Risk of lymphoproliferative disorders after bone marrow transplantation: Amulti-institutional study

We evaluated 18,014 patients who underwent allogeneic hone marrow transplan tation (BMT) at 235 centers worldwide to examine the incidence of and risk factors for posttransplant lymphoproliferative disorders ( PTLD). PTLD deve loped in 78 recipients, with 64 cases occurring less than 1 year after tran splantation. The cumulative incidence of PTLD was 1.0% +/- 0.3% at 10 years . incidence was highest 1 to 5 months posttransplant (120 cases/10,000 pati ents/yr) followed by a steep decline to less than 5/10,000/yr among greater than or equal to 1-year survivors. In multivariate analyses, risk of early -onset PTLD (<1 year) was strongly associated (P < .0001) with unrelated or human leukocyte antigen (HLA) mismatched related donor (relative risk [RR] = 4.1), T-cell depletion of donor marrow (RR = 12.7), and use of antithymo cyte globulin (RR = 6.4) or anti-CD3 monoclonal antibody (RR = 43.2) for pr ophylaxis or treatment of acute graft-versus-host disease (GVHD). There was a weaker association with the occurrence of acute GVHD grades II to IV (RR = 1.9, P = .02) and with conditioning regimens that included radiation (RR = 2.9, P = .02). Methods of T-cell depletion that selectively targeted T c ells or T plus natural killer (NK) cells were associated with markedly high er risks of PTLD than methods that removed both T and B cells, such as the CAMPATH-1 monoclonal antibody or elutriation (P = .009). The only risk fact or identified for late-onset PTLD was extensive chronic GVHD (RR = 4.0, P = .01). Rates of PTLD among patients with 2 or greater than or equal to 3 ma jor risk factors were 8.0% +/- 2.9% and 22% +/- 17.9%, respectively. We con clude that factors associated with altered immunity and T-cell regulatory m echanisms are predictors of both early- and late-onset PTLD. This is a US government work. There are no restrictions on its use.