Increased Incidence of Hodgkin's Disease After Allogeneic Bone Marrow Transplantation

Abstract

PURPOSE: Immune dysregulation associated with allogeneic bone marrow transplantation (BMT) is linked to an increased risk of posttransplant lymphoproliferative disorders (PTLD); however, reports of Hodgkin's disease (HD) after transplantation are rare. PATIENTS AND METHODS: We evaluated the risk of HD among 18,531 persons receiving allogeneic BMT between 1964 and 1992 at 235 centers. The number of HD cases was compared with that expected in the general population. Risk factors were identified using Poisson regression and a nested case-control study. RESULTS: Risk of HD was increased in the postBMT population compared with the general population with an observed-to-expected incidence ratio (O/E) of 6.2 (observed cases, n = 8; 95% confidence interval [CI], 2.7 to 12). A significantly increased risk of HD remained after excluding two human immunodeficiency virus–positive patients (observed cases, n = 6; O/E = 4.7, 95% CI, 1.7 to 10.3). Mixed cellularity subtype predominated (five of eight cases, 63%). Five of six assessable cases contained Epstein-Barr virus (EBV) genome. Posttransplant HD differed from PTLD by later onset (> 2.5 years) and lack of association with established risk factors (such as T-cell depletion and HLA disparity). Patients with HD were more likely than matched controls to have had grade 2 to 4 acute graft-versus-host disease (GVHD), required therapy for chronic GVHD, or both (P = .002), although analysis included small numbers of patients. CONCLUSION: The increased incidence of HD among BMT recipients adds support to current theories which link overstimulation of cell-mediated immunity and exposure to EBV with various subtypes of HD. The long latency of HD after transplant and lack of association with risk factors for PTLD is noteworthy and should be explored further for possible insights into pathogenesis.