study of patients with follicular or mantle cell lymphoma treated with rituximab as «in vivo purge» and consolidative immunotherapy following autologous stem cell transplantation. Ann Oncol 2003;14(5):758–65.
61. Ladetto M., Zallio F., Vallet S. et al. Concurrent administration of high-dose chemotherapy and rituximab is a feasible and effective chemo/immunotherapy for patients with high-risk non-Hodgkin's lymphoma. Leukemia 2001;15(12):1941–9.
62. Romaguera J.E., Fayad L., Rodriguez M.A. et al. High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine. J Clin Oncol 2005;23(28):7013–23.
63. Lenz G., Dreyling M., Hoster E. et al. Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol 2005;23(9):1984–92.
64. Dreyling M., Lenz G., Hoster E. et al. Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network. Blood 2005;105(7):2677–84.
65. Gianni A.M., Magni M., Martelli M. et al. Long-term remission in mantle cell lymphoma following high-dose sequential chemotherapy and in vivo rituximabpurged stem cell autografting (R-HDS regimen). Blood 2003;102(2):749–55.
66. Verdonck L.F., Dekker A.W., Lokhorst H.M. et al. Allogeneic versus autologous bone marrow transplantation for refractory and recurrent low-grade non-Hodgkin's lymphoma. Blood 1997;90(10):4201–5.
Review
For citations:
Ptushkin V.V., Zhukov N.V., Minenko S.V., Popov A.Y., Mheidze D.M., Andreeva L.Y. Role of high-dose chemotherapy with hemopoietic stem cell transplantation in patients with non-Hodgkin's lymphomas. Oncohematology. 2006;(1-2):86-96. (In Russ.) https://doi.org/10.17650/1818-8346-2006-0-1-2-86-96
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