TY - JOUR
T1 - Prognostic impact of Epstein-Barr virus serostatus in patients with nonmalignant hematological disorders undergoing allogeneic hematopoietic cell transplantation
T2 - The study of Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation
AU - Styczynski, Jan
AU - Tridello, Gloria
AU - Gil, Lidia
AU - Ljungman, Per
AU - Mikulska, Malgorzata
AU - Van Der Werf, Steffie
AU - Knelange, Nina Simone
AU - Averbuch, Diana
AU - Socié, Gerard
AU - Veelken, Hendrik
AU - Dalle, Jean Hugues
AU - Aljurf, Mahmoud
AU - Kupesiz, Alphan
AU - Bertrand, Yves
AU - Tbakhi, Abdelghani
AU - Afanasyev, Boris
AU - Lioure, Bruno
AU - Labussière-Wallet, Hélène
AU - Poiré, Xavier
AU - Maertens, Johan
AU - Petersen, Eefke
AU - Chevallier, Patrice
AU - Milpied, Noel
AU - Snowden, John A.
AU - Yakoub-Agha, Ibrahim
AU - Cornelissen, Jan
AU - Schaap, Nicolaas
AU - Dufour, Carlo
AU - De Latour, Regis Peffault
AU - Lankester, Arjan
AU - Cesaro, Simone
PY - 2020/6/1
Y1 - 2020/6/1
N2 - In patients with acute leukemia, lymphoma and chronic malignancies, donor and/or recipient Epstein-Barr virus (EBV) seropositive status increases the risk of development of chronic graft-versus-host disease (cGVHD) after allo-hematopoietic cell transplantation (allo-HCT), while it has no influence on other transplant outcomes. No data are available on the impact of EBV serostatus on transplant outcomes in patients with nonmalignant hematological disorders. 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); nonrelapse mortality (NRM); acute graft-versus-host disease (aGVHD); cGVHD) in patients with nonmalignant hematological disorders undergoing allo-HCT. A total of 2,355 allo-HCTs performed between 1997 and 2016 for acquired bone marrow failure or hemoglobinopathies were included in this retrospective Registry megafile Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation (IDWP-EBMT) study. Demographics: The median age of recipient was 17.7 years (range: 0-77), and 50.8% were children. 79.0% of recipients and 75.4% of donors were EBV-seropositive. 67.8% had HCT from a matched family donor, 4.6% from a mismatched family donor, and 27.6% from an unrelated donor (UD). T-cell depletion was performed in vivo and ex vivo in 82.2% and 6.6% of patients, respectively. Conditioning regimen was myeloablative in 63.7% and reduced intensity conditioning (RIC) in 36.3% of patients. The median follow-up was 4.7 years. Transplant outcomes: EBV-seropositive recipients in comparison with EBV-seronegative recipients had lower OS (85.4% vs. 88.4%, p = 0.035) and higher NRM (10.0% vs. 6.4%, p = 0.018). No other significant differences were found for: RI, RFS, and aGVHD or cGVHD with respect to EBV pretransplant serostatus donor and/or recipient. Multivariate analysis: A trend toward higher risk of development of cGVHD (HR = 1.31; p = 0.081) and better survival (HR = 0.78; p = 0.087) in allo-HCT from EBV-seropositive donors was found. Allo-HCT in EBV-seropositive recipients had a trend toward lower risk of development of cGVHD (HR = 0.75; p = 0.065). When four subgroups (R-/D-, R-/D+, R+/D-, R+/D+ EBV serology) were analyzed, the EBV serostatus had no significant impact on OS, RFS, RI, NRM and development of aGVHD or cGVHD. Allo-HCT from EBV-seropositive versus EBV-seronegative donors are at 31% higher risk of cGVHD in patients with nonmalignant hematological disorders undergoing allo-HCT; however this difference is nonsignificant in multivariate analysis.
AB - In patients with acute leukemia, lymphoma and chronic malignancies, donor and/or recipient Epstein-Barr virus (EBV) seropositive status increases the risk of development of chronic graft-versus-host disease (cGVHD) after allo-hematopoietic cell transplantation (allo-HCT), while it has no influence on other transplant outcomes. No data are available on the impact of EBV serostatus on transplant outcomes in patients with nonmalignant hematological disorders. 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); nonrelapse mortality (NRM); acute graft-versus-host disease (aGVHD); cGVHD) in patients with nonmalignant hematological disorders undergoing allo-HCT. A total of 2,355 allo-HCTs performed between 1997 and 2016 for acquired bone marrow failure or hemoglobinopathies were included in this retrospective Registry megafile Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation (IDWP-EBMT) study. Demographics: The median age of recipient was 17.7 years (range: 0-77), and 50.8% were children. 79.0% of recipients and 75.4% of donors were EBV-seropositive. 67.8% had HCT from a matched family donor, 4.6% from a mismatched family donor, and 27.6% from an unrelated donor (UD). T-cell depletion was performed in vivo and ex vivo in 82.2% and 6.6% of patients, respectively. Conditioning regimen was myeloablative in 63.7% and reduced intensity conditioning (RIC) in 36.3% of patients. The median follow-up was 4.7 years. Transplant outcomes: EBV-seropositive recipients in comparison with EBV-seronegative recipients had lower OS (85.4% vs. 88.4%, p = 0.035) and higher NRM (10.0% vs. 6.4%, p = 0.018). No other significant differences were found for: RI, RFS, and aGVHD or cGVHD with respect to EBV pretransplant serostatus donor and/or recipient. Multivariate analysis: A trend toward higher risk of development of cGVHD (HR = 1.31; p = 0.081) and better survival (HR = 0.78; p = 0.087) in allo-HCT from EBV-seropositive donors was found. Allo-HCT in EBV-seropositive recipients had a trend toward lower risk of development of cGVHD (HR = 0.75; p = 0.065). When four subgroups (R-/D-, R-/D+, R+/D-, R+/D+ EBV serology) were analyzed, the EBV serostatus had no significant impact on OS, RFS, RI, NRM and development of aGVHD or cGVHD. Allo-HCT from EBV-seropositive versus EBV-seronegative donors are at 31% higher risk of cGVHD in patients with nonmalignant hematological disorders undergoing allo-HCT; however this difference is nonsignificant in multivariate analysis.
KW - Epstein-Barr virus
KW - graft-versus-host disease
KW - hematopoietic cell transplant
KW - overall survival
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U2 - 10.2478/ahp-2020-0015
DO - 10.2478/ahp-2020-0015
M3 - Article
AN - SCOPUS:85087571975
VL - 51
SP - 73
EP - 80
JO - Acta Haematologica Polonica
JF - Acta Haematologica Polonica
SN - 0001-5814
IS - 2
ER -