The in vitro function of peripheral blood and bone marrow lymphocytes from 42 children with acute lymphocytic leukemia (ALL) in remission was evaluated before and after cessation of long-term combination immunosuppressive therapy. Lymphocyte function promptly recovers even after 3 yr of antineoplastic therapy, but the immunologic rebound varies, depending on whether the in vitro responses to phytohemagglutinin or various antigens are used as the index of lymphocyte function. The kinetics of immunologic rebound in three patients who relapsed following cessation of therapy did not differ from patients remaining in remission. In children off therapy there was a different distribution of antigen- and PHA-responsive lymphocytes between the peripheral blood and bone marrow compartments. This study provides further information at a cellular level on the immunologic rebound that follows cessation of long-term combination therapy. It emphasizes the need for controls in trials where immunotherapy is given after chemotherapy. Such controls are necessary before one can establish if the observed responses are due to adjuvants and/or tumor cells or are a reflection of the immunologic rebound that follows cessation of immunosuppressive therapy. The data also provide a baseline for future studies of immune impairment before leukemia relapse and the relationship between immunologic rebound and the duration of long-term leukemia-free survival.

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