title: Increasing incidence of late second malignancies after conditioning with cyclophosphamide and total-body irradiation and autologous bone marrow transplantation for non-Hodgkin's lymphoma.
abstract: OBJECTIVE
  Although the risk of myelodysplastic syndrome (MDS) has been well-described following autologous bone marrow transplantation (ABMT), the risk of solid tumors has been poorly characterized. We report the incidence and outcome of solid tumors at 10-year follow-up in a large cohort of uniformly treated patients who underwent ABMT for non-Hodgkin's lymphoma (NHL).
  
  
  METHODS
  Between 1982 and 1997, 605 patients underwent ABMT for B-cell NHL, with uniform conditioning with cyclophosphamide and total-body irradiation followed by reinfusion of autologous bone marrow purged with anti-B-cell monoclonal antibodies. Current information on relapse of disease and second malignancies was obtained via an institutional review board-approved questionnaire sent to the referring oncologists.
  
  
  RESULTS
  Forty-two solid tumors, six non-MDS hematologic malignancies, 39 nonmelanoma skin cancers, and 68 cases of MDS/acute myelogenous leukemia (AML) were observed at a median follow-up of 9.5 years. A cumulative incidence model using death as a competing risk found that the 10-year incidence of second malignancy is 21%, with 10.0% non-MDS malignancies. The projected incidence of all malignancies at 15 years is 29%. The principal risk factor for second malignancy is increased age at ABMT (P = .0002). In the entire cohort, 9.6% of patients have died of second malignancy.
  
  
  CONCLUSIONS
  Lengthy follow-up demonstrates a significant incidence of second malignancies after ABMT for NHL. Although the incidence of MDS/AML starts to plateau, the incidence of solid tumors continues to rise. Second malignancies are responsible for a significant fraction of overall mortality following ABMT.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Brown
authors.forename: Heather
authors.initials: H
authors.lastname: Yeckes
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Friedberg
authors.forename: Donna
authors.initials: D
authors.lastname: Neuberg
authors.forename: Helen
authors.initials: H
authors.lastname: Kim
authors.forename: Lee M
authors.initials: LM
authors.lastname: Nadler
authors.forename: Arnold S
authors.initials: AS
authors.lastname: Freedman
mesh_terms: D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000209:etiology*; D012307:Risk Factors; D014182:Transplantation, Autologous; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide