Donor EBV-Positive Serostatus Increases the Risk of Chronic GVHD in Patients with Myeloid and Lymphoid Malignancies Other Than Acute Leukemia: Infectious Diseases Working Party EBMT Study

Abstract

BACKGROUND: In patients with acute leukemia (AL), donor EBV (Epstein-Barr Virus) seropositive status significantly increases the risk of development of acute and chronic GVHD after allo-HSCT, while it has no influence on other transplant outcomes (OS, RFS, RI, NRM) (Styczynski et al , J Clin Oncol, 2016). No data are available on the impact of EBV serostatus on transplant outcomes in patients with other hematological malignancies.OBJECTIVE: We analyzed the influence of the recipient's (R) and donor's (D) EBV serostatus on transplant outcomes (overall survival, OS; relapse-free survival, RFS; relapse incidence, RI; non-relapse mortality, NRM; acute graft-versus-host disease, aGVHD; chronic graft-versus-host disease, cGVHD) in patients with myeloid and lymphoid malignancies other than AL undergoing allo-HSCT.PATIENTS AND METHODS: 12,931 allo-HSCTs performed between 1997 and 2016 for myeloid (58.1%) or lymphoid malignancies (41.9%), other than AL, with PB (76%) or BM±PB (24%) as a stem cell source were included in this retrospective Registry megafile IDWP EBMT study.RESULTS:DEMOGRAPHICS : 48% had HSCT from a matched family donor, 4.2% from a mismatched family donor, and 47.8 from an unrelated donor. T-cell depletion was performed in vivo in 58.4%, and ex vivo in 7.9% patients. Conditioning regimen was myeloablative in 41.3%, RIC in 58.7%. Median follow-up was 4.7 years. TRANSPLANT OUTCOMES : EBV-seropositive patients receiving grafts from EBV-seropositive donors (EBV R+/D+ transplants) had worse transplant outcomes in comparison to EBV-seronegative patients receiving grafts from EBV-seronegative donors (EBV R-/D-): lower OS (59.6% vs 65.9%), lower RFS (51.1% vs 57.5%), higher incidence of chronic GVHD (49.5% vs 41.8%), and higher incidence of de novo chronic GVHD (30.5% vs 24.0%). No significant differences were found for: RI, NRM, and acute GVHD (Table 1). MULTIVARIATE ANALYSIS : Allo-HSCT from EBV-seropositive donors had higher risk of development of cGVHD (HR=1.13; p=0.0096). When 4 subgroups (R-/D-, R-/D+, R+/D-, R+/D+ EBV serology) were analyzed, the risk of cGVHD was higher for EBV R-/D+ (HR=1.22; p=0.0395), R+/D- (HR=1.21; p=0.0375), and for R+/D+ (HR=1.28; p=0.0013) when compared to R-/D- transplants. On the other hand, R/D EBV serostatus had no significant impact on OS, RFS, RI, NRM and development of acute GVHD. Finally, since the R-/D- combination patients were more likely to be children than R+/D+, this could explain the effect in univariate analysis on OS and RFS while the chronic GVHD effect was independent of age.CONCLUSIONS: Allo-HSCT from EBV-seropositive donors are at 13% higher risk of chronic GVHD in patients with myeloid and lymphoid malignancies other than AL. [Display omitted] DisclosuresPetersen:Sanofi: Membership on an entity's Board of Directors or advisory committees. Leblond:SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees; GILEAD: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; JANSSEN: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ABBVIE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ROCHE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria; NOVARTIS: Honoraria, Membership on an entity's Board of Directors or advisory committees. Michallet:medac GmbH, Wedel, Germany: Honoraria, Other: Travel grants. Kröger:Janssen Global Services, LLC: Speakers Bureau; Amgen Inc.: Speakers Bureau; Novartis AG: Research Funding; RIEMSER Pharma: Research Funding; Neovii Pharmaceuticals AG: Speakers Bureau; Novartis AG: Speakers Bureau; Sanofi: Speakers Bureau.