HLA-DPβ1 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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AbstractWe 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.
CitationHLA-DPβ1 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. 2012, 2 (7): Blood Cancer J
JournalBlood Cancer Journal
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- Authors: Taylor GM, Richards S, Wade R, Hussain A, Simpson J, Hill F, Mitchell C, Eden T, UKCCS and CCLG Investigators.
- Issue date: 2009 Apr
- Successful treatment without cranial radiotherapy of children receiving intensified chemotherapy for acute lymphoblastic leukaemia: results of the risk-stratified randomized central nervous system treatment trial MRC UKALL XI (ISRC TN 16757172).
- Authors: Hill FG, Richards S, Gibson B, Hann I, Lilleyman J, Kinsey S, Mitchell C, Harrison CJ, Eden OB, UK Medical Research Council Working Party on Childhood Leukaemia.
- Issue date: 2004 Jan
- Benefit of intensified treatment for all children with acute lymphoblastic leukaemia: results from MRC UKALL XI and MRC ALL97 randomised trials. UK Medical Research Council's Working Party on Childhood Leukaemia.
- Authors: Hann I, Vora A, Richards S, Hill F, Gibson B, Lilleyman J, Kinsey S, Mitchell C, Eden OB
- Issue date: 2000 Mar
- Comparison of allogeneic transplant versus chemotherapy for relapsed childhood acute lymphoblastic leukaemia in the MRC UKALL R1 trial. MRC Childhood Leukaemia Working Party.
- Authors: Harrison G, Richards S, Lawson S, Darbyshire P, Pinkerton R, Stevens R, Oakhill A, Eden OB
- Issue date: 2000 Aug
- Failure of a new protocol to improve treatment results in paediatric lymphoblastic leukaemia: lessons from the UK Medical Research Council trials UKALL X and UKALL XI.
- Authors: Chessells JM, Harrison G, Richards SM, Gibson BE, Bailey CC, Hill FG, Hann IM, Medical Research Council Working Party On Childhood Leukaemia.
- Issue date: 2002 Aug