HLA-DP?1 Asp84-Lys69 Antigen-binding Signature Predicts Event-free Survival In Childhood B-cell Precursor Acute Lymphoblastic Leukaemia: Results From The MRC UKALL XI Childhood ALL Trial.

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This article is from <a href="//archive.org/search.php?query=journaltitle%3A%28Blood%20Cancer%20Journal%29" rel="nofollow">Blood Cancer Journal</a>, <a href="//archive.org/search.php?query=journaltitle%3A%28Blood%20Cancer%20Journal%29%20AND%20volume%3A%282%29" rel="nofollow">volume 2</a>.<h2>Abstract</h2>We previously reported that children in the UKALL XI ALL trial with HLA-DP 1 and -DP 3 supertypes had significantly worse event-free survival (EFS) than children with other DP supertypes. As DP 1 and DP 3 share two of four key antigen-binding amino-acid polymorphisms (aspartic acid84–lysine69), we asked whether Asp84-Lys69 or Asp84 alone were independent prognostic indicators in childhood acute lymphoblastic leukemia (ALL). We analysed EFS in 798 UKALL XI patients, stratified by Asp84-Lys69 vs non-Asp84-Lys69, for a median follow-up of 12.5 years. Asp84-Lys69 was associated with a significantly worse EFS than non-Asp84-Lys69 (5-year EFS: Asp84-Lys69: 58.8% (95% CI (confidence of interval): 52.7–64.9%); non-Asp84-Lys69: 67.3% (63.4–71.2%); 2P=0.007). Post-relapse EFS was 10% less in Asp84-Lys69 than non-Asp84-Lys69 patients. EFS was significantly worse (P=0.03) and post-relapse EFS marginally worse (P=0.06) in patients with Asp84 compared with Gly84. These results suggest that Asp84-Lys69 predicted adverse EFS in the context of UKALL XI because of Asp84, and may have influenced post-relapse EFS. We speculate that this may be due to the recruitment of Asp84-Lys69-restricted regulatory T cells in the context of this regimen, leading to the re-emergence of residual disease. However, functional and molecular studies of the prognostic value of this and other HLA molecular signatures in other childhood ALL trials are needed.

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