Epstein-Barr virus-associated post-transplant lymphoproliferative disease during dasatinib treatment occurred 10 years after umbilical cord blood transplantation

Abstract

Post-transplant lymphoproliferative disease (PTLD) is defined as a lymphoma that occurs after solid-organ or hematopoietic stem-cell transplantation (HSCT), caused by immunosuppression and Epstein-Barr virus (EBV) reactivation. It is an important post-transplant complication that can be fatal. After HSCT, most PTLD occurs within 2 years. Recent evidence suggests that tyrosine kinase inhibitors (TKIs) are expected to be effective maintenance therapy after HSCT for Philadelphia chromosome-positive leukemia. However, it is unclear whether the use of TKIs might pose a risk of developing PTLD after HSCT. We present the first case of late-onset PTLD during dasatinib treatment, which occurred 10 years after umbilical cord blood transplantation (CBT). A 59-year-old man who received CBT for chronic myeloid leukemia blast phase needed long-term dasatinib therapy for molecular relapse. Ten years after CBT, he developed diffuse-large B-cell lymphoma (DLBCL). We observed chimerism of the DLBCL sample, which indicated complete donor type and EBV-DNA, and the patient was diagnosed with PTLD. Because of treatment resistance, he died 6 months after PTLD onset. Although he received no long-term administration of immunosuppressive agents, he received long-term dasatinib treatment, which suggests that prolonged dasatinib use after CBT caused EBV reactivation and led to PTLD. Our case suggests that the potential contribution of molecular-targeted agents after HSCT to the development of PTLD should be carefully considered.

Keywords: Epstein–Barr virus; Post-transplant lymphoproliferative disease; dasatinib.