Second malignancy following high-dose therapy and autologous stem cell transplantation: incidence and risk factor analysis

To establish incidence and risk factors for development of second malignant neoplasms after high-dose chemo/radiotherapy (HDT) and autologous hematopoietic stem cell transplantation (AHSCT), the case files of 800 consecutive patients who underwent AHSCT at our institution between June 1982 and December 2000 were reviewed. In all, 26 patients developed 29 second malignancies (nine myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML), 16 solid tumors and four lymphoproliferative disorders (LPDs)) for a 15-year cumulative incidence of 11% (95% confidence interval (CI), 5-18%). These second tumors occurred at a median of 68 (range 1.5-177) months following AHSCT. The relative risk (RR) compared to the general population of developing a second malignancy following AHSCT was 3.3 (CI 2.2-4.7) P < 0.001. The RR of developing MDS/AML, LPD and a solid tumor was 47.2 (CI 21.5-89.5) P < 0.001, 8.1 (2.2-20.7) P = 0.002 and 1.98 (1.1-3.2) P = 0.009, respectively. In multivariate analysis, age greater than or equal to35 years at the time of AHSCT (P = 0.001) and an interval from diagnosis to AHSCT greater than or equal to36 months (P = 0.03) were associated with a greater risk of developing a second malignancy. Patients who have undergone HDT and AHSCT are at significant risk for developing a second malignancy and should receive indefinite follow-up.