ABSTRACT
Five of 39 (13%) women treated with adjuvant combination chemotherapy plus levamisole immunotherapy after mastectomy for Stage II or III breast cancer developed levamisole-induced granulocytopenia. This complication occurred in each of the women between six and ten weeks after the completion of six months of combination chemoimmunotherapy when they were taking levamisole alone. Although none of the patients had an HLA B-27 locus and leukoagglutinins could not be demonstrated, complement-dependent, IgM mediated, peripheral destruction of granulocytes was documented using a microgranulocytotoxicity assay. In addition, a factor(s) present in serum from patients developing levamisole-induced granulocytopenia caused suppression of bone marrow granulocyte progenitor cells (CFU-C). The possible relationships between levamisole-induced peripheral granulocyte destruction and bone marrow CFU-C suppression are discussed.
Subject(s)
Agranulocytosis/etiology , Breast Neoplasms/complications , Levamisole/adverse effects , Acute Disease , Adult , Aged , Agranulocytosis/complications , B-Lymphocytes/immunology , Breast Neoplasms/drug therapy , Colony-Forming Units Assay , Concanavalin A/pharmacology , Cyclophosphamide/therapeutic use , Cytotoxicity, Immunologic , Doxorubicin/therapeutic use , Drug Therapy, Combination , Female , Fluorouracil/therapeutic use , Hemagglutination Tests , Humans , Levamisole/therapeutic use , Methotrexate/therapeutic use , Middle Aged , Phytohemagglutinins/pharmacology , T-Lymphocytes/immunologyABSTRACT
We devised a method to enhance delivery of vinblastine to macrophages, the cells believed to be responsible for platelet destruction in idiopathic thrombocytopenic purpura. Our strategy was based on the ability of platelets to bind vinca alkaloids such as vinblastine. Platelets were incubated with an excess of vinblastine, concentrated and then, after excess alkaloid had been removed, given to 11 patients with idiopathic thrombocytopenia refractory to other treatment (including intravenous injections of vinca alkaloids). Platelet antibodies in the patients' plasma led to ingestion of the vinca-laden platelets by macrophages. There were six complete remissions, three partial remissions and two failures. Side effects in a few patients, reversible but annoying, were minimized as technics were refined. We conclude that in patients with idiopathic thrombocytopenia refractory to all other measures, including the use of vinca alkaloids, platelet-vinca complex may be effective.
