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. 2005 Jun;90(6):793-801.

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 < or = 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.

Interpretation 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Epirubicin / administration & dosage
  • Female
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Male
  • Melphalan / administration & dosage
  • Middle Aged
  • Mitoxantrone / administration & dosage
  • Prednisone / administration & dosage
  • Prognosis
  • Transplantation, Autologous
  • Vincristine / administration & dosage

Substances

  • Antineoplastic Agents
  • Granulocyte Colony-Stimulating Factor
  • Epirubicin
  • Vincristine
  • Cyclophosphamide
  • Mitoxantrone
  • Melphalan
  • Prednisone