title: Impact of HLA A2 and cytomegalovirus serostatus on outcomes in patients with leukemia following matched-sibling myeloablative allogeneic hematopoietic cell transplantation.
abstract: OBJECTIVE
  Donor cytomegalovirus seropositivity was reported to improve leukemia outcomes in HLA-A2 identical hematopoietic cell transplant (HCT) recipients, due to a possible cross-reactivity of donor HLA-A2-restricted CMV-specific T cells with minor histocompatibility (H) antigen of recipient cells. This study analyzed the role of donor CMV serostatus and HLA-A2 status on leukemia outcomes in a large population of HLA-identical HCT recipients.
  
  
  METHODS
  Leukemia patients transplanted between 1992 and 2003 at the Fred Hutchinson Cancer Research Center were categorized as standard risk [leukemia first remission, chronic myeloid leukemia in chronic phase (CML-CP)] and high risk (advanced disease) patients. Time-to-event analysis was used to evaluate the risk of relapse and death associated with HLA-A2 status and donor CMV serostatus.
  
  
  RESULTS
  In standard risk patients, acute leukemia (p<0.001) and sex mismatch (female to male, p=0.004)) independently increased the risk of death, while acute leukemia increased the risk of relapse (p<0.001). In high risk patients acute leukemia (p=0.01), recipient age > or = 40 (p=0.005) and herpes simplex virus (HSV) seropositivity (p<0.001) significantly increased the risk death; HSV seropositivity (p=0.006) increased the risk of relapse. Donor CMV serostatus had no significant effect on mortality or relapse in any HLA group.
  
  
  CONCLUSIONS
  This epidemiological study did not confirm the previously reported effect of donor CMV serostatus on the outcomes of leukemia in HLA-A2-identical HCT recipients. Addressing the question of cross-reactivity of HLA-A2-restricted CMV-specific T cells with minor H antigens in a clinical study would require knowledge of the patient's minor H antigen genotype. However, because of the unbalanced distribution of HLA-A2-restricted minor H antigens in the population and their incomplete identification, this question might be more appropriately evaluated in in vitro experiments than in a clinical study.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Veronique
authors.initials: V
authors.lastname: Erard
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Guthrie
authors.forename: Stanley
authors.initials: S
authors.lastname: Riddell
authors.forename: Michael
authors.initials: M
authors.lastname: Boeckh
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000235:genetics / Q000378:metabolism; D005260:Female; D015789:HLA-A2 Antigen / Q000097:blood* / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation / Q000639:trends; D006650:Histocompatibility Testing / Q000639:trends; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000097:blood* / Q000453:epidemiology / Q000235:genetics / Q000601:surgery; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D035781:Siblings; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000639:trends
chemical_list: D015789:HLA-A2 Antigen; D019653:Myeloablative Agonists