title: Risk factors for the development of secondary malignancy after high-dose chemotherapy and autograft, with or without rituximab: a 20-year retrospective follow-up study in patients with lymphoma.
abstract: OBJECTIVE
  High-dose chemotherapy with peripheral blood progenitor cell (PBPC) autograft is effective in high-risk lymphoma, particularly with the addition of rituximab; however, it is associated with risk of secondary malignancy. These issues have been addressed in a series of 1,347 patients with lymphoma treated with a high-dose sequential (HDS) program.
  
  
  METHODS
  A total of 1,024 patients with B-cell lymphoma, 234 patients with Hodgkin's lymphoma, and 89 patients with T-cell lymphoma were treated with HDS between 1985 and 2005 at 11 Gruppo Italiano Terapie Innovative Linfomi centers. HDS was given as salvage treatment to 707 patients (52%); 655 patients (49%) received a modified HDS, with high-dose cytarabine and two consecutive PBPC harvests. Rituximab-supplemented HDS was given to 523 patients (39%).
  
  
  RESULTS
  At a median follow-up of 7 years, the median overall survival (OS) was 16.2 years; in B-cell lymphoma the OS was significantly superior with rituximab HDS compared to HDS alone. The cumulative incidence at 5 and 10 years of secondary myelodysplasia/acute leukemia (sMDS/AL) were 3.09% and 4.52%, respectively, that of solid tumors were 2.54% and 6.79%, respectively. Factors associated with sMDS/AL were male sex and use of the second harvest PBPC for the graft; factors found to be associated with solid tumor were advanced age, post-HDS radiotherapy, and rituximab addition to HDS. Despite the increased risk of solid tumors, rituximab addition to HDS was still associated with survival advantages.
  
  
  CONCLUSIONS
  This analysis has relevant implications for the design and use of intensive chemoimmunotherapy with autograft. In addition, it offers useful insights toward the understanding and prevention of tumor development.
authors.affiliation: Hematology and Cell Therapy, A.O. Mauriziano, Nuclear Medicine and Hematology, A.O.U.S. Giovanni B., Clinica Medica, A.O.U.S. Luigi-Orbassano, University of TorinoTorino, Italy. corrado.tarella@unito.it
authors.forename: Corrado
authors.initials: C
authors.lastname: Tarella
authors.forename: Roberto
authors.initials: R
authors.lastname: Passera
authors.forename: Michele
authors.initials: M
authors.lastname: Magni
authors.forename: Fabio
authors.initials: F
authors.lastname: Benedetti
authors.forename: Andrea
authors.initials: A
authors.lastname: Rossi
authors.forename: Angela
authors.initials: A
authors.lastname: Gueli
authors.forename: Caterina
authors.initials: C
authors.lastname: Patti
authors.forename: Guido
authors.initials: G
authors.lastname: Parvis
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciceri
authors.forename: Andrea
authors.initials: A
authors.lastname: Gallamini
authors.forename: Sergio
authors.initials: S
authors.lastname: Cortelazzo
authors.forename: Valerio
authors.initials: V
authors.lastname: Zoli
authors.forename: Paolo
authors.initials: P
authors.lastname: Corradini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carobbio
authors.forename: Antonino
authors.initials: A
authors.lastname: Mulé
authors.forename: Marco
authors.initials: M
authors.lastname: Bosa
authors.forename: Anna
authors.initials: A
authors.lastname: Barbui
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Nicola
authors.forename: Marco
authors.initials: M
authors.lastname: Sorio
authors.forename: Daniele
authors.initials: D
authors.lastname: Caracciolo
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Gianni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006689:Hodgkin Disease / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008223:Lymphoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016393:Lymphoma, B-Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016399:Lymphoma, T-Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000401:mortality; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D000069283:Rituximab; D018709:Statistics, Nonparametric; D033581:Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D016019:Survival Analysis; D013997:Time Factors; D014182:Transplantation, Autologous / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab