Relationship between HLA-DP supertype and survival in childhood acute lymphoblastic leukaemia: evidence for selective loss of immunological control of residual disease?

TY - JOUR

T1 - Relationship between HLA-DP supertype and survival in childhood acute lymphoblastic leukaemia: evidence for selective loss of immunological control of residual disease?

AU - Taylor, G. Malcolm

AU - Richards, Sue

AU - Wade, Rachel

AU - Hussain, Adiba

AU - Simpson, Jill

AU - Hill, Frank

AU - Mitchell, Chris

AU - Eden, Tim

AU - UKCCS CCLG Investigators

PY - 2009/4

Y1 - 2009/4

N2 - We recently reported that two of six HLA-DP supertypes (DP1-4, 6, 8) were associated with susceptibility (DP2) and resistance (DP1) to childhood acute lymphoblastic leukaemia (ALL). To determine whether DP supertypes are associated with childhood ALL prognosis, we compared treatment outcomes in a cohort (n = 798) of DPB1-typed ALL cases in the UK Medical Research Council UKALL XI trial. No differences in clinical characteristics and outcome between DPB1-typed and untyped (n = 1292) cases suggest no selection bias. Event-free survival (EFS) rates in patients with DP1 and DP3 supertypes were significantly worse than in patients with DP2, DP4, DP6 and DP8 [10-year EFS: 55%; 95% confidence interval (CI) = 49-61%; compared with 64% (61-68%), P = 0.006]. Ten-year EFS in DP1/DP3 heterozygous patients [30% (2-58%)] was significantly worse than in patients with DP1, DP3 or neither allele [56% (50-62%); P = 0.02]. Lack of evidence that DP1 or DP3 are associated with known prognostic factors leads us to suggest that these two supertypes exert an independent effect on prognosis. This may involve abrogation of DP1/3-restricted T-cell control of residual disease due to selective effects of chemotherapy. Further studies of HLA supertypes in relation to outcome in recent childhood ALL trials may resolve this question.

AB - We recently reported that two of six HLA-DP supertypes (DP1-4, 6, 8) were associated with susceptibility (DP2) and resistance (DP1) to childhood acute lymphoblastic leukaemia (ALL). To determine whether DP supertypes are associated with childhood ALL prognosis, we compared treatment outcomes in a cohort (n = 798) of DPB1-typed ALL cases in the UK Medical Research Council UKALL XI trial. No differences in clinical characteristics and outcome between DPB1-typed and untyped (n = 1292) cases suggest no selection bias. Event-free survival (EFS) rates in patients with DP1 and DP3 supertypes were significantly worse than in patients with DP2, DP4, DP6 and DP8 [10-year EFS: 55%; 95% confidence interval (CI) = 49-61%; compared with 64% (61-68%), P = 0.006]. Ten-year EFS in DP1/DP3 heterozygous patients [30% (2-58%)] was significantly worse than in patients with DP1, DP3 or neither allele [56% (50-62%); P = 0.02]. Lack of evidence that DP1 or DP3 are associated with known prognostic factors leads us to suggest that these two supertypes exert an independent effect on prognosis. This may involve abrogation of DP1/3-restricted T-cell control of residual disease due to selective effects of chemotherapy. Further studies of HLA supertypes in relation to outcome in recent childhood ALL trials may resolve this question.

KW - paediatric

KW - acute lymphoblastic leukaemia

KW - HLA-DPB1

KW - DP supertypes

KW - prognosis

KW - CHILDRENS CANCER GROUP

KW - TUMOR-NECROSIS-FACTOR

KW - MRC UKALL XI

KW - PEPTIDE-BINDING

KW - RANDOMIZED-TRIALS

KW - DENDRITIC CELLS

KW - IN-VITRO

KW - GLUCOCORTICOIDS

KW - DEXAMETHASONE

KW - THERAPY

UR - http://www.scopus.com/inward/record.url?scp=61849174824&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2141.2008.07571.x

DO - 10.1111/j.1365-2141.2008.07571.x

M3 - Article

SN - 0007-1048

VL - 145

SP - 87

EP - 95

JO - British Journal of Haematology

JF - British Journal of Haematology

IS - 1

ER -