Dose-dense and high-dose chemotherapy plus rituximab with autologous stem cell transplantation for primary treatment of diffuse large B-cell lymphoma with a poor prognosis: A phase II multicenter study

Umberto Vitolo, Annalisa Chiappella, Emanuele Angelucci, Giuseppe Rossi, Anna Marina Liberati, Maria Giuseppina Cabras, Barbara Botto, Giovannino Ciccone, Gianluca Gaidano, Lorenzo Falchi, Roberto Freilone, Domenico Novero, Lorella Orsucci, Vincenzo Pavone, Enrico Pogliani, Delia Rota-Scalabrini, Flavia Salvi, Anna Tonso, Alessandra Tucci, Alessandro Levis

Research output: Contribution to journalArticle

Abstract

Background: We investigated the addition of rituximab to dose-dense and high-dose chemotherapy with autologous stem cell transplantation in patients with untreated poor-prognosis diffuse large B-cell lymphoma. Design and Methods: Ninety-four young patients (age, 18-60) with stage III-IV diffuse large B-cell lymphoma at intermediate/high or high risk according to the age-adjusted International Prognostic Index were enrolled into a phase II trial. The treatment was as follows: four courses of bi-weekly rituximab-cyclophosphamide- epirubicin-vincristine-prednisone (R-MegaCEOP14), two courses of rituximab-mitoxantrone-cytarabine-dexamethasone (R-MAD) and carmustineetoposide- cytarabine-melphalan (BEAM) with autologous stem cell transplantation. Results: The complete response and toxic death rates were 82% and 5%, respectively. Failure-free survival and overall survival rates at 4 years were 73% and 80%, respectively. The outcomes of these patients were retrospectively compared to those of 41 patients with similar characteristics enrolled into a previous phase II trial of high-dose chemotherapy without rituximab. This historical group was treated with eight weekly infusions of methotrexatedoxorubicin- cyclophosphamide-vincristine-prednisone-bleomycin (MACOP-B), two courses of MAD and BEAM with autologous stem cell transplantation. The 4-year failure-sfree survival rates for the rituximab and historical groups were 73% versus 44%, respectively (p=0.001); the 4-year overall survival rates were 80% and 54%, respectively (p=0.002). A Cox's multivariable model was applied to adjust the effect of treatment for unbalanced or important prognostic factors: failure and death risks were significantly reduced in the rituximab group compared to the historical group, with an adjusted hazard ratio of 0.44 (p=0.01) for failure-free survival and 0.46 (p=0.02) for overall survival. Conclusions: These results suggest that the addition of rituximab to high-dose chemotherapy is effective and safe in diffuse large B-cell lymphoma with a poor-prognosis and such regimens need to be compared to dose-dense chemoimmunotherapy without autologous stem cell transplantation in randomized trials. (ClinicalTrials.gov Identifier: NCT00556127).

Original languageEnglish
Pages (from-to)1250-1258
Number of pages9
JournalHaematologica
Volume94
Issue number9
DOIs
Publication statusPublished - Sep 2009

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Lymphoma, Large B-Cell, Diffuse
Stem Cell Transplantation
Multicenter Studies
Drug Therapy
Survival Rate
Cytarabine
Vincristine
Prednisone
Cyclophosphamide
Therapeutics
Survival
Mitoxantrone
Epirubicin
Melphalan
Poisons
Bleomycin
Rituximab
Proportional Hazards Models
Dexamethasone
Mortality

Keywords

  • Autologous stem cell transplantation
  • Diffuse large B-cell lymphoma
  • Dose-dense chemotherapy
  • High-dose chemotherapy
  • Poor prognosis
  • Rituximab

ASJC Scopus subject areas

  • Hematology

Cite this

Dose-dense and high-dose chemotherapy plus rituximab with autologous stem cell transplantation for primary treatment of diffuse large B-cell lymphoma with a poor prognosis : A phase II multicenter study. / Vitolo, Umberto; Chiappella, Annalisa; Angelucci, Emanuele; Rossi, Giuseppe; Liberati, Anna Marina; Cabras, Maria Giuseppina; Botto, Barbara; Ciccone, Giovannino; Gaidano, Gianluca; Falchi, Lorenzo; Freilone, Roberto; Novero, Domenico; Orsucci, Lorella; Pavone, Vincenzo; Pogliani, Enrico; Rota-Scalabrini, Delia; Salvi, Flavia; Tonso, Anna; Tucci, Alessandra; Levis, Alessandro.

In: Haematologica, Vol. 94, No. 9, 09.2009, p. 1250-1258.

Research output: Contribution to journalArticle

Vitolo, U, Chiappella, A, Angelucci, E, Rossi, G, Liberati, AM, Cabras, MG, Botto, B, Ciccone, G, Gaidano, G, Falchi, L, Freilone, R, Novero, D, Orsucci, L, Pavone, V, Pogliani, E, Rota-Scalabrini, D, Salvi, F, Tonso, A, Tucci, A & Levis, A 2009, 'Dose-dense and high-dose chemotherapy plus rituximab with autologous stem cell transplantation for primary treatment of diffuse large B-cell lymphoma with a poor prognosis: A phase II multicenter study', Haematologica, vol. 94, no. 9, pp. 1250-1258. https://doi.org/10.3324/haematol.2009.007005
Vitolo, Umberto ; Chiappella, Annalisa ; Angelucci, Emanuele ; Rossi, Giuseppe ; Liberati, Anna Marina ; Cabras, Maria Giuseppina ; Botto, Barbara ; Ciccone, Giovannino ; Gaidano, Gianluca ; Falchi, Lorenzo ; Freilone, Roberto ; Novero, Domenico ; Orsucci, Lorella ; Pavone, Vincenzo ; Pogliani, Enrico ; Rota-Scalabrini, Delia ; Salvi, Flavia ; Tonso, Anna ; Tucci, Alessandra ; Levis, Alessandro. / Dose-dense and high-dose chemotherapy plus rituximab with autologous stem cell transplantation for primary treatment of diffuse large B-cell lymphoma with a poor prognosis : A phase II multicenter study. In: Haematologica. 2009 ; Vol. 94, No. 9. pp. 1250-1258.
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abstract = "Background: We investigated the addition of rituximab to dose-dense and high-dose chemotherapy with autologous stem cell transplantation in patients with untreated poor-prognosis diffuse large B-cell lymphoma. Design and Methods: Ninety-four young patients (age, 18-60) with stage III-IV diffuse large B-cell lymphoma at intermediate/high or high risk according to the age-adjusted International Prognostic Index were enrolled into a phase II trial. The treatment was as follows: four courses of bi-weekly rituximab-cyclophosphamide- epirubicin-vincristine-prednisone (R-MegaCEOP14), two courses of rituximab-mitoxantrone-cytarabine-dexamethasone (R-MAD) and carmustineetoposide- cytarabine-melphalan (BEAM) with autologous stem cell transplantation. Results: The complete response and toxic death rates were 82{\%} and 5{\%}, respectively. Failure-free survival and overall survival rates at 4 years were 73{\%} and 80{\%}, respectively. The outcomes of these patients were retrospectively compared to those of 41 patients with similar characteristics enrolled into a previous phase II trial of high-dose chemotherapy without rituximab. This historical group was treated with eight weekly infusions of methotrexatedoxorubicin- cyclophosphamide-vincristine-prednisone-bleomycin (MACOP-B), two courses of MAD and BEAM with autologous stem cell transplantation. The 4-year failure-sfree survival rates for the rituximab and historical groups were 73{\%} versus 44{\%}, respectively (p=0.001); the 4-year overall survival rates were 80{\%} and 54{\%}, respectively (p=0.002). A Cox's multivariable model was applied to adjust the effect of treatment for unbalanced or important prognostic factors: failure and death risks were significantly reduced in the rituximab group compared to the historical group, with an adjusted hazard ratio of 0.44 (p=0.01) for failure-free survival and 0.46 (p=0.02) for overall survival. Conclusions: These results suggest that the addition of rituximab to high-dose chemotherapy is effective and safe in diffuse large B-cell lymphoma with a poor-prognosis and such regimens need to be compared to dose-dense chemoimmunotherapy without autologous stem cell transplantation in randomized trials. (ClinicalTrials.gov Identifier: NCT00556127).",
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TY - JOUR

T1 - Dose-dense and high-dose chemotherapy plus rituximab with autologous stem cell transplantation for primary treatment of diffuse large B-cell lymphoma with a poor prognosis

T2 - A phase II multicenter study

AU - Vitolo, Umberto

AU - Chiappella, Annalisa

AU - Angelucci, Emanuele

AU - Rossi, Giuseppe

AU - Liberati, Anna Marina

AU - Cabras, Maria Giuseppina

AU - Botto, Barbara

AU - Ciccone, Giovannino

AU - Gaidano, Gianluca

AU - Falchi, Lorenzo

AU - Freilone, Roberto

AU - Novero, Domenico

AU - Orsucci, Lorella

AU - Pavone, Vincenzo

AU - Pogliani, Enrico

AU - Rota-Scalabrini, Delia

AU - Salvi, Flavia

AU - Tonso, Anna

AU - Tucci, Alessandra

AU - Levis, Alessandro

PY - 2009/9

Y1 - 2009/9

N2 - Background: We investigated the addition of rituximab to dose-dense and high-dose chemotherapy with autologous stem cell transplantation in patients with untreated poor-prognosis diffuse large B-cell lymphoma. Design and Methods: Ninety-four young patients (age, 18-60) with stage III-IV diffuse large B-cell lymphoma at intermediate/high or high risk according to the age-adjusted International Prognostic Index were enrolled into a phase II trial. The treatment was as follows: four courses of bi-weekly rituximab-cyclophosphamide- epirubicin-vincristine-prednisone (R-MegaCEOP14), two courses of rituximab-mitoxantrone-cytarabine-dexamethasone (R-MAD) and carmustineetoposide- cytarabine-melphalan (BEAM) with autologous stem cell transplantation. Results: The complete response and toxic death rates were 82% and 5%, respectively. Failure-free survival and overall survival rates at 4 years were 73% and 80%, respectively. The outcomes of these patients were retrospectively compared to those of 41 patients with similar characteristics enrolled into a previous phase II trial of high-dose chemotherapy without rituximab. This historical group was treated with eight weekly infusions of methotrexatedoxorubicin- cyclophosphamide-vincristine-prednisone-bleomycin (MACOP-B), two courses of MAD and BEAM with autologous stem cell transplantation. The 4-year failure-sfree survival rates for the rituximab and historical groups were 73% versus 44%, respectively (p=0.001); the 4-year overall survival rates were 80% and 54%, respectively (p=0.002). A Cox's multivariable model was applied to adjust the effect of treatment for unbalanced or important prognostic factors: failure and death risks were significantly reduced in the rituximab group compared to the historical group, with an adjusted hazard ratio of 0.44 (p=0.01) for failure-free survival and 0.46 (p=0.02) for overall survival. Conclusions: These results suggest that the addition of rituximab to high-dose chemotherapy is effective and safe in diffuse large B-cell lymphoma with a poor-prognosis and such regimens need to be compared to dose-dense chemoimmunotherapy without autologous stem cell transplantation in randomized trials. (ClinicalTrials.gov Identifier: NCT00556127).

AB - Background: We investigated the addition of rituximab to dose-dense and high-dose chemotherapy with autologous stem cell transplantation in patients with untreated poor-prognosis diffuse large B-cell lymphoma. Design and Methods: Ninety-four young patients (age, 18-60) with stage III-IV diffuse large B-cell lymphoma at intermediate/high or high risk according to the age-adjusted International Prognostic Index were enrolled into a phase II trial. The treatment was as follows: four courses of bi-weekly rituximab-cyclophosphamide- epirubicin-vincristine-prednisone (R-MegaCEOP14), two courses of rituximab-mitoxantrone-cytarabine-dexamethasone (R-MAD) and carmustineetoposide- cytarabine-melphalan (BEAM) with autologous stem cell transplantation. Results: The complete response and toxic death rates were 82% and 5%, respectively. Failure-free survival and overall survival rates at 4 years were 73% and 80%, respectively. The outcomes of these patients were retrospectively compared to those of 41 patients with similar characteristics enrolled into a previous phase II trial of high-dose chemotherapy without rituximab. This historical group was treated with eight weekly infusions of methotrexatedoxorubicin- cyclophosphamide-vincristine-prednisone-bleomycin (MACOP-B), two courses of MAD and BEAM with autologous stem cell transplantation. The 4-year failure-sfree survival rates for the rituximab and historical groups were 73% versus 44%, respectively (p=0.001); the 4-year overall survival rates were 80% and 54%, respectively (p=0.002). A Cox's multivariable model was applied to adjust the effect of treatment for unbalanced or important prognostic factors: failure and death risks were significantly reduced in the rituximab group compared to the historical group, with an adjusted hazard ratio of 0.44 (p=0.01) for failure-free survival and 0.46 (p=0.02) for overall survival. Conclusions: These results suggest that the addition of rituximab to high-dose chemotherapy is effective and safe in diffuse large B-cell lymphoma with a poor-prognosis and such regimens need to be compared to dose-dense chemoimmunotherapy without autologous stem cell transplantation in randomized trials. (ClinicalTrials.gov Identifier: NCT00556127).

KW - Autologous stem cell transplantation

KW - Diffuse large B-cell lymphoma

KW - Dose-dense chemotherapy

KW - High-dose chemotherapy

KW - Poor prognosis

KW - Rituximab

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DO - 10.3324/haematol.2009.007005

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