Survival outcomes of allogeneic hematopoietic cell transplants with EBV-positive or EBV-negative post-transplant lymphoproliferative disorder, A CIBMTR study

Abstract

Background: Post-transplant lymphoproliferative disorders (PTLD) are associated with significant morbidity and mortality following allogeneic hematopoietic cell transplant (alloHCT). Although most PTLD is EBV-positive (EBV^pos ), EBV-negative (EBV^neg ) PTLD is reported, yet its incidence and clinical impact remain largely undefined. Furthermore, factors at the time of transplant impacting survival following PTLD are not well described.

Methods: Between 2002 and 2014, 432 cases of PTLD following alloHCT were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). After exclusions, 267 cases (EBV^pos = 222, 83%; EBV^neg = 45, 17%) were analyzed.

Results: Two hundred and eight patients (78%) received in vivo T-cell depletion (TCD) with either anti-thymocyte globulin (ATG) or alemtuzumab. Incidence of PTLD was highest using umbilical cord donors (UCB, 1.60%) and lowest using matched related donors (MRD, 0.40%). Clinical features and histology did not significantly differ among EBV^pos or EBV^neg PTLD cases except that absolute lymphocyte count recovery was slower, and CMV reactivation was later in EBV^neg PTLD [EBV^pos 32 (5-95) days versus EBV^neg 47 (10-70) days, P = .016]. There was no impact on survival by EBV status in multivariable analysis [EBV^neg RR 1.42, 95% CI 0.94-2.15, P = .097].

Conclusions: There is no difference in survival outcomes for patients with EBV^pos or EBV^neg PTLD occurring following alloHCT and 1-year survival is poor. Features of conditioning and use of serotherapy remain important.

Keywords: Epstein-Barr virus; allogeneic hematopoietic cell transplant; post-transplant lymphoproliferative disorder.