title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Postinduction BCL2/IgH major break point status in BM/PB is not useful for decisions on subsequent therapy for patients with relapsed/resistant FL.
authors.affiliation: Department of Hematology F4-224, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. M.H.vanOers@AMC.UVA.NL
authors.forename: Marinus H J
authors.initials: MH
authors.lastname: van Oers
authors.forename: Evelyn
authors.initials: E
authors.lastname: Tönnissen
authors.forename: Martine
authors.initials: M
authors.lastname: Van Glabbeke
authors.forename: Livia
authors.initials: L
authors.lastname: Giurgea
authors.forename: Joop H
authors.initials: JH
authors.lastname: Jansen
authors.forename: Richard
authors.initials: R
authors.lastname: Klasa
authors.forename: Robert E
authors.initials: RE
authors.lastname: Marcus
authors.forename: Max
authors.initials: M
authors.lastname: Wolf
authors.forename: Eva
authors.initials: E
authors.lastname: Kimby
authors.forename: Andrej
authors.initials: A
authors.lastname: Vranovsky
authors.forename: Harald
authors.initials: H
authors.lastname: Holte
authors.forename: Anton
authors.initials: A
authors.lastname: Hagenbeek
authors.forename: Bert A
authors.initials: BA
authors.lastname: van der Reijden
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001315:Australia; D002170:Canada; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D005060:Europe; D015972:Gene Expression Regulation, Neoplastic; D050438:Genes, Immunoglobulin Heavy Chain; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D009520:New Zealand; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011241:Prednisone / Q000008:administration & dosage; D016016:Proportional Hazards Models; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D013019:South Africa; D013997:Time Factors; D017211:Treatment Failure; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone