Human leukocyte antigens (HLA)-Cw as prognostic indicators in autologous transplantation for lymphoma

The human leukocyte antigens (HLA) function as a transplantation antigens a nd as markers in disease association. Disparity at the HLA A, B, Cw and DR loci in allogenic stem cell transplants results in an increased incidence o f graft-versus-host disease, graft rejection, and decreased survival. HLA c lass I loci A, B, and Cw also function as ligands for natural killer (NK) c ell receptors in an interaction that predominantly inhibits cytolysis of ta rget antigens. This HLA-NK cell inhibitory function is required for protect ion against auto-aggression, and is of unclear significance in other clinic al settings. Furthermore, the prevention of auto-aggression is HLA molecule specific as demonstrated by the association of specific HLA types with aut oimmune diseases. It is not known whether HLA molecules might serve as mark ers for outcome in autologous transplants. We investigated as association o f HLA class I molecules and early transplant outcome in a cohort of patient s who underwent autologous transplantation for the treatment of lymphoma. I n this retrospective study, HLA class I molecules were analysed to determin e whether they affect the transplant outcome. HLA typing was performed by m icrolymphocytotoxicity assays. Factors such as age, sex, disease type, lact ate dehydrogenase (LDH), cell dose, type of graft, and transfusion events w ere reviewed. Outcome was defined as death (or survival) at 6 months from t he date of transplant. HLA-Cw8 was significantly associated with poor outco me (odds ratio = 18 and 9.3, p = 0.01 and 0.02 in homozygous and all patien ts, respectively). The HLA-A and B locus molecules were not associated with outcome. Age, sex, elevated LDH, and cell dose were not associated with ou tcome. A blood progenitor cell dose of greater than 6 x 10(8) nucleated cel ls/kg was favorably associated with outcome. In the multivariate analysis o f HLAs and factors associated with outcome (p = 0.03) following autologous transplantation in lymphoma patients. The association of HLA-Cw molecules w ith outcome in this study group indicates a need for further investigation of HLA-mediated interactions that affect antitumor cytotoxicity, cytokine r elease, and regimen related toxicity.