title: Outcome determinants for transformed indolent lymphomas treated with or without autologous stem-cell transplantation.
abstract: BACKGROUND
  Transformation of indolent lymphomas (IL) to an aggressive histology (TIL) often results in a rapid clinical course, treatment refractoriness and shortened survival. Although rituximab-containing regimens (R-chemo) have become standard of care in CD20-positive TIL, the role of autologous stem-cell transplantation (ASCT) is still debated. The purpose of this study was to determine whether the outcome of TIL patients improved if they, at transformation, also received ASCT. Furthermore, we investigated the outcome of cases with histologically low- and high-grade components diagnosed either simultaneously or after a period of overt indolent disease. We also analyzed, whether prior rituximab treatment during the indolent course of the disease affected outcome after transformation.
  
  
  METHODS
  Eighty-five patients (≤68 years) with histologically confirmed TIL were included. Five-year overall (OS) and progression-free survival (PFS) were calculated. Selected parameters were tested in a multivariate analysis. All analyses were conducted on three cohorts: (i) whole cohort (all TIL), (ii) patients with co-existing evidence of both indolent and aggressive histology at diagnosis (Composite/discordant TIL) and (iii) patients transformed after prolonged prior indolent disease (sequential TIL).
  
  
  RESULTS
  Fifty-four patients (64%) received ASCT consolidation and 31 (36%) did not. Within the 'all TIL' cohort, the 5-year OS and PFS for R-chemo + ASCT versus R-chemo alone, were 67% versus 48% (P = 0.11) and 60% versus 30% (P = 0.02), respectively. Furthermore, in 'Composite/discordant TIL' R-chemo + ASCT showed no impact on OS (76% versus 67%; P = 0.66) or PFS (71% versus 62%; P = 0.54). Conversely, R-chemo + ASCT improved the outcome of 'sequential TIL' (OS 62% versus 36%; P = 0.07; PFS 53% versus 6%; P = 0.002), regardless of prior rituximab therapy. The beneficial effect of ASCT was significantly higher in patients who had not received rituximab at IL stage.
  
  
  CONCLUSIONS
  ASCT improved the outcome in sequential, but not composite/discordant TIL. The beneficial impact of ASCT was greater in patients, who were rituximab-naïve at transformation.
authors.affiliation: Department of Hematology.
authors.forename: C
authors.initials: C
authors.lastname: Madsen
authors.affiliation: Department of Hematology.
authors.forename: M B
authors.initials: MB
authors.lastname: Pedersen
authors.affiliation: Department of Hematology.
authors.forename: M Ø
authors.initials: MØ
authors.lastname: Vase
authors.affiliation: Department of Pathology, Aarhus University Hospital, Aarhus.
authors.forename: K
authors.initials: K
authors.lastname: Bendix
authors.affiliation: Department of Pathology, Odense University Hospital, Odense.
authors.forename: M B
authors.initials: MB
authors.lastname: Møller
authors.affiliation: Department of Pathology, Aalborg University Hospital, Aalborg.
authors.forename: P
authors.initials: P
authors.lastname: Johansen
authors.affiliation: Department of Haematology, Odense University Hospital, Odense.
authors.forename: B A
authors.initials: BA
authors.lastname: Jensen
authors.affiliation: Department of Haematology, Aalborg University Hospital, Aalborg.
authors.forename: P
authors.initials: P
authors.lastname: Jensen
authors.affiliation: Department of Haematology, Odense University Hospital, Odense.
authors.forename: L
authors.initials: L
authors.lastname: Munksgaard
authors.affiliation: Department of Haematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: P D
authors.initials: PD
authors.lastname: Brown
authors.affiliation: Department of Hematology.
authors.forename: E K
authors.initials: EK
authors.lastname: Segel
authors.affiliation: Department of Hematology frandamo@rm.dk.
authors.forename: F A
authors.initials: FA
authors.lastname: d'Amore
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D003131:Combined Modality Therapy / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008223:Lymphoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab / Q000008:administration & dosage; D014182:Transplantation, Autologous
chemical_list: D000069283:Rituximab
keywords: autologous stem-cell transplantation; rituximab era; transformed indolent lymphoma