Impact of HLA A2 and cytomegalovirus serostatus on outcomes in patients with leukemia following matched-sibling myeloablative allogeneic hematopoietic cell transplantation.

Details

Serval ID
serval:BIB_ACD66A17C547
Type
Article: article from journal or magazin.
Publication sub-type
Case report (case report): feedback on an observation with a short commentary.
Collection
Publications
Institution
Title
Impact of HLA A2 and cytomegalovirus serostatus on outcomes in patients with leukemia following matched-sibling myeloablative allogeneic hematopoietic cell transplantation.
Journal
Haematologica
Author(s)
Erard Véronique, Guthrie Katherine A., Riddell Stanley, Boeckh Michael
ISSN
1592-8721[electronic]
Publication state
Published
Issued date
2006
Volume
91
Number
10
Pages
1377-1383
Language
english
Notes
Publication types: Comparative Study
Abstract
BACKGROUND AND OBJECTIVES: 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. DESIGN AND 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. INTERPRETATION AND CONCLUSION: 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.
Keywords
Adolescent, Adult, Child, Child, Preschool, Cytomegalovirus/genetics, Cytomegalovirus/metabolism, Female, HLA-A2 Antigen/blood, HLA-A2 Antigen/genetics, Hematopoietic Stem Cell Transplantation/trends, Histocompatibility Testing/trends, Humans, Infant, Leukemia/blood, Leukemia/epidemiology, Male, Middle Aged, Myeloablative Agonists/therapeutic use, Siblings, Tissue Donors, Transplantation Conditioning/trends
Pubmed
Web of science
Create date
02/02/2010 17:21
Last modification date
20/08/2019 16:16
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