title: Evaluation of clinical and biological prognostic factors in relapsed or refractory diffuse large B-cell lymphoma patients after previous treatment with rituximab and chemotherapy: results of the PRO-R-IPI study.
abstract: BACKGROUND
  Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity, showing a highly variable outcome. In patients with DLBCL relapsed/refractory to first-line treatment with rituximab the usefulness of the revised International Prognostic Index (R-IPI) as a prognostic tool remains unexplored. Some biological parameters (B-cell lymphoma 6 [Bcl-6], Bcl-2, p53, and multiple myeloma 1 [MUM1]) and blood populations (lymphocyte and monocyte counts) have been described as International Prognostic Index-independent prognostic factors. The objective was to evaluate the R-IPI to predict the outcome of DLBCL patients at the time of relapse after a front-line treatment with chemotherapy and rituximab and to establish in this population the relationship between biological parameters and outcome.
  
  
  METHODS
  We included patients with refractory/relapsed DLBCL after first-line treatment with rituximab-containing regimens; patients must have already finished a rescue treatment also including rituximab. Immunohistochemical assessment of Bcl-2, Bcl-6, p53, and MUM1 expression were undertaken in available biopsies. R-IPI factors were identified from the clinical data at diagnosis and at relapse. Response was assessed using National Cancer Institute-sponsored Working Group guidelines.
  
  
  RESULTS
  R-IPI prognosis at relapse was not significantly associated with overall response rate (ORR) after Rituximab-chemotherapy rescue therapy. None of the immunohistochemical parameters analyzed correlated with rescue therapy results. In contrast, patients with absolute lymphocyte count (ALC) ≥ 1 × 10(9)/L at relapse were more likely to respond than patients with ALC < 1 × 10(9)/L (P = .05).
  
  
  CONCLUSIONS
  The R-IPI score calculated at relapse could not predict the ORR to second-line treatment. Lymphopenia is a simple and useful predictor for outcome in relapsed/refractory DLBCL and the only prognostic factor that in our hands could predict the overall response to a second-line treatment with rituximab and chemotherapy.
authors.affiliation: Clínica Universidad de Navarra, Pamplona, Spain. Electronic address: cpanizo@unav.es.
authors.forename: Carlos
authors.initials: C
authors.lastname: Panizo
authors.affiliation: Hospital Vall d' Hebrón, Barcelona, Spain.
authors.forename: Anny Jaramillo
authors.initials: AJ
authors.lastname: Rodríguez
authors.affiliation: Hospital Clínico de Barcelona, Barcelona, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Gutiérrez
authors.affiliation: Hospital Clínico Universitario, Valladolid, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Díaz
authors.affiliation: Institut Catalá d'Oncología-Hospital Duran i Reynals, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: González-Barca
authors.affiliation: M.D. Anderson, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: de Oña
authors.affiliation: Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Grande
authors.affiliation: Hospital German Trias I Pujol, Badalona, Spain.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Sancho
authors.affiliation: Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: María Flor
authors.initials: MF
authors.lastname: García-Álvarez
authors.affiliation: Hospital del Mar, Barcelona, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Sánchez-González
authors.affiliation: Hospital Universitario Fundación Alcorcón, Madrid, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Peñalver
authors.affiliation: Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Jimena
authors.initials: J
authors.lastname: Cannata
authors.affiliation: Hospital Carlos Haya, Málaga, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Espeso
authors.affiliation: Hospital Severo Ochoa, Madrid, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Requena
authors.affiliation: Institut Catalá d'Oncología, Girona, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Gardella
authors.affiliation: Hospital Ciudad de Jaén, Jaén, Spain.
authors.forename: Soledad
authors.initials: S
authors.lastname: Durán
authors.affiliation: Hospital de Cabueñes, Asturias, Spain.
authors.forename: Ana Pilar
authors.initials: AP
authors.lastname: González
authors.affiliation: Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Alfonso
authors.affiliation: Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Caballero
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001706:Biopsy; D003430:Cross-Sectional Studies; D019008:Drug Resistance, Neoplasm; D005260:Female; D019254:Genes, bcl-2 / Q000235:genetics; D006801:Humans; D050835:Interferon Regulatory Factors / Q000378:metabolism; D018655:Lymphocyte Count; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D011379:Prognosis; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000378:metabolism; D000069283:Rituximab / Q000627:therapeutic use*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000099218:Interferon Regulatory Factor-4
chemical_list: D000970:Antineoplastic Agents; D050835:Interferon Regulatory Factors; D010446:Peptide Fragments; D051560:Proto-Oncogene Proteins c-bcl-6; D000069283:Rituximab; D016159:Tumor Suppressor Protein p53; D000099218:Interferon Regulatory Factor-4; C509415:p53 protein (325-355), human
keywords: International Prognostic Index; Non-Hodgkin lymphoma; Prognosis; Relapse