Second cancers after hematopoietic stem cell transplantation with total body irradiation conditioning regimen in hematologic disorders.

Abstract

6548 Background: Myeloablative hematopoietic stem cell transplantation (HSCT) is the treatment of choice for several malignant hematologic disorders. Long-term survivors are increasing by the improvement of treatment protocol and supportive care. The purpose of this retrospective study was to define the incidence of second cancers in a cohort of very long term survivors treated with total body irradiation (TBI) as a part of conditioning prior to HSCT. Methods: Between 1992 and 2005, 1446 patients with hematologic disorders underwent HSCT with TBI conditioning regimen. Total 780 patients with disease free at least 5 years after HSCT were evaluated. The dose of TBI was median 12 Gy. TBI was fractionated from 1.65 to 2 Gy per fraction, twice a day. The graft-versus-host disease (GVHD) prophylaxis was cyclosporine associated to methotrexate in the majority of patients. The cumulative probability of a new malignancy was estimated by Kaplan-Meier method. The log-rank test was used for statistical comparison of potential risk factors for second malignancy. Multivariate analysis was performed using Cox proportional hazard model. Results: Median age at transplantation was 30 years (range, 2 - 66). Median duration of follow up was 9.3 years (range, 5.0 – 18.0). Second cancer occurred in 17 patients. The median time from transplantation to the diagnosis of second cancer was 5.6 years. Three tongue cancers, 1 tonsil cancer, 3 thyroid cancers, 2 breast cancers, 1 colon cancer, 1 brain tumor and 2 bone tumors were detected. The posttransplant lymphoproliferative disorders were observed in 4 patients. The experience of chronic extensive GVHD was the statistically significant factor associated with an increased risk of second cancer in univariate and multivariate analysis (p < 0.0001 and p < 0.0001, respectively). Conclusions: Long term surveillance of patients undergoing HSCT is essential to detect late-developing cancers, particularly for patients who received immunosuppressive therapy for a long period by chronic extensive GVHD. Guidelines should be developed in regard to screening and prevention of second cancers for the benefit of patients.