HLA mismatch combinations associated with decreased risk of relapse: implications for the molecular mechanism.

Abstract:

:The finding that the risk of relapse in hematologic malignancy decreases after allogeneic hematopoietic stem cell transplantation (HSCT) has lead to the concept of a graft-versus-leukemia (GVL) effect. However, this beneficial effect is considered to be frequently offset by graft-versus-host disease (GVHD). Thus, improving HSCT outcomes by separating GVL from GVHD is a key clinical issue. This cohort study registered 4643 patients with hematologic malignancies who received transplants from unrelated donors. Six major human leukocyte antigen (HLA) loci were retrospectively genotyped. We identified 4 HLA-Cw and 6 HLA-DPB1 mismatch combinations responsible for a decreased risk of relapse; of these, 8 of 10 combinations were different from those responsible for severe acute GVHD, including all 6 of the HLA-DPB1 combinations. Pairs with these combinations of HLA-DPB1 were associated with a significantly better overall survival than were completely matched pairs. Moreover, several amino acid substitutions on specific positions responsible for a decreased risk of relapse were identified in HLA-Cw, but not in HLA-DPB1. These findings might be crucial to elucidating the mechanism of the decreased risk of relapse on the basis of HLA molecule. Donor selection made in consideration of these results might allow the separation of GVL from acute GVHD, especially in HLA-DPB1 mismatch combinations.

journal_name

Blood

journal_title

Blood

authors

Kawase T,Matsuo K,Kashiwase K,Inoko H,Saji H,Ogawa S,Kato S,Sasazuki T,Kodera Y,Morishima Y,Japan Marrow Donor Program.

doi

10.1182/blood-2008-08-171934

subject

Has Abstract

pub_date

2009-03-19 00:00:00

pages

2851-8

issue

12

eissn

0006-4971

issn

1528-0020

pii

blood-2008-08-171934

journal_volume

113

pub_type

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