Increasing incidence of late second malignancies after conditioning with cyclophosphamide and total-body irradiation and autologous bone marrow transplantation for non-Hodgkin's lymphoma

J Clin Oncol. 2005 Apr 1;23(10):2208-14. doi: 10.1200/JCO.2005.05.158. Epub 2005 Mar 7.


Purpose: 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).

Patients and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Bone Marrow Transplantation*
  • Cohort Studies
  • Cyclophosphamide / adverse effects*
  • Cyclophosphamide / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / radiotherapy*
  • Male
  • Middle Aged
  • Neoplasms / epidemiology*
  • Neoplasms / etiology*
  • Neoplasms, Second Primary / epidemiology*
  • Neoplasms, Second Primary / etiology*
  • Risk Factors
  • Transplantation, Autologous
  • Whole-Body Irradiation / adverse effects*


  • Antineoplastic Agents, Alkylating
  • Cyclophosphamide