title: Relationship between HLA-DP supertype and survival in childhood acute lymphoblastic leukaemia: evidence for selective loss of immunological control of residual disease?
abstract: 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.
authors.affiliation: Cancer Immunogenetics, School of Cancer Sciences, University of Manchester, Manchester, UK. gmtaylor@manchester.ac.uk
authors.forename: G Malcolm
authors.initials: GM
authors.lastname: Taylor
authors.forename: Sue
authors.initials: S
authors.lastname: Richards
authors.forename: Rachel
authors.initials: R
authors.lastname: Wade
authors.forename: Adiba
authors.initials: A
authors.lastname: Hussain
authors.forename: Jill
authors.initials: J
authors.lastname: Simpson
authors.forename: Frank
authors.initials: F
authors.lastname: Hill
authors.forename: Chris
authors.initials: C
authors.lastname: Mitchell
authors.forename: Tim
authors.initials: T
authors.lastname: Eden
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000235:genetics*; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006682:HLA-DP Antigens / Q000235:genetics*; D059868:HLA-DP beta-Chains; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D018365:Neoplasm, Residual / Q000235:genetics* / Q000276:immunology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C054111:HLA-DPw1 antigen; C083176:HLA-DPw2 antigen; C055961:HLA-DPw3 antigen; C056284:HLA-DPw4 antigen; D007166:Immunosuppressive Agents; D008727:Methotrexate