Rituximab treatment for Epstein-Barr virus DNAemia after alternative-donor hematopoietic stem cell transplantation.
We report 55 patients undergoing an alternative-donor hematopoietic stem cell transplantation (HSCT) who developed Epstein-Barr virus (EBV) DNAemia, with >1000 EBV copies/10(5) peripheral blood mononuclear cells (PBMCs), and were treated with rituximab (375 mg/m(2)). The median patient age was 47 years (range, 20-65 years), and graft sources were mismatched family members (n = 4), unrelated donors (n = 46), and unrelated cord blood (n = 5). The conditioning regimen included antithymocyte globulin (ATG) in all patients. The median time to development of EBV DNAemia was day 27 post-HSCT (range, day 5 to day 242), with a median of 60 EBV copies/10(5) PBMCs (range, 1-5770 copies/10(5) PBMCs). The number of EBV copies was reduced to <1000/10(5) PBMCs on day +7 after initiation of rituximab therapy in 51% of the patients, on day +14 in 73% of the patients, and on +21 in 92% of the patients. Overall, 50 of 55 patients (91%) cleared EBV after one dose (n = 25) or more than one dose (n = 25) of rituximab. Factors predicting transplantation-related mortality (TRM) in multivariate analysis were a reduction to <1000 EBV copies/10(5) PBMCs by day +7 of treatment (relative risk [RR], 0.2; P = .01) and disease phase in remission (RR, 0.3; P = .05). TRM was 23% in the 40 patients with none or one of the negative predictors and 60% in the 15 patients with both negative predictors (P = .001). Of these latter 15 patients, 3 developed clinical posttransplantation lymphoproliferative disorder (PTLD). All 3 of these patients had a high EBV load on day +7 of rituximab therapy. This study confirms the effectiveness of rituximab in controlling EBV DNAemia in patients undergoing allogeneic HSCT. Patients with increasing EBV copies despite rituximab therapy are at high risk for EBV PTLD and may be considered for alternative therapies.
Division of Hematology and Bone Marrow Transplant, Ospedale San Martino, Genova, Italy. apbacigalupo@yahoo.com
Stefania
S
Coppoletta
Elisabetta
E
Tedone
Barbara
B
Galano
Monica
M
Soracco
Anna Maria
AM
Raiola
Teresa
T
Lamparelli
Francesca
F
Gualandi
Stefania
S
Bregante
Adalberto
A
Ibatici
Carmen
C
di Grazia
Alida
A
Dominietto
Riccardo
R
Varaldo
Barbara
B
Bruno
Francesco
F
Frassoni
Maria Teresa
MT
Van Lint
Andrea
A
Bacigalupo
D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000276:immunology*; D001782:Blood Donors; D004279:DNA, Viral / Q000097:blood; D054796:Drug Dosage Calculations; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000401:mortality / Q000821:virology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D004854:Herpesvirus 4, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000069283:Rituximab; D016019:Survival Analysis; D014180:Transplantation; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014766:Viremia / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D014775:Virus Activation / Q000187:drug effects
D058846:Antibodies, Monoclonal, Murine-Derived; D000961:Antilymphocyte Serum; D004279:DNA, Viral; D000069283:Rituximab