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. K E Y W O R D S allogeneic hematopoietic cell transplant, Epstein-Barr virus, post-transplant lymphoproliferative disorder

Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disorders after Hematopoietic Stem Cell Transplantation: Pathogenesis, Risk Factors and Clinical Outcomes

“…However, most reports analyzed EBV-negative PTLD cases occurring in SOT recipients. Although EBV-negative PTLDs occur significantly later (median onset 4-5 years) than EBV-positive PTLDs in patients after SOT, the onset time in terms of EBV positivity is not different among those after HSCT (EBV-negative cases: median onset 5 months) [86][87][88][89]. With respect to allografts, analysis of our previous data suggested that the median onset days of PTLD development was later in patients who received CB transplantation (202 days) than in those who received bone marrow or peripheral blood stem cell transplantation (111 days) [62].…”

“…Regarding the impact of EBV status on the prognosis of PTLD, although EBV-positive PTLD has a distinct genetic profiles from that of EBV-negative PTLD, EBV status does not affect the survival outcome of HSCT recipients with PTLD [88].…”

“…Typically, PTLD after HSCT develops within 1 year, before the reconstitution of EBV-specific cytotoxic T-cell immunity [52,54]. Thus, late-onset PTLD is much less common after HSCT than after SOT [85][86][87][88]. It is documented that EBV-negative PTLDs tend to occur during the late phase after transplantation.…”

Natural Killer Cells in Post-Transplant Lymphoproliferative Disorders

“…The role of NK cells in EBV-negative PTLD has been less described than in its EBV-positive counterpart. EBV-negative PTLDs have historically represented a small minority of PTLDs, but their proportion has constantly increased in recent years [ 21 ], currently representing 30–50% of PTLDs depending on different cohorts [ 20 , 21 , 61 , 62 , 63 ]. As EBV-negative PTLDs develop late after transplantation, 5–10 years or more [ 64 ], the identification of predictive biomarkers, and therefore prevention, is difficult.…”

Management of PTLD After Hematopoietic Stem Cell Transplantation: Immunological Perspectives

“…The development of EBV-PTLD after HSCT represents a life threatening event; mortality is still relevant, at 30 and 40% of diagnosed cases ( 20 , 54 ). The onset of PTLD is preceded by a pre-clinical phase denoted by increased EBV DNA levels in the peripheral blood.…”