SUCCESSFUL TREATMENT OF HUMAN WALDENSTROM MACROGLOBULINEMIA WITH COMBINATION BIOLOGICAL AND CHEMOTHERAPY AGENTS

The immunomodulating effects and antitumor activity of two biological agents, bryostatin 1 (Bryo1) and alpha-interferon, were tested in vitr o and in vivo either alone or prior to chemotherapy agents, against a Waldenstrom's macroglobulinemia tumor line (WSU-WM). Bryo1 caused a de crease in the expression of CD10, CD19, IgM, Leu10, and CD22 and a tem porary growth inhibition as measured by cell cycle analysis. Alpha-int erferon did not show any major effects. In vivo, severe combined immun odeficient mice were used to test the activity of the agents against W SU-WM. Bryo1 (i.p.) was given either alone or sequentially with doxoru bicin (i.v.), vincristine (i.v.), melphalan (i.v.), and alpha-interfer on (i.v.). Bryo1 given 24 h before vincristine or melphalan resulted i n the highest tumor growth inhibition, tumor growth delay, and tumor c ell kill. Two of five mice receiving Bryo1/vincristine combination wer e free of tumors >200 days after treatment and were considered cured. In light of our findings, we recommend that Bryo1 be considered for cl inical investigation in human B-cell tumors and might best be given co mbined with other chemotherapy agents used in the treatment of that di sease. Whether Bryo1 is acting as a differentiating agent or as a dire ct anti-Waldenstrom's macroglobulinemia tumor agent, remains unclear.