High dose sequential chemotherapy with autologous transplantation versus dose-dense chemotherapy MegaCEOP as first line treatment in poor-prognosis diffuse large cell lymphoma: An "Intergruppo Italiano Linfomi" randomized trial

Umberto Vitolo, Anna Marina Liberati, Maria Giuseppina Cabras, Massimo Federico, Emanuele Angelucci, Luca Baldini, Carola Boccomini, Maura Brugiatelli, Roberta Calvi, Giovannino Ciccone, Angelo Genua, Giorgio Lambertenghi Deliliers, Alessandro Levis, Guido Parvis, Enzo Pavone, Ravia Salvi, Marco Sborgia, Eugenio Gallo

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Abstract

Background and Objectives. Poor prognosis diffuse large cell lymphoma (DLCL) responds poorly to standard chemotherapy. Randomized studies comparing high-dose chemotherapy with autologous stem-cell transplantation (ASCT) against standard chemotherapy have produced conflicting results. Dose-dense chemotherapy with granulocyte colony-stimulating factor (G-CSF) support seems to hold promise. The purpose of this multicenter, randomized trial was to compare failure-free and overall survival in patients with poor prognosis DLCL treated with high-dose sequential (HDS) chemotherapy followed by ASCT or an outpatient dose-dense chemotherapy regimen (MegaCEOP). Design and Methods. Between 1996 and 2001, 130 DLCL patients, aged ≤ 60 years, with intermediate-high or high-risk disease, according to the International Prognostic Index score, and/or bone marrow involvement were enrolled. Sixty were randomized to HDS chemotherapy plus high-dose mitoxantrone and melphalan with ASCT (arm A) and 66 to the MegaCEOP regimen (6-8 courses of an escalated dose of cyclophosphamide and epirubicin plus vincristine and prednisone with G-CSF every 2-weeks) (arm B); 4 patients were considered ineligible. Results. The complete remission rate was 59% in arm A and 70% in arm B (p=0.18). After a median follow-up of 78 months, the 6-year failure-free survival was 45% in arm A and 48% in arm B (hazard ratio=1.15, 95% confidence intervals =0.72-1.84, p=0.56). The 5-year overall survival was 49% in arm A and 63% in arm B (hazard ratio=1.67, 95% confidence interval=0.98-2.85, p=0.06). Two cases of secondary acute myeloid leukemia were observed after treatment in group A. Interpretations and Conclusions. HDS and ASCT as initial therapy for patients with poor-prognosis DLCL does not provide a benefit over that of outpatient dose-dense MegaCEOP chemotherapy.

Original languageEnglish
Pages (from-to)793-801
Number of pages9
JournalHaematologica
Volume90
Issue number6
Publication statusPublished - Jun 2005

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Lymphoma, Large B-Cell, Diffuse
Autologous Transplantation
Drug Therapy
Stem Cell Transplantation
Granulocyte Colony-Stimulating Factor
Therapeutics
Survival
Outpatients
Confidence Intervals
Mitoxantrone
Epirubicin
Melphalan
Vincristine
Granulocyte-Macrophage Colony-Stimulating Factor
Prednisone
Acute Myeloid Leukemia
Cyclophosphamide
Multicenter Studies
Bone Marrow

Keywords

  • Autologous transplantation
  • Dose-dense chemotherapy
  • Poor-prognosis DLCL

ASJC Scopus subject areas

  • Hematology

Cite this

High dose sequential chemotherapy with autologous transplantation versus dose-dense chemotherapy MegaCEOP as first line treatment in poor-prognosis diffuse large cell lymphoma : An "Intergruppo Italiano Linfomi" randomized trial. / Vitolo, Umberto; Liberati, Anna Marina; Cabras, Maria Giuseppina; Federico, Massimo; Angelucci, Emanuele; Baldini, Luca; Boccomini, Carola; Brugiatelli, Maura; Calvi, Roberta; Ciccone, Giovannino; Genua, Angelo; Deliliers, Giorgio Lambertenghi; Levis, Alessandro; Parvis, Guido; Pavone, Enzo; Salvi, Ravia; Sborgia, Marco; Gallo, Eugenio.

In: Haematologica, Vol. 90, No. 6, 06.2005, p. 793-801.

Research output: Contribution to journalArticle

Vitolo, U, Liberati, AM, Cabras, MG, Federico, M, Angelucci, E, Baldini, L, Boccomini, C, Brugiatelli, M, Calvi, R, Ciccone, G, Genua, A, Deliliers, GL, Levis, A, Parvis, G, Pavone, E, Salvi, R, Sborgia, M & Gallo, E 2005, 'High dose sequential chemotherapy with autologous transplantation versus dose-dense chemotherapy MegaCEOP as first line treatment in poor-prognosis diffuse large cell lymphoma: An "Intergruppo Italiano Linfomi" randomized trial', Haematologica, vol. 90, no. 6, pp. 793-801.
Vitolo, Umberto ; Liberati, Anna Marina ; Cabras, Maria Giuseppina ; Federico, Massimo ; Angelucci, Emanuele ; Baldini, Luca ; Boccomini, Carola ; Brugiatelli, Maura ; Calvi, Roberta ; Ciccone, Giovannino ; Genua, Angelo ; Deliliers, Giorgio Lambertenghi ; Levis, Alessandro ; Parvis, Guido ; Pavone, Enzo ; Salvi, Ravia ; Sborgia, Marco ; Gallo, Eugenio. / High dose sequential chemotherapy with autologous transplantation versus dose-dense chemotherapy MegaCEOP as first line treatment in poor-prognosis diffuse large cell lymphoma : An "Intergruppo Italiano Linfomi" randomized trial. In: Haematologica. 2005 ; Vol. 90, No. 6. pp. 793-801.
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abstract = "Background and Objectives. Poor prognosis diffuse large cell lymphoma (DLCL) responds poorly to standard chemotherapy. Randomized studies comparing high-dose chemotherapy with autologous stem-cell transplantation (ASCT) against standard chemotherapy have produced conflicting results. Dose-dense chemotherapy with granulocyte colony-stimulating factor (G-CSF) support seems to hold promise. The purpose of this multicenter, randomized trial was to compare failure-free and overall survival in patients with poor prognosis DLCL treated with high-dose sequential (HDS) chemotherapy followed by ASCT or an outpatient dose-dense chemotherapy regimen (MegaCEOP). Design and Methods. Between 1996 and 2001, 130 DLCL patients, aged ≤ 60 years, with intermediate-high or high-risk disease, according to the International Prognostic Index score, and/or bone marrow involvement were enrolled. Sixty were randomized to HDS chemotherapy plus high-dose mitoxantrone and melphalan with ASCT (arm A) and 66 to the MegaCEOP regimen (6-8 courses of an escalated dose of cyclophosphamide and epirubicin plus vincristine and prednisone with G-CSF every 2-weeks) (arm B); 4 patients were considered ineligible. Results. The complete remission rate was 59{\%} in arm A and 70{\%} in arm B (p=0.18). After a median follow-up of 78 months, the 6-year failure-free survival was 45{\%} in arm A and 48{\%} in arm B (hazard ratio=1.15, 95{\%} confidence intervals =0.72-1.84, p=0.56). The 5-year overall survival was 49{\%} in arm A and 63{\%} in arm B (hazard ratio=1.67, 95{\%} confidence interval=0.98-2.85, p=0.06). Two cases of secondary acute myeloid leukemia were observed after treatment in group A. Interpretations and Conclusions. HDS and ASCT as initial therapy for patients with poor-prognosis DLCL does not provide a benefit over that of outpatient dose-dense MegaCEOP chemotherapy.",
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T1 - High dose sequential chemotherapy with autologous transplantation versus dose-dense chemotherapy MegaCEOP as first line treatment in poor-prognosis diffuse large cell lymphoma

T2 - An "Intergruppo Italiano Linfomi" randomized trial

AU - Vitolo, Umberto

AU - Liberati, Anna Marina

AU - Cabras, Maria Giuseppina

AU - Federico, Massimo

AU - Angelucci, Emanuele

AU - Baldini, Luca

AU - Boccomini, Carola

AU - Brugiatelli, Maura

AU - Calvi, Roberta

AU - Ciccone, Giovannino

AU - Genua, Angelo

AU - Deliliers, Giorgio Lambertenghi

AU - Levis, Alessandro

AU - Parvis, Guido

AU - Pavone, Enzo

AU - Salvi, Ravia

AU - Sborgia, Marco

AU - Gallo, Eugenio

PY - 2005/6

Y1 - 2005/6

N2 - Background and Objectives. Poor prognosis diffuse large cell lymphoma (DLCL) responds poorly to standard chemotherapy. Randomized studies comparing high-dose chemotherapy with autologous stem-cell transplantation (ASCT) against standard chemotherapy have produced conflicting results. Dose-dense chemotherapy with granulocyte colony-stimulating factor (G-CSF) support seems to hold promise. The purpose of this multicenter, randomized trial was to compare failure-free and overall survival in patients with poor prognosis DLCL treated with high-dose sequential (HDS) chemotherapy followed by ASCT or an outpatient dose-dense chemotherapy regimen (MegaCEOP). Design and Methods. Between 1996 and 2001, 130 DLCL patients, aged ≤ 60 years, with intermediate-high or high-risk disease, according to the International Prognostic Index score, and/or bone marrow involvement were enrolled. Sixty were randomized to HDS chemotherapy plus high-dose mitoxantrone and melphalan with ASCT (arm A) and 66 to the MegaCEOP regimen (6-8 courses of an escalated dose of cyclophosphamide and epirubicin plus vincristine and prednisone with G-CSF every 2-weeks) (arm B); 4 patients were considered ineligible. Results. The complete remission rate was 59% in arm A and 70% in arm B (p=0.18). After a median follow-up of 78 months, the 6-year failure-free survival was 45% in arm A and 48% in arm B (hazard ratio=1.15, 95% confidence intervals =0.72-1.84, p=0.56). The 5-year overall survival was 49% in arm A and 63% in arm B (hazard ratio=1.67, 95% confidence interval=0.98-2.85, p=0.06). Two cases of secondary acute myeloid leukemia were observed after treatment in group A. Interpretations and Conclusions. HDS and ASCT as initial therapy for patients with poor-prognosis DLCL does not provide a benefit over that of outpatient dose-dense MegaCEOP chemotherapy.

AB - Background and Objectives. Poor prognosis diffuse large cell lymphoma (DLCL) responds poorly to standard chemotherapy. Randomized studies comparing high-dose chemotherapy with autologous stem-cell transplantation (ASCT) against standard chemotherapy have produced conflicting results. Dose-dense chemotherapy with granulocyte colony-stimulating factor (G-CSF) support seems to hold promise. The purpose of this multicenter, randomized trial was to compare failure-free and overall survival in patients with poor prognosis DLCL treated with high-dose sequential (HDS) chemotherapy followed by ASCT or an outpatient dose-dense chemotherapy regimen (MegaCEOP). Design and Methods. Between 1996 and 2001, 130 DLCL patients, aged ≤ 60 years, with intermediate-high or high-risk disease, according to the International Prognostic Index score, and/or bone marrow involvement were enrolled. Sixty were randomized to HDS chemotherapy plus high-dose mitoxantrone and melphalan with ASCT (arm A) and 66 to the MegaCEOP regimen (6-8 courses of an escalated dose of cyclophosphamide and epirubicin plus vincristine and prednisone with G-CSF every 2-weeks) (arm B); 4 patients were considered ineligible. Results. The complete remission rate was 59% in arm A and 70% in arm B (p=0.18). After a median follow-up of 78 months, the 6-year failure-free survival was 45% in arm A and 48% in arm B (hazard ratio=1.15, 95% confidence intervals =0.72-1.84, p=0.56). The 5-year overall survival was 49% in arm A and 63% in arm B (hazard ratio=1.67, 95% confidence interval=0.98-2.85, p=0.06). Two cases of secondary acute myeloid leukemia were observed after treatment in group A. Interpretations and Conclusions. HDS and ASCT as initial therapy for patients with poor-prognosis DLCL does not provide a benefit over that of outpatient dose-dense MegaCEOP chemotherapy.

KW - Autologous transplantation

KW - Dose-dense chemotherapy

KW - Poor-prognosis DLCL

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