title: Standard International prognostic index remains a valid predictor of outcome for patients with aggressive CD20+ B-cell lymphoma in the rituximab era.
abstract: OBJECTIVE
  The International Prognostic Index (IPI) is widely used for risk stratification of patients with aggressive B-cell lymphoma. The introduction of rituximab has markedly improved outcome, and R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisone) has become the standard treatment for CD20(+) diffuse large B-cell lymphoma. To investigate whether the IPI has maintained its power for risk stratification when rituximab is combined with CHOP, we analyzed the prognostic relevance of IPI in three prospective clinical trials.
  
  
  METHODS
  In total, 1,062 patients treated with rituximab were included (MabThera International Trial [MInT], 380 patients; dose-escalated regimen of cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (MegaCHOEP) trial, 72 patients; CHOP + rituximab for patients older than age 60 years [RICOVER-60] trial, 610 patients). A multivariate proportional hazards modeling was performed for single IPI factors under rituximab on event-free, progression-free, and overall survival.
  
  
  RESULTS
  IPI score was significant for all three end points. Rituximab significantly improved treatment outcome within each IPI group resulting in a quenching of the Kaplan-Meier estimators. However, IPI was a significant prognostic factor in all three end points and the ordering of the IPI groups remained valid. The relative risk estimates of single IPI factors and their order in patients treated with R-CHOP were similar to those found with CHOP.
  
  
  CONCLUSIONS
  The effects of rituximab were superimposed on the effects of CHOP with no interactions between chemotherapy and antibody therapy. These results demonstrate that the IPI is still valid in the R-CHOP era.
authors.affiliation: Dipl-Math, Institute for Medical Informatics, Statistics, and Epidemiology, Universität Leipzig, Härtelstrasse 16-18, D-04107 Leipzig, Germany. Marita.Ziepert@imise.uni-leipzig.de
authors.forename: Marita
authors.initials: M
authors.lastname: Ziepert
authors.forename: Dirk
authors.initials: D
authors.lastname: Hasenclever
authors.forename: Evelyn
authors.initials: E
authors.lastname: Kuhnt
authors.forename: Bertram
authors.initials: B
authors.lastname: Glass
authors.forename: Norbert
authors.initials: N
authors.lastname: Schmitz
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
authors.forename: Markus
authors.initials: M
authors.lastname: Loeffler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003198:Computer Simulation; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006305:Health Status Indicators; D006801:Humans; D053208:Kaplan-Meier Estimate; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011241:Prednisone / Q000008:administration & dosage; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone