Successful treatment of human Waldenström's 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 vitro and in vivo either alone or prior to chemotherapy agents, against a Waldenström's macroglobulinemia tumor line (WSU-WM). Bryol caused a decrease in the expression of CD10, CD19, IgM, Leu10, and CD22 and a temporary growth inhibition as measured by cell cycle analysis. alpha-Interferon did not show any major effects. In vivo, severe combined immunodeficient mice were used to test the activity of the agents against WSU-WM. Bryo1 (i.p.) was given either alone or sequentially with doxorubicin (i.v.), vincristine (i.v.), melphalan (i.v.), and alpha-interferon (i.v.). Bryo1 given 24 h before vincristine or melphalan resulted in the highest tumor growth inhibition, tumor growth delay, and tumor cell kill. Two of five mice receiving Bryo1/vincristine combination were free of tumors > 200 days after treatment and were considered cured. In light of our findings, we recommend that Bryo1 be considered for clinical investigation in human B-cell tumors and might best be given combined with other chemotherapy agents used in the treatment of that disease. Whether Bryo1 is acting as a differentiating agent or as a direct anti-Waldenström's macroglobulinemia tumor agent, remains unclear.
Mohammad
R M
RM
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48202.
al-Katib
A
A
Pettit
G R
GR
Sensenbrenner
L L
LL
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers; D054713:Bryostatins; D002453:Cell Cycle / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D007783:Lactones / Q000008:administration & dosage; D018942:Macrolides; D008558:Melphalan / Q000008:administration & dosage; D051379:Mice; D016513:Mice, SCID; D014750:Vincristine / Q000008:administration & dosage; D008258:Waldenstrom Macroglobulinemia / Q000473:pathology / Q000628:therapy*
D015415:Biomarkers; D054713:Bryostatins; D016898:Interferon-alpha; D007783:Lactones; D018942:Macrolides; C046785:bryostatin 1; D014750:Vincristine; D008558:Melphalan