title: Impact of HLA class I and class II DNA high-resolution HLA typing on clinical outcome in adult unrelated stem cell transplantation after in vivo T-cell depletion with alemtuzumab.
abstract: Survival after volunteer unrelated donor (VUD) stem cell transplantation (SCT) is influenced by matching for human leucocyte antigens (HLA). We analysed the effects of serological and molecular typing at HLA-A, -B, -C and -DRB1 in 100 patient/VUD pairs from a single transplant centre. Patients received SCT for good risk [chronic myeloid leukaemia in first chronic phase (CML-CP1), n=55] or poor risk (n=45) diseases after myeloablative conditioning and T-cell depletion with alemtuzumab. By serological typing, 70 pairs were fully matched, whereas molecular typing revealed 10 pairs with additional mismatches. The day 100 transplant related mortality was 15%. Acute graft versus host disease (GvHD) grades III-IV occurred in 11%, whilst extensive chronic GvHD in 13% of evaluable patients. There was no statistical difference in GvHD rates between patients who received grafts from fully matched or from mismatched donors. In univariate analysis the disease risk group and CMV seronegativity of recipient and donor were the only significant predictors for survival, with 3-year survival probabilities of 71.2% for CML-CP1 and 28% for poor risk diseases. In the poor risk group, HLA mismatches had a negative impact on survival (p=0.003) and progression free survival (p=0.009) contrary to CML-CP1 patients, in whom HLA mismatches at molecular or serological level did not have any impact.
authors.affiliation: Department of Haematology, Hammersmith Hospital, Hammersmith Hospital NHS, Imperial College School of Medicine, London, United Kingdom. jolanta@tjdengler.info
authors.forename: Jolanta B
authors.initials: JB
authors.lastname: Perz
authors.forename: Richard
authors.initials: R
authors.lastname: Szydlo
authors.forename: Ruhena
authors.initials: R
authors.lastname: Sergeant
authors.forename: Jaime
authors.initials: J
authors.lastname: Sanz
authors.forename: Derville
authors.initials: D
authors.lastname: O'Shea
authors.forename: Thahmina
authors.initials: T
authors.lastname: Khan
authors.forename: Nick
authors.initials: N
authors.lastname: Davey
authors.forename: Sandra
authors.initials: S
authors.lastname: Loaiza
authors.forename: John
authors.initials: J
authors.lastname: Davis
authors.forename: Jane F
authors.initials: JF
authors.lastname: Apperley
authors.forename: Eduardo
authors.initials: E
authors.lastname: Olavarria
mesh_terms: D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006085:Graft Survival / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation / Q000379:methods*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D000074323:Alemtuzumab