Marked increased risk of Epstein-Barr virus-related complications with the addition of antithymocyte globulin to a nonmyeloablative conditioning prior to unrelated umbilical cord blood transplantation

Umbilical cord blood (UCB) is increasingly used as an alternative source of hematopoietic stem cells for transplantation for patients who lack a suitable sibling donor. Despite concerns about a possible increased risk of Epstein-Barr virus (EBV) posttransplantation lymphoproliferative disorder (PTLD) after UCB transplantation, early reports documented rates of PTLD comparable to those reported after HLA-matched unrelated marrow myeloablative (MA) transplantations. To further investigate the incidence of EBV PTLD after UCB transplantation and potential risk factors, we evaluated the incidence of EBV-related complications in 335 patients undergoing UCB transplantation with an MA or nonmyeloablative (NMA) preparative regimen. The incidence of EBV-related complications was a 4.5% overall, 3.3% for MA transplantations, and 7% for NMA transplantations. However, the incidence of EBV-related complications was significantly higher in a subset of patients treated with an NMA preparative regimen that included antithymocyte globulin (ATG) versus those that did not (21% vs 2%; P < .01). Nine of 11 patients who developed EBV PTLD were treated with rituximab (anti-CD20 antibody), with the 5 responders being alive and disease free at a median of 26 months. Use of ATG in recipients of an NMA preparative regimen warrants close monitoring for evidence of EBV reactivation and potentially preemptive therapy with rituximab.