Immunologic Rebound After Cessation of Long-term Chemotherapy in Acute Leukemia

Abstract

Abstract The aim of this study was to determine the kinetics of repopulation of blood and bone marrow lymphocytes, immunoglobulin synthesis, and antibody production after stopping long-term combination chemotherapy in children with acute lymphocytic leukemia (ALL) in continuous remission for 2½-3 yr. The phase of recovery after immunosuppressive drugs were discontinued was characterized by a rise of lymphocytes and increased immunoglobulin and antibody production, and it was dependent on the age of the patients at the beginning of treatment. Thus, after the drugs were stopped, blood and bone marrow lymphocytes and serum IgG and IgM increased significantly in the group of patients younger than 5 yr but not in the older group. Lymphocytosis was more pronounced and earlier in bone marrow, suggesting an initial expansion of this cell compartment. After the drugs were discontinued one-fourth of these patients had a rise in antibody to the Hong Kong influenza virus without evidence of reexposure to the same antigen. Although the mechanisms of this age-dependent immunologic rebound are uncertain, we postulate that the number of long-lived, drug-resistant, memory lymphocytes increases in peripheral blood as a function of age and antigenic stimulation. Practical implications derived from this study are: an increase of bone marrow lymphocytes above 40% in children with ALL in whom chemotherapy has been stopped does not indicate relapse but may be a manifestation of immunologic recovery; and a rise in antibody titers after cessation of immunosuppressive drugs may reflect immunologic rebound to an "old" antigen and not necessarily be secondary to an active infectious process.