T-CELL FUNCTION IN CHILDREN WITH ACUTE LYMPHOBLASTIC-LEUKEMIA

Modern intensive chemotherapy has dramatically improved the prognosis of acute lymphoblastic leukaemia (ALL) in children. However, once remission has been established, quality of life and even survival may be threatened by exacerbation of viral infections in the prolonged period of continuation therapy necessary to prevent relapse. Often the viruses involved in the most severe infections are from the herpesvirus and paramyxovirus groups, suggesting that patients suffer from a defect in the cellular immunity thought essential to control such cell-associated infections. This may result from a T cell defect and, in this study, T cell responsiveness of patients under therapy for leukaemia has been investigated. In vitro proliferative responses of peripheral blood leucocytes (PBL) to the T cell mitogen phytohaemagglutinin (PHA) were impaired in children with ALL before treatment and in the induction of remission. Impairment was attributable to reduced T cell numbers. the presence of inhibitors in the patient's serum and direct damage to lymphocytes. On achieving remission, proliferative responses to PHA of both CD4+ and CD8+ T cell subsets quickly returned to normal levels with the switch to continuation chemotherapy. Proliferative responses to Herpes simplex virus antigens were also apparently normal in the majority of patients tested in remission. Further investigations, however, have suggested a persisting defect in CD8+ lymphocyte function. Gamma interferon secretion by PHA-stimulated PBLs was severely reduced for children with ALL in remission when compared with control children of similar age. Further, cytotoxic T lymphocyte responses to allogeneic cells could only be induced in PBL isolated from two of 13 children in remission from ALL whilst all control children of similar age and adults produced anti-allogeneic responses.