Management of relapsed-refractory diffuse large B cell lymphoma

Lalit S. Raut; Prantar P. Chakrabarti

doi:10.4103/2278-330X.126531

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Review Article

03 (

); 066-070

doi:

10.4103/2278-330X.126531

Management of relapsed-refractory diffuse large B cell lymphoma

Lalit S. Raut^1,, Prantar P. Chakrabarti¹

1 Institute of Haematology and Transfusion Medicine, Medical College and Hospital, Kolkata, West Bengal

*Corresponding author: Dr. Lalit Raut. lalitraut76@yahoo.co.in

Published: 2020-12-31

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Abstract

Relapsed-Refractory Diffuse Large B Cell Lymphoma (RR DLBCL), which accounts for approximately one-third of patients with DLBCL, remains a major cause of morbidity and mortality. Managing RR DLBCL continues to be a challenge to the treating hemato-oncologist. Salvage high-dose chemotherapy followed by autologous stem cell transplantation is the standard of care for chemosensitive relapses in DLBCL. Various salvage regimens are available, but the quest for an optimal regimen continues. The addition of rituximab to the salvage regimen has improved the outcome of RR DLBCL. Several pertinent issues regarding the management of RR DLBCL are discussed in this short review.

Keywords

Acknowledgment

All IHTM Staff

References

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Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: Evolving concepts and practical applications. Blood 2011;117:5019-32.
Lenz G, Wright G, Dave SS, Xiao W, Powell J, Zhao H, et al. Stromal gene signatures in large B cell lymphomas. N Engl J Med 2008;359:2313-23.
Lenz G, Staudt LM. Aggressive lymphomas. N Engl J Med 2010;362:1417-29.
Garvin AJ, Simon RM, Osborne CK, Merrill J, Young RC, Berard CW. An autopsy study of histologic progression in non Hodgkin′s lymphomas: 192 cases from the National Cancer Institute. Cancer 1983;52:393-8.
Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-b-cell lymphoma. N Engl J Med 2002;346:235-42.
Perry AR, Goldstone AH. High-dose therapy for diffuse large-cell lymphoma in ﬁrst remission. Ann Oncol 1998;9(Suppl 1):S9-14.
Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, et al. Comparison of a Standard Regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin′s Lymphoma N Engl J Med 1993;328:1002-6.
Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, et al. Report of an international workshop to standardize response criteria for non-Hodgkin lymphomas. J Clin Oncol 1999;17:1244-53.
Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: A randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol 2006;7:379-91.
Hamlin PA, Zelenetz AD, Kewalramani T, Qin J, Satagopan JM, Verbel D, et al. Age-adjusted International Prognostic Index predicts autologous stem cell transplantation outcome for patients with relapsed or primary refractory diffuse large B-cell lymphoma. Blood 2003;102:1989-96.
Weeks JC, Yeap BY, Canellos GP, Shipp MA. Value of follow-up procedures in patients with large-cell lymphoma who achieve a complete remission. J Clin Oncol 1991;9:1196-203.
Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy sensitive non-Hodgkin lymphoma. N Engl J Med 1995;333:1540-5.
Moskowitz CH, Bertino JR, Glassman JR, Hedrick EE, Hunte S, Coady-Lions N, et al. Ifosfamide, carboplatin and etoposide: A highly effective cyto-reduction and peripheral blood progenitor cell mobilization regimen for transplant-eligible patients with non-Hodgkins lymphoma. J Clin Oncol 1999;17:3776-85.
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Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, et al. ESHAP - an effective chemotherapy regimen in refractory and relapsing lymphoma: A 4-year follow-up study. J Clin Oncol 1994;12:1169-76.
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Hicks L, Buckstein R, Mangel J, Piliotis E, Imrie K, Cheung MC, et al. Rituximab increases response to ESHAP in relapsed, refractory, and transformed aggressive B-cell lymphoma. Blood 2006;108:Abstract 3067.
Zelenetz AD, Hamlin P, Kewalramani T, Yahalom J, Nimer S, Moskowitz CH. Ifosfamide, carboplatin, etoposide (ICE) based second line chemotherapy for the management of relapsed and refractory aggressive non Hodgkin′s lymphoma. Ann Oncol 2003;14(Suppl 1):i5-10.
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Thieblemont C, Briere J, Mounier N, Voelker HU, Cuccuini W, Hirchaud E, et al. The Germinal center/activated B-cell subclassiﬁcation has a prognostic impact for response to salvage therapy in relapsed/refractory diffuse large B-cell lymphoma: A bio-CORAL study. J Clin Oncol 2011;29:4079-87.
Rodriguez J, Caballero MD, Gutierrez A, Solano C, Arranz R, Lahuerta JJ, et al. Autologous stem-cell transplantation in diffuse large B-cell non-Hodgkin′s lymphoma not achieving complete response after induction chemotherapy: The GEL/TAMO experience. Ann Oncol 2004;15:1504-9.
Murthy V, Thomas K, Foo K, Cunningham D, Johnson B, Norman A. et al. Efficacy of palliative low-dose involved-field radiation therapy in advanced lymphoma: A phase II study. Clin Lymphoma Myeloma 2008;8:241-5.
Morschhauser F, Illidge T, Huglo D, Martinelli G, Paganelli G, Zinzani PL, et al. Efficacy and safety of Yttrium-90 ibritumomab tiuxetin in patients with relapsed and refractory diffuse large B-cell lymphoma not appropriate for autologous stem-cell transplantation. Blood 2007;110:54-8.
Coiffier B, Haioun C, Ketterer N, Engert A, Tilly H, Ma D, et al. Rituximab (Anti-CD20 Monoclonal Antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: A multicenter phase II study. Blood 1998;92:1927-32.
Guglielmi C, Gomez F, Philip T, Hagenbeek A, Martelli M, Sebban C, et al. Time to relapse has prognostic value in patients with aggressive lymphoma enrolled onto the Parma trial. J Clin Oncol 1998;16:3264-9.
Moskowitz CH, Zelenetz AD, Kewalramani T, Hamlin P, Lessac-Chenen S, Houldsworth J, et al. Cell of origin, germinal center versus non germinal center, determined by immunohistochemistry on tissue microarray, does not correlate with outcome in patients with relapsed and refractory DLBCL. Blood 2005;106:3383-5.
Moskowitz CH. Pretreatment prognostic factors and outcome in patients with relapsed or primary-refractory diffuse large B-cell lymphoma treated with second-line chemotherapy and autologous stem cell transplantation. Ann Oncol 2006;17(Suppl 4):iv37-9.
Vose JM, Bierman PJ, Anderson JR, Kessinger A, Pierson J, Nelson J, et al. Progressive disease after high-dose therapy and autologous transplantation for lymphoid malignancy: Clinical course and patient follow-up. Blood 1992;80:2142-8.
Pircher A, Gassner EM, Steurer M, Wolf D. Durable complete remission in a patient with recurrent DLBCL receiving rituximab monotherapy after high-dose chemotherapy and autologous stem cell transplantation. BMJ Case Rep 2012;2012.
Rezvani AR, Norasetthada L, Gooley T, Sorror M, Bouvier ME, Sahebi F, et al. Non-myeloablative allogeneic haematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: A multicentre experience. Br J Haematol 2008;143:395-403.
Anon. The international non-Hodgkin′s lymphoma prognostic factors project. A predictive model for aggressive non-Hodgkin′s lymphoma. N Engl J Med 1993;329:987-94.
Boehme V, Schmitz N, Zeynalova S, Loeffler M, Pfreundschuh M. CNS events in elderly patients with aggressive lymphoma treated with modern chemotherapy (CHOP-14) with or without rituximab: An analysis of patients treated in the RICOVER-60 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Blood 2009;113:3896-902.
Engelhard M, Brittinger G, Huhn D, Gerhartz HH, Meusers P, Siegert W, et al. Subclassification of diffuse large B-cell lymphomas according to the Kiel classification: Distinction of centroblastic and immunoblastic lymphomas is a significant prognostic risk factor. Blood 1997;89:2291-7.
Savage KJ, Johnson NA, Ben-Neriah S, Connors JM, Sehn LH, Farinha P, et al. MYC gene rearrangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients treated with R-CHOP chemotherapy. Blood 2009;114:3533-7.
Lenz G, Wright G, Dave SS, Xiao W, Powell J, Zhao H, et al. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med 2008;359:2313-23.
Yang DH, Ahn JS, Byun BH, Min JJ, Kweon SS, Chae YS, et al. Interim PET/CT-based prognostic model for the treatment of diffuse large B cell lymphoma in the post-rituximab era. Ann Hematol 2012 in press.
Porrata LF, Ristow K, Habermann TM, Ozsan N, Dogan A, Macon W, et al. Absolute monocyte/lymphocyte count prognostic score is independent of immunohistochemically determined cell of origin in predicting survival in diffuse large B-cell lymphoma. Leuk Lymphoma 2012;53:2159-65.
Haioun C, Mounier N, Emile JF, Bologna S, Coiffier B, Gisselbrecht C, et al. Rituximab compared to observation after high-dose consolidative first-line chemotherapy (HDC) with autologous stem cell transplantation in poor-risk diffuse large B-cell lymphoma: Updated results of the LNH98-B3 GELA study. J Clin Oncol 2007;25:Abstract 8012.
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[1] Cancer Facts and Figures 2012. American Cancer Society. Available from: http://www.cancer.org/. [Last accessed in 2013 Jan].

[2] de Leval L, Hasserjian RP. Diffuse Large B-Cell Lymphomas and Burkitt Lymphoma. Hematol Oncol Clin North Am 2009;23:791-827.

[3] Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: Evolving concepts and practical applications. Blood 2011;117:5019-32.

[4] Lenz G, Wright G, Dave SS, Xiao W, Powell J, Zhao H, et al. Stromal gene signatures in large B cell lymphomas. N Engl J Med 2008;359:2313-23.

[5] Lenz G, Staudt LM. Aggressive lymphomas. N Engl J Med 2010;362:1417-29.

[6] Garvin AJ, Simon RM, Osborne CK, Merrill J, Young RC, Berard CW. An autopsy study of histologic progression in non Hodgkin′s lymphomas: 192 cases from the National Cancer Institute. Cancer 1983;52:393-8.

[7] Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-b-cell lymphoma. N Engl J Med 2002;346:235-42.

[8] Perry AR, Goldstone AH. High-dose therapy for diffuse large-cell lymphoma in ﬁrst remission. Ann Oncol 1998;9(Suppl 1):S9-14.

[9] Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, et al. Comparison of a Standard Regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin′s Lymphoma N Engl J Med 1993;328:1002-6.

[10] Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, et al. Report of an international workshop to standardize response criteria for non-Hodgkin lymphomas. J Clin Oncol 1999;17:1244-53.

[11] Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: A randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol 2006;7:379-91.

[12] Hamlin PA, Zelenetz AD, Kewalramani T, Qin J, Satagopan JM, Verbel D, et al. Age-adjusted International Prognostic Index predicts autologous stem cell transplantation outcome for patients with relapsed or primary refractory diffuse large B-cell lymphoma. Blood 2003;102:1989-96.

[13] Weeks JC, Yeap BY, Canellos GP, Shipp MA. Value of follow-up procedures in patients with large-cell lymphoma who achieve a complete remission. J Clin Oncol 1991;9:1196-203.

[14] Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy sensitive non-Hodgkin lymphoma. N Engl J Med 1995;333:1540-5.

[15] Moskowitz CH, Bertino JR, Glassman JR, Hedrick EE, Hunte S, Coady-Lions N, et al. Ifosfamide, carboplatin and etoposide: A highly effective cyto-reduction and peripheral blood progenitor cell mobilization regimen for transplant-eligible patients with non-Hodgkins lymphoma. J Clin Oncol 1999;17:3776-85.

[16] Girouard C, Dufresne J, Imrie K, Stewart AK, Brandwein J, Prince HM, et al. Salvage chemotherapy with mini-BEAM for relapsed or refractory non-Hodgkins lymphoma prior to autologous bone marrow transplantation. Ann Oncol 1997;7:675-80.

[17] Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, et al. ESHAP - an effective chemotherapy regimen in refractory and relapsing lymphoma: A 4-year follow-up study. J Clin Oncol 1994;12:1169-76.

[18] Cabanillas F, Hagemeister FB, McLaughlin P, Velasquez WS, Riggs S, Fuller L, et al. Results of MIME salvage regimen for recurrent or refractory lymphoma. J Clin Oncol 1987;5:407-12.

[19] Gutierrez M, Chabner BA, Pearson D, Steinberg SM, Jaffe ES, Cheson BD, et al. Role of a Doxorubicin containing regimen in relapsed and resistant lymphomas: An 8-year follow-up study of EPOCH. J Clin Oncol 2000;18:3633-42.

[20] Coiffier B, Haioun C, Ketterer N, Engert A, Tilly H, Ma D, et al. Rituximab for the treatment of patients with relapsing or refractory aggressive lymphoma: A multicenter phase II study. Blood 1998;92:1927-32.

[21] Martín A, Conde E, Arnan M, Canales MA, Deben G, Sancho JM, et al. R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: The influence of prior exposure to rituximab on outcome. A GEL/TAMO study. Haematologica 2008;93:1829-36.

[22] Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, et al. Salvage regimens with autologous transplantation for relapsed large B-Cell lymphoma in the Rituximab Era. J Clin Oncol 2010;28:4184-90.

[23] Vellenga E, van Putten WL, van′t, Veer MB, Zijlstra JM, Fibbe WE, van Oers MH, et al. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+NHL: A prospective randomized HOVON trial. Blood 2008;111:537-43.

[24] Kewalramani T, Zelenetz AD, Nimer SD, Portlock C, Straus D, Noy A, 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;103:3684-8.

[25] Hicks L, Buckstein R, Mangel J, Piliotis E, Imrie K, Cheung MC, et al. Rituximab increases response to ESHAP in relapsed, refractory, and transformed aggressive B-cell lymphoma. Blood 2006;108:Abstract 3067.

[26] Zelenetz AD, Hamlin P, Kewalramani T, Yahalom J, Nimer S, Moskowitz CH. Ifosfamide, carboplatin, etoposide (ICE) based second line chemotherapy for the management of relapsed and refractory aggressive non Hodgkin′s lymphoma. Ann Oncol 2003;14(Suppl 1):i5-10.

[27] El Gnaoui T, Dupuis J, Belhadj K, Jais JP, Rahmouni A, Copie-Bergman C, et al. Rituximab, gemcitabine and oxaliplatin: An effective salvage regimen for patients with relapsed or refractory B cell Lymphoma not candidates for high dose therapy. Ann Oncol 2007;18:1363-8.

[28] Lignon J, Sibon D, Madelaine I, Brice P, Franchi P, Briere J, et al. Rituximab, dexamethasone, cytarabine, and oxaliplatin (R-DHAX) is an effective and safe salvage regimen in relapsed/refractory B-cell non-Hodgkin lymphoma. Clin Lymph Myeloma Leuk 2010;10:262-9.

[29] Corazzelli G, Russo F, Capobianco G, Marcacci G, Della Cioppa P, Pinto A. Gemcitabine, ifosfamide, oxaliplatin and Rituximab (R-GIFOX), a new effective cytoreductive/mobilizing salvage regimen for relapsed and refractory aggressive non-Hodgkin′s lymphoma: Results of a pilot study. Ann Oncol 2006;17(Suppl 4):iv18-24.

[30] Tarella C, Zanni M, Magni M, Benedetti F, Barbui T, Boccadoro M, et al. Benefit of rituximab addition to high-dose programs with autograft for B-cell lymphoma: A multicenter GITIL survey on 957 patients. Blood 2006;108:Abstract 207.

[31] Thieblemont C, Briere J, Mounier N, Voelker HU, Cuccuini W, Hirchaud E, et al. The Germinal center/activated B-cell subclassiﬁcation has a prognostic impact for response to salvage therapy in relapsed/refractory diffuse large B-cell lymphoma: A bio-CORAL study. J Clin Oncol 2011;29:4079-87.

[32] Rodriguez J, Caballero MD, Gutierrez A, Solano C, Arranz R, Lahuerta JJ, et al. Autologous stem-cell transplantation in diffuse large B-cell non-Hodgkin′s lymphoma not achieving complete response after induction chemotherapy: The GEL/TAMO experience. Ann Oncol 2004;15:1504-9.

[33] Murthy V, Thomas K, Foo K, Cunningham D, Johnson B, Norman A. et al. Efficacy of palliative low-dose involved-field radiation therapy in advanced lymphoma: A phase II study. Clin Lymphoma Myeloma 2008;8:241-5.

[34] Morschhauser F, Illidge T, Huglo D, Martinelli G, Paganelli G, Zinzani PL, et al. Efficacy and safety of Yttrium-90 ibritumomab tiuxetin in patients with relapsed and refractory diffuse large B-cell lymphoma not appropriate for autologous stem-cell transplantation. Blood 2007;110:54-8.

[35] Coiffier B, Haioun C, Ketterer N, Engert A, Tilly H, Ma D, et al. Rituximab (Anti-CD20 Monoclonal Antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: A multicenter phase II study. Blood 1998;92:1927-32.

[36] Guglielmi C, Gomez F, Philip T, Hagenbeek A, Martelli M, Sebban C, et al. Time to relapse has prognostic value in patients with aggressive lymphoma enrolled onto the Parma trial. J Clin Oncol 1998;16:3264-9.

[37] Moskowitz CH, Zelenetz AD, Kewalramani T, Hamlin P, Lessac-Chenen S, Houldsworth J, et al. Cell of origin, germinal center versus non germinal center, determined by immunohistochemistry on tissue microarray, does not correlate with outcome in patients with relapsed and refractory DLBCL. Blood 2005;106:3383-5.

[38] Moskowitz CH. Pretreatment prognostic factors and outcome in patients with relapsed or primary-refractory diffuse large B-cell lymphoma treated with second-line chemotherapy and autologous stem cell transplantation. Ann Oncol 2006;17(Suppl 4):iv37-9.

[39] Vose JM, Bierman PJ, Anderson JR, Kessinger A, Pierson J, Nelson J, et al. Progressive disease after high-dose therapy and autologous transplantation for lymphoid malignancy: Clinical course and patient follow-up. Blood 1992;80:2142-8.

[40] Pircher A, Gassner EM, Steurer M, Wolf D. Durable complete remission in a patient with recurrent DLBCL receiving rituximab monotherapy after high-dose chemotherapy and autologous stem cell transplantation. BMJ Case Rep 2012;2012.

[41] Rezvani AR, Norasetthada L, Gooley T, Sorror M, Bouvier ME, Sahebi F, et al. Non-myeloablative allogeneic haematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: A multicentre experience. Br J Haematol 2008;143:395-403.

[42] Anon. The international non-Hodgkin′s lymphoma prognostic factors project. A predictive model for aggressive non-Hodgkin′s lymphoma. N Engl J Med 1993;329:987-94.

[43] Boehme V, Schmitz N, Zeynalova S, Loeffler M, Pfreundschuh M. CNS events in elderly patients with aggressive lymphoma treated with modern chemotherapy (CHOP-14) with or without rituximab: An analysis of patients treated in the RICOVER-60 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Blood 2009;113:3896-902.

[44] Engelhard M, Brittinger G, Huhn D, Gerhartz HH, Meusers P, Siegert W, et al. Subclassification of diffuse large B-cell lymphomas according to the Kiel classification: Distinction of centroblastic and immunoblastic lymphomas is a significant prognostic risk factor. Blood 1997;89:2291-7.

[45] Savage KJ, Johnson NA, Ben-Neriah S, Connors JM, Sehn LH, Farinha P, et al. MYC gene rearrangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients treated with R-CHOP chemotherapy. Blood 2009;114:3533-7.

[46] Lenz G, Wright G, Dave SS, Xiao W, Powell J, Zhao H, et al. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med 2008;359:2313-23.

[47] Yang DH, Ahn JS, Byun BH, Min JJ, Kweon SS, Chae YS, et al. Interim PET/CT-based prognostic model for the treatment of diffuse large B cell lymphoma in the post-rituximab era. Ann Hematol 2012 in press.

[48] Porrata LF, Ristow K, Habermann TM, Ozsan N, Dogan A, Macon W, et al. Absolute monocyte/lymphocyte count prognostic score is independent of immunohistochemically determined cell of origin in predicting survival in diffuse large B-cell lymphoma. Leuk Lymphoma 2012;53:2159-65.

[49] Haioun C, Mounier N, Emile JF, Bologna S, Coiffier B, Gisselbrecht C, et al. Rituximab compared to observation after high-dose consolidative first-line chemotherapy (HDC) with autologous stem cell transplantation in poor-risk diffuse large B-cell lymphoma: Updated results of the LNH98-B3 GELA study. J Clin Oncol 2007;25:Abstract 8012.

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Management of relapsed-refractory diffuse large B cell lymphoma

Abstract

Abstract

Keywords

Acknowledgment

References

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