BCL-2/IgH polymerase chain reaction status at the end of induction treatment is not predictive for progression-free survival in relapsed/resistant follicular lymphoma: results of a prospective randomized EORTC 20981 phase III intergroup study

J Clin Oncol. 2010 May 1;28(13):2246-52. doi: 10.1200/JCO.2009.25.0852. Epub 2010 Apr 5.


Purpose: The prognostic value of residual BCL2/immunoglobulin heavy chain (BCL2/IgH) -positive cells in peripheral blood (PB) or bone marrow (BM) after induction treatment in follicular lymphoma (FL) is still controversial. In a prospective randomized phase III intergroup trial of 465 patients with relapsed/resistant follicular lymphoma (FL), we showed that addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone induction results in increased overall and complete response rates, and that rituximab maintenance strongly improves median progression-free survival (PFS) as well as overall survival. Here, we studied whether BCL2/IgH major break point levels in PB/BM correlated with response rates/quality for the induction phase and PFS for the maintenance phase.

Patients and methods: Samples were obtained before and after induction therapy and at the end of the 2 years maintenance/observation period. BCL2/IgH major break point-positive cells were quantified by genomic quantitative polymerase chain reaction in 792 samples from 238 patients.

Results: Pretreatment BCL2/IgH levels had no significant prognostic value for overall response or complete remission rates after induction treatment, but pretreatment positive BM results had an adverse prognostic value for PFS from first randomization (P = .023). Importantly, BCL2/IgH levels at the end of induction treatment had no prognostic value for PFS from second randomization. The highly significant improved PFS by rituximab maintenance was observed in both BCL2/IgH PB/BM-positive and -negative groups.

Conclusion: Postinduction BCL2/IgH major break point status in BM/PB is not useful for decisions on subsequent therapy for patients with relapsed/resistant FL.

Publication types

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

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Australia
  • Canada
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Drug Resistance, Neoplasm
  • Europe
  • Gene Expression Regulation, Neoplastic*
  • Genes, Immunoglobulin Heavy Chain*
  • Genetic Testing / methods*
  • Humans
  • Kaplan-Meier Estimate
  • Logistic Models
  • Lymphoma, Follicular / drug therapy*
  • Lymphoma, Follicular / genetics
  • Lymphoma, Follicular / mortality
  • New Zealand
  • Polymerase Chain Reaction*
  • Predictive Value of Tests
  • Prednisone / administration & dosage
  • Proportional Hazards Models
  • Prospective Studies
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Recurrence
  • Risk Assessment
  • Risk Factors
  • South Africa
  • Time Factors
  • Treatment Failure
  • Vincristine / administration & dosage


  • Proto-Oncogene Proteins c-bcl-2
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • CHOP protocol