title: Rate of primary refractory disease in B and T-cell non-Hodgkin's lymphoma: correlation with long-term survival.
abstract: BACKGROUND
  Primary refractory disease is a main challenge in the management of non-Hodgkin's Lymphoma (NHL). This survey was performed to define the rate of refractory disease to first-line therapy in B and T-cell NHL subtypes and the long-term survival of primary refractory compared to primary responsive patients.
  
  
  METHODS
  Medical records were reviewed of 3,106 patients who had undergone primary treatment for NHL between 1982 and 2012, at the Hematology Centers of Torino and Bergamo, Italy. Primary treatment included CHOP or CHOP-like regimens (63.2%), intensive therapy with autograft (16.9%), or other therapies (19.9%). Among B-cell NHL, 1,356 (47.8%) received first-line chemotherapy with rituximab. Refractory disease was defined as stable/progressive disease, or transient response with disease progression within six months.
  
  
  RESULTS
  Overall, 690 (22.2%) patients showed primary refractory disease, with a higher incidence amongst T-cell compared to B-cell NHL (41.9% vs. 20.5%, respectively, p<0.001). Several other clinico-pathological factors at presentation were variably associated with refractory disease, including histological aggressive disease, unfavorable clinical presentation, Bone Marrow involvement, low lymphocyte/monocyte ration and male gender. Amongst B-cell NHL, the addition of rituximab was associated with a marked reduction of refractory disease (13.6% vs. 26.7% for non-supplemented chemotherapy, p<0.001). Overall, primary responsive patients had a median survival of 19.8 years, compared to 1.3 yr. for refractory patients. A prolonged survival was consistently observed in all primary responsive patients regardless of the histology. The long life expectancy of primary responsive patients was documented in both series managed before and after 2.000. Response to first line therapy resulted by far the most predictive factor for long-term outcome (HR for primary refractory disease: 16.52, p<0.001).
  
  
  CONCLUSIONS
  Chemosensitivity to primary treatment is crucial for the long-term survival in NHL. This supports the necessity of studies aimed to early identify refractory disease and to develop different treatment strategies for responsive and refractory patients.
authors.affiliation: Department of Biotechnology and Life Sciences, University of Torino, Torino, Italy; Hematology and Cell Therapy Division, Mauriziano Hospital, Torino, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Tarella
authors.affiliation: Department of Biotechnology and Life Sciences, University of Torino, Torino, Italy; Hematology and Cell Therapy Division, Mauriziano Hospital, Torino, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Gueli
authors.affiliation: Hematology and Bone Marrow Transplant Units, A. O. Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Delaini
authors.affiliation: Hematology and Bone Marrow Transplant Units, A. O. Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Hematology and Bone Marrow Transplant Units, A. O. Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Barbui
authors.affiliation: Hematology and Bone Marrow Transplant Units, A. O. Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gritti
authors.affiliation: Hematology and Bone Marrow Transplant Units, A. O. Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Boschini
authors.affiliation: Department of Biotechnology and Life Sciences, University of Torino, Torino, Italy; Division of Hematology I, A. O. Città della Salute, Torino, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Caracciolo
authors.affiliation: Department of Biotechnology and Life Sciences, University of Torino, Torino, Italy; Hematology and Cell Therapy Division, Mauriziano Hospital, Torino, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bruna
authors.affiliation: Department of Biotechnology and Life Sciences, University of Torino, Torino, Italy; Hematology and Cell Therapy Division, Mauriziano Hospital, Torino, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Ruella
authors.affiliation: Department of Biotechnology and Life Sciences, University of Torino, Torino, Italy; Hematology and Cell Therapy Division, Mauriziano Hospital, Torino, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Gottardi
authors.affiliation: Division of Nuclear Medicine, University of Torino, Torino, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Passera
authors.affiliation: Division of Hematology I, A. O. Città della Salute, Torino, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D016399:Lymphoma, T-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents