title: Estimating late adverse events using competing risks after autologous stem-cell transplantation in aggressive non-Hodgkin lymphoma patients.
abstract: BACKGROUND
  Consolidative autologous stem-cell transplantation (ASCT) is a valuable option in high-risk or disease recurrence large-cell non-Hodgkin lymphoma patients (NHL); however, its long-term toxicity must still be assessed.
  
  
  METHODS
  Among the 439 lymphoma patients transplanted at our institution from January 1, 1993, to January 1, 2002, 158 exhibited aggressive NHL. The median age of the patients was 46 years (range, 18-69), 98 males and 60 females. Ninety (57%) patients received first-line ASCT. The median number of prior chemotherapy regimens was 2 (range, 1-10). Thirty-eight (24%) patients received total body irradiation conditioning. Here we report the adverse events which occurred at least 30 days after ASCT and before disease recurrence.
  
  
  RESULTS
  After a median follow-up of 3 years, the overall and disease-free survival rates were 61% and 55%, respectively. Sixty-eight late adverse events affected 43 (27%) patients, leading to a cumulative incidence of 34% at 3 years. Infections were the most frequent adverse events (n = 13), followed by neurologic (n = 12), pulmonary (n = 6), or cardiovascular (n = 4). Eight malignancies were diagnosed (six solid, two hematologic), leading to a cumulative incidence of 3.7% at 3 years. Taking into account the competing risks, multivariate analysis revealed that the number of progressions (relative risk [RR] = 2.68) and a mitoxantrone-containing conditioning regimen (RR = 2.98) significantly increased the incidence of late toxicity.
  
  
  CONCLUSIONS
  ASCT is effective in patients with aggressive NHL with a poor prognosis. However, careful long-term follow-up of survivors is recommended because of the increase in malignant and nonmalignant toxicities.
authors.affiliation: Departement of Medicine, Institut Gustave Roussy, Villejuif, France.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Ruiz-Soto
authors.forename: Guillaume
authors.initials: G
authors.lastname: Sergent
authors.forename: Christian
authors.initials: C
authors.lastname: Gisselbrecht
authors.forename: Jerome
authors.initials: J
authors.lastname: Larghero
authors.forename: Marjan
authors.initials: M
authors.lastname: Ertault
authors.forename: Christophe
authors.initials: C
authors.lastname: Hennequin
authors.forename: Julien
authors.initials: J
authors.lastname: Manson
authors.forename: Eric
authors.initials: E
authors.lastname: de Kerviler
authors.forename: Josette
authors.initials: J
authors.lastname: Briere
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mounier
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002423:Cause of Death; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015994:Incidence; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D018570:Risk Assessment; D016879:Salvage Therapy; D012720:Severity of Illness Index; D017678:Sex Distribution; D016019:Survival Analysis; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome