Abstract
High-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) is considered standard in the treatment of patients with relapsed or refractory aggressive peripheral T cell lymphoma (PTCL). However, the optimal salvage regimen before ASCT has not yet been established. We retrospectively analyzed 31 patients with relapsed or refractory aggressive PTCL after anthracycline-based first-line chemotherapy who received either DexaBEAM (dexamethasone, carmustine, etoposide, cytarabine, and melphalan; n = 16) or ICE (ifosfamide, carboplatin, and etoposide; n = 15) regimen as first salvage chemotherapy followed by HDT/ASCT. The overall response rate (OR) was significantly higher for patients treated with DexaBEAM (69 %; 95 % confidence interval 46.0–91.5 %) as compared to the ICE group (20 %; 95 % confidence interval −0.2–40.2 %; P = 0.01), with higher complete response (CR; 38 %; 95 % confidence interval 13.8–61.2 %; vs. 7 %; 95 % confidence interval −6.0–19.6 %) as well as partial response (PR; 31 vs. 13 %) rate. Changing regimen due to failure of first salvage therapy, 12 patients initially receiving ICE still achieved an OR of 58 % (33 % CR, 25 % PR) with DexaBEAM as second salvage therapy, whereas in three patients receiving ICE after DexaBEAM failure, only one achieved an OR (1 PR). Median progression-free survival was significantly higher in the DexaBEAM group (6.4 vs. 2 months; P = 0.01). Major adverse event in both groups was myelosuppression with higher but tolerable treatment-related toxicity for patients in the DexaBEAM group. For all patients proceeding to HDT/ASCT, a 3-year overall survival was 50 %. Together, considering the limitations of the retrospective design of the evaluation and the small sample size, our data suggest that DexaBEAM salvage chemotherapy is superior to ICE for patients with relapsed or refractory aggressive PTCL for remission induction prior to autologous transplantation, with higher but manageable treatment-related toxicity.
Similar content being viewed by others
References
Foss FM, Zinzani PL, Vose JM, Gascyone RD, Rosen ST, Tobinai K (2011) Peripheral T-cell lymphoma. Blood 117:6756–6767
Shankland KR, Armitage JO, Hancock BW (2012) Non-Hodgkin lymphoma. Lancet 380:848–857
Vose J, Armitage J, Weisenburger D (2008) International T-Cell Lymphoma Project. International peripheral T-Cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol 26:4124–4130
Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346:235–242
Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ (2006) Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol 24:3121–3127
Pfreundschuh M, Ho AD, Cavallin-Stahl E, Wolf M, Pettengell R, Vasova I, Belch A, Walewski J, Zinzani PL, Mingrone W, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Corrado C, Scheliga A, Loeffler M, Kuhnt E, MabThera International trial (MInT) Group (2008) Prognostic significance of maximum tumour (bulk) diameter in young patients with good-prognosis diffuse large-B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: an exploratory analysis of the MabThera International Trial Group (MInT) study. Lancet Oncol 9:435–444
Armitage JO (2012) The aggressive peripheral T-cell lymphomas: 2012 update on diagnosis, risk stratification, and management. Am J Hematol 87:511–519
Federico M, Rudiger T, Bellei M, Nathwani BN, Luminari S, Coiffier B, Harris NL, Jaffe ES, Pileri SA, Savage KJ, Weisenburger DD, Armitage JO, Mounier N, Vose JM (2013) Clinicopathologic characteristics of angioimmunoblastic T-cell lymphoma (AITL): analysis of 243 cases from the International Peripheral T-cell Lymphoma Project. J Clin Oncol 31:240–246
Ferreri AJ, Govi S, Pileri SA, Savage KJ (2012) Anaplastic large cell lymphoma, ALK positive. Crit Rev Oncol Hematol 83:293–302
Savage KJ, Harris NL, Vose JM, Ullrich F, Jaffe ES, Connors JM, Rimsza L, Pileri SA, Chhanabhai M, Gascoyne RD, Armitage JO, Weisenburger DD, International Peripheral T-Cell Lymphoma Project (2008) ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International T-Cell Lymphoma Project. Blood 111:5496–5504
Greer JP (2006) Therapy of peripheral T/NK neoplasm. Hematol Am Soc Hematol Educ Program 2006:331–337
Philip T, Guglielmini C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau et al (1995) Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma. N Engl J Med 333:1540–1545
Gutiérrez A, Caballero MD, Pérez-Manga G, Rodriguez J (2008) Hematopoietic SCT for peripheral T-cell lymphoma. Bone Marrow Transplant 42:773–781
Kyriakou C, Canals C, Goldstone A, Caballero D, Metzner B, Kobbe G, Kolb HJ, Kienast J, Reimer P, Finke J, Oberg G, Hunter A, Theorin N, Sureda A, Schmitz N, Outcome-Lymphoma Working Party of the European Group for Blood and Marrow Transplantation (2008) High-dose therapy and autologous stem-cell transplantation in angioimmunoblastic lymphoma: complete remission at transplantation is the major determinant of Outcome-Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 26:218–224
Hosing C, Champlin RE (2011) Stem-cell transplantation in T-cell non-Hodgkin lymphomas. Ann Oncol 22:1471–1477
Schetelig J, Fetscher S, Reichle A, Berdel WE, Beguin Y, Brunet S, Caballero D, Majolino I, Hagberg H, Johnsen HE, Kimby E, Montserrat E, Stewart D, Copplestone A, Rösler W, Pavel J, Kingreen D, Siegert W (2003) Long-term disease-free survival in patients with angioimmunoblastic T-cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation. Haematologica 88:1272–1278
Kim MK, Kim S, Lee SS, Sym SJ, Lee DH, Jang S, Park CJ, Chi HS, Huh J, Suh C (2007) High-dose chemotherapy and autologous stem cell transplantation for peripheral T-cell lymphoma: complete response at transplant predicts survival. Ann Haematol 86:435–442
Rodríguez J, Caballero MD, Gutiérrez A, Marin J, Lahuerta JJ, Sureda A, Carreras E, Leon A, Arranz R, Fernandez de Sevilla A, Zuazu J, Garcia-Larana J, Rifon J, Varela R, Gandarillas M, SanMiguel J, Conde (2003) High dose chemotherapy and autologous stem cell transplantation in peripheral T-cell lymphoma: the GEL-TAMO experience. Ann Oncol 14:1768–1775
Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Briere J, Moskowitz CH, Schmitz N (2010) Salvage regimens with autologous transplantation for relapsed large cell lymphoma in the rituximab era. J Clin Oncol 28:4184–4190
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (2008) WHO classification of tumours of haematopoietic and lymphoid tissues. IARC, Lyon
Blay J, Gomez F, Sebban C, Bachelot T, Biron P, Guglielmi C, Hagenbeek A, Somers R, Chauvin F, Philip T (1998) The International Prognostic Index correlates to survival in patients with aggressive lymphoma in relapse: analysis of the PARMA trial. Parma Group. Blood 92:3562–3568
Hamlin PA, Zelenetz AD, Kewalramani T, Qin J, Satagopan JM, Verbel D, Noy A, Portlock CS, Straus DJ, Yahalom J, Nimer SD, Moskowitz CH (2003) Age-adjusted International Prognostic Index predicts autologous stem cell transplantation outcome for patients with relapsed or primary refractory diffuse large B-cell lymphoma. Blood 102:1989–1996
Atta J, Chouw KU, Weidmann E, Mitrou PS, Hoelzer D (2007) Martin H (2007) DexaBEAM as salvage therapy in patients with primary refractory aggressive non-Hodgkin lymphoma. Leuk Lymphoma 48:349–356
Zelenetz AD, Hamlin P, Kewalramani T, Yahalom J, Nimer S, Moskowitz CH (2003) Ifosfamide, carboplatin, etoposide (ICE)-based second-line chemotherapy for the management of relapsed and refractory aggressive non-Hodgkin’s lymphoma. Ann Oncol Suppl 1:i5–i10
Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-Lopez A, Hagenbeek A, Cabanillas F, Klippenstein D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP (1999) Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. NCI Sponsored International Working Group. J Clin Oncol 17:1244–1253
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 (2007) Revised response criteria for malignant lymphoma. J Clin Oncol 25:579–586
Chen AI, McMillan A, Negrin RS, Horning SJ, Laport GG (2008) Long-term results of autologous hematopoietic cell transplantation for peripheral T cell lymphoma: the Stanford experience. Biol Blood Marrow Transplant 14:741–747
D’Amore F, Relander T, Lauritzsen GF, Jantunen E, Hagberg H, Anderson H, Holte H, Österborg A, Merup M, Brown P, Kuittinen O, Erlanson M, Ostenstad B, Fagerli UM, Gadeberg OV, Sundström C, Delabie J, Ralfkiaer E, Vornanen M, Toldbod HE (2012) Up-front autologous stem cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol 30:3093–3099
Josting A, Sienawski M, Glossmann JP, Staak O, Nogova L, Peters N, Mapara M, Dörken B, Ko Y, Metzner B, Kisro J, Diehl V, Engert A (2005) High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-Hodgkin’s lymphoma: results of a multicenter phase II study. Ann Oncol 16:1359–1365
Kim KH, Joo YD, Sohn CH, Shin HJ, Chung JS, Cho GJ, Shin SH, Kim YS, Lee WS (2009) Gemcitabine, etoposide, cisplatin, and dexamethasone in patients with refractory or relapsed non-Hodgkin’s lymphoma. Korean J Intern Med 24:37–42
Park BB, Kim WS, Lee J, Park KW, Kang JH, Lee SH, Park JO, Kim K, Jung CW, Park YS, Im YH, Kang WK, Ko YH, Lee MH, Park K (2005) IMVP-16/Pd followed by high-dose chemotherapy and autologous stem cell transplantation as a salvage therapy for refractory or relapsed peripheral T-cell lymphomas. Leuk Lymphoma 46:1743–1748
Pro B, Advani RH, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, Matous J, Ramchandren R, Fanale M, Connors JM, Yang Y, Sievers EL, Kennedy DA, Shustov A (2012) Brentuximab vedotin (SGN-35) in patients with relapsed of refractory systemic anaplastic large cell lymphoma: results of a phase II study. J Clin Oncol 30:2190–2196
Coiffier B, Pro B, Prince HM, Foss F, Sokol L, Greenwood M, Caballero D, Borchmann P, Morschhauser F, Wilhelm M, Pinter-Brown L, Padmanabhan S, Shustov A, Nichols J, Carroll S, Balser J, Balser B, Horwitz S (2012) Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J Clin Oncol 30:631–636
Enblad G, Hagberg H, Erlanson M, Lundin J, MacDonald AP, Repp R, Schetelig J, Seipelt G, Osterborg A (2004) A pilot study of alemtuzumab (anti-CD52 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas. Blood 103:2920–2924
Gallamini A, Zaja F, Patti C, Billio A, Specchia MR, Tucci A, Levis A, Manna A, Secondo V, Rigacci L, Pinto A, Iannitto E, Zoli V, Torchio P, Pileri S, Tarella C (2007) Alemtuzumab (Campath-1H) and CHOP chemotherapy as first-line treatment of peripheral T-cell lymphoma: results of a GITIL (Gruppo Italiano Terapie Innovative nei Linfomi) prospective multicenter trial. Blood 110:2316–2323
Kim SJ, Kim K, Kim BS, Suh C, Huh J, Ko YH, Kim WS (2009) Alemtuzumab and DHAP (A-DHAP) is effective for relapsed peripheral T-cell lymphoma, unspecified: interim results of a phase II prospective study. Ann Oncol 20:390–392
Prichard M, Harris T, Williams ME, Densmore JJ (2009) Treatment strategies for relapsed and refractory aggressive non-Hodgkin’s lymphoma. Expert Opin Pharmacother 10:983–995
Conflict of Interest
The authors have declared no potential conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
J.H.M. and M.K. contributed equally to the manuscript and share the first authorship. N.H.T. and W.E.B. contributed equally to the manuscript and share senior authorship.
Rights and permissions
About this article
Cite this article
Mikesch, JH., Kuhlmann, M., Demant, A. et al. DexaBEAM versus ICE salvage regimen prior to autologous transplantation for relapsed or refractory aggressive peripheral T cell lymphoma: a retrospective evaluation of parallel patient cohorts of one center. Ann Hematol 92, 1041–1048 (2013). https://doi.org/10.1007/s00277-013-1738-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-013-1738-9