New malignant diseases after allogeneic marrow transplantation for childhood acute leukemia

Purpose: To determine the incidence of and risk factors for second malignan cies after allogeneic bone mar row transplantation (BMT) far childhood leuk emia. Patients and Methods: We studied a cohort of 3,182 children diagnosed with acute leukemia before the age of 17 years who received allogeneic BMT betwe en 1964 and 1992 at 235 centers. Observed second cancers were compared with expected cancers in an age and sex-matched general population. Risks facto rs were evaluated using Poisson regression. Results: Twenty-five solid tumors and 20 posttransplant lymphoproliferative disorders (PTLDs) were observed compared with 1.0 case expected (P <.001), Cumulative risk of solid cancers increased sharply to 11.0% (95% confidenc e interval, 2.3% to 19.8%) at 15 years and was highest among children at ag es younger than 5 years at transplantation. Thyroid and brain cancers (n = 14) accounted for most of the strong age trend; many of these patients rece ived cranial irradiation before BMT, Multivariate analyses showed increased solid tumor risks associated with high-dose total-body irradiation (relati ve risk [RR] = 3.1) and younger age at transplantation (RR = 3.7), whereas chronic graft-versus-host disease was associated with a decreased risk (RR = 0.2). Risk factors for PTLD included chronic graft-versus-host disease (R R = 6.5), unrelated or HLA-disparate related donor (RR = 7.5), T-cell-deple ted graft (RR = 4.8), and antithymocyte globulin therapy (RR = 3.1). Conclusion: Long-term survivors of BMT for childhood leukemia have an incre ased risk of solid cancers and PTLDs, related to both transplant therapy an d treatment given before BMT. Transplant recipients, especially those given radiation, should be monitored closely for second cancers. (C) 2000 by Ame rican Society of Clinical Oncology.