These studies are designed to define further and more rationally the biological heterogeneity of hematologic malignancies in children - acute lymphoblastic leukemia (ALL), Hodgkin's disease (HD), and non-Hodgkin's lymphoma (NHL). The emphasis will be on extensive multidisciplinary laboratory studies designed to determine the derivation of malignant cells, their immunobiologic, biochemical, and cytogenetic characteristics, and the cellular interactions that determine or influence host response to disease and prognosis. Using the extensive laboratory resources of the Center, we will examine in detail in ALL: 1) steroid receptors and proteolytic enzymes in leukemia; 2) T-cell differentiation and function in ALL; 3) B-cell regulation and resistance in ALL with particular references to leukemia-induced immune deficiencys 4) cell cytofluorometric studies of aneuploidy and cytogenetics in ALL; 5) regulation of hematopoiesis in AL; and in lymphoma: 1) tissue culture of HD cells; 2) immunoregulation and generation of antibody; and 3) prostaglandins. The relationship between well-established clinical prognostic factors, immunological cell surface markers using heterologous and monoclonal antibody techniques and these additional biological characteristics will be the major thrusts of the laboratory studies which will be performed in concert with controlled clinical Phase III trials in collaboration with Children's Cancer Study Group and institutional pediatric Phase I/II developmental chemotherapy trials of new agents. Laboratory studies will emphasize pharmacokinetics and classical clinical pharmacologic evaluation of new agents under clinical investigation.
