title: Persisting posttransplantation cytomegalovirus antigenemia correlates with poor lymphocyte proliferation to cytomegalovirus antigen and predicts for increased late relapse and treatment failure.
abstract: Numerous clinical studies link cytomegalovirus (CMV) infection with incomplete posttransplantation T-cell recovery. We hypothesized that the inability of transplant recipients to handle CMV reactivation might correlate with a defective graft-versus-leukemia response and increased posttransplantation morbidity. Between May 1995 and August 2001, 82 patients who were CMV seropositive and survived the first 100 days after transplantation were identified for a day 100 landmark analysis of the effect of CMV reactivation patterns on eventual transplantation outcome. All patients underwent a myeloablative HLA-identical sibling donor T cell-depleted stem cell transplantation with scheduled donor T-cell add-back on day 45. Median follow-up was 1032 days. Forty-two patients who had either no reactivation or only 1 positive test with quick clearance were designated as a CMV immune competent group. Forty patients designated as CMV immune deficient (ID) had at least 2 positive tests. Apart from younger age (33 versus 38 years; P =.05) in the ID group, the 2 groups were balanced for clinical characteristics. In multivariate analysis, ID patients had a significantly higher incidence of leukemia relapse (58% versus 21%; P =.03) and worse disease-free survival (31% versus 66%; P =.04). There was no significant difference in week 1 to 14 posttransplantation lymphocyte counts between the 2 groups. In 67 patients tested 3 to 6 months after transplantation, a proliferative response to CMV antigen (stimulation index > or =2) occurred in 27 of 36 immune competent patients compared with 15 of 31 ID patients (P =.006). These results show that recurrent CMV reactivation in the first 100 days after transplantation predicts for reduced disease-free survival and increased leukemic relapse beyond 100 days and correlates with inferior proliferative responses to CMV. The higher relapse rate may reflect poor immune reconstitution in ID patients or an adverse effect of prolonged antiviral treatment.
authors.affiliation: Stem Cell Allogenetic Transplant Unit, Hematology Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892, USA.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Nakamura
authors.forename: Minoo
authors.initials: M
authors.lastname: Battiwalla
authors.forename: Scott
authors.initials: S
authors.lastname: Solomon
authors.forename: Dean
authors.initials: D
authors.lastname: Follmann
authors.forename: Sakti
authors.initials: S
authors.lastname: Chakrabarti
authors.forename: Karoll
authors.initials: K
authors.lastname: Cortez
authors.forename: Nancy
authors.initials: N
authors.lastname: Hensel
authors.forename: Richard
authors.initials: R
authors.lastname: Childs
authors.forename: A John
authors.initials: AJ
authors.lastname: Barrett
mesh_terms: D000293:Adolescent; D000328:Adult; D000956:Antigens, Viral / Q000097:blood* / Q000276:immunology; D002648:Child; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000276:immunology; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007938:Leukemia / Q000628:therapy; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D014184:Transplantation, Homologous; D017211:Treatment Failure; D014775:Virus Activation / Q000276:immunology
chemical_list: D000956:Antigens, Viral