title: Patients with high-risk aggressive lymphoma treated with frontline intensive chemotherapy and autografting: evidence of marked differences in outcome between patients with age-adjusted International Prognostic Index scores 2 and 3.
abstract: BACKGROUND
  The goal of the current study was to evaluate the impact of presentation with an age-adjusted International Prognostic Index (aaIPI) score of 2 or 3 on patients with high-risk aggressive lymphoma who are treated with frontline intensive chemotherapy and autografting.
  
  
  METHODS
  Sixty-nine consecutive patients (median age, 40 years) with either B-cell (n = 60) or non-B-cell (n = 9) aggressive lymphoma were treated with high-dose sequential (HDS) chemotherapy and peripheral blood progenitor cell (PBPC) autografting. The patients who were examined had poor prognoses, with aaIPI scores of 2 (n = 37) or 3 (n = 32). The original treatment regimen, sequential delivery of cyclophosphamide, methotrexate, and etoposide, followed by PBPC autografting (o-HDS), was used in the first 32 patients; the program was intensified by the addition of a course of high-dose cytosine arabinoside (C-HDS) in the next 37 patients.
  
  
  RESULTS
  There were 4 toxicity-related deaths-2 in each aaIPI subgroup (treatment-related mortality, 5.8%). The complete remission rate was significantly higher among patients with an aaIPI score of 2 (n = 32 [86%]) compared with those with an aaIPI score of 3 (n = 13 [41%]; P < 0.001). Patients with an aaIPI score of 2 had significantly better outcomes than did patients with an aaIPI score of 3 in terms of both overall survival (78% vs. 34% at 8 years; P < 0.001) and event-free survival (72% vs. 28% at 8 years; P < 0.001). Similar results were observed when the analysis was limited to the 60 patients with B-cell-derived lymphoma. No significant differences in outcome between patients receiving o-HDS and patients receiving C-HDS were observed. Multivariate analysis demonstrated that an aaIPI score of 3 was the only parameter that was significantly associated with poor overall and event-free survival.
  
  
  CONCLUSIONS
  Age-adjusted International Prognostic Index score is applicable to patients with aggressive lymphoma who are treated with frontline intensive chemotherapy and autografting. In addition, upfront use of HDS chemotherapy appears to be beneficial to patients with an aaIPI score of 2 but not to those with an aaIPI score of 3.
authors.affiliation: Dipartimento di Medicina Oncologia Sperimentale, Divisione Universitaria di Ematologia, Azienda Ospedaliera San Giovanni Battista, Via Genova 3, 10126 Turin, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cuttica
authors.forename: Francesco
authors.initials: F
authors.lastname: Zallio
authors.forename: Marco
authors.initials: M
authors.lastname: Ladetto
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Nicola
authors.forename: Daniele
authors.initials: D
authors.lastname: Caracciolo
authors.forename: Michele
authors.initials: M
authors.lastname: Magni
authors.forename: Carlo
authors.initials: C
authors.lastname: Marinone
authors.forename: Maria
authors.initials: M
authors.lastname: Dell'Aquila
authors.forename: Michela
authors.initials: M
authors.lastname: Rosace
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pileri
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Gianni
authors.forename: Corrado
authors.initials: C
authors.lastname: Tarella
mesh_terms: D000328:Adult; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D036102:Peripheral Blood Stem Cell Transplantation; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D003561:Cytarabine; D005047:Etoposide; D003520:Cyclophosphamide; D008727:Methotrexate