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

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.

• Authors: Jennifer R Brown, Heather Yeckes, Jonathan W Friedberg, Donna Neuberg, Helen Kim, Lee M Nadler, Arnold S Freedman
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 23 Issue 10 Pg. 2208-14 (Apr 01 2005) ISSN: 0732-183X [Print] United States
• PMID: 15753460 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Alkylating
• Cyclophosphamide

Topics

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