Identification of immune evasion strategies of pediatric pre-B acute lymphoblastic leukemia after bone marrow transplantation

Abstract

8555 Background: Bone marrow transplantation (BMT) is the only curative option for refractory/relapsed pediatric acute lymphoblastic leukemia (ALL). However, post-BMT relapse remains an important cause of transplantation failure. Immune mechanisms play a critical role in the anti-leukemic efficacy of BMT, suggesting that mechanisms allowing leukemic blasts to evade immune responses are important in leukemia relapse. An improved understanding of the processes underlying post-BMT ALL relapse is required. Methods: In this study several methods were utilised to assess and compare the allogeneic and autologous T cell responses induced by pediatric pre-B ALL cells which had been obtained at various time points from a pediatric patient with pre-B ALL who relapsed following allogeneic BMT. All patient samples were also extensively phenotyped in order to determine the degree of co-stimulatory molecule expression on the leukemic blasts. Results: We observed a dramatic loss of T cell stimulatory capacity by later relapse samples. Also, the autologous anti-leukemic T cell response demonstrated a Th2 shift compared to the Th1 allogeneic response. These immune stimulatory changes induced by ALL cells at relapse were associated with changes in expression of MHC and costimulatory molecules. HLA-ABC expression was increased on all relapse samples. HLA-DR expression was substantially reduced in those relapse samples obtained following immunosuppression cessation. Expression of the costimulatory molecule CD137L was decreased on post-BMT relapse samples whereas B7-H1 expression was increased. Conclusions: These results reveal mechanisms involved in pre-B ALL relapse, and suggest strategies to prevent evasion of the graft-versus-leukemia effect by ALL cells. No significant financial relationships to disclose.