Mechanisms of levamisole‐induced granulocytopenia in breast cancer patients

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.

Levamisole in the Treatment of Advanced Breast Cancer: A ten-year follow-up of a Randomized Study

“…In favourably reacting cases levamisole treatment has been found to induce a serum factor which itself causes immunostimulation in other individuals and in vitro (24). A serum factor which causes the degradation of granulocytes has also been found in patients developing agranulocytosis (25). The studies of levamisole in stage IV breast cancer by the SWOG (9) and SEG (8) gave different results.…”

Clinicopathologic Features of Agranulocytosis in the Setting of Levamisole-Tainted Cocaine

“…These findings are directly analogous to those of prior investigators who detected granulocyte-agglutinating or granulocytotoxic antibodies in 25% to 100% of levamisoleassociated agranulocytosis. 9,16,[19][20][21][22][23] The exact mechanism by which such antibodies are formed is unclear, although the dispensability of the presence of the drug for antigen binding may suggest cross-reactivity rather than a hapten-mediated process.…”

Reversible thrombocytopenia with levamisole

“…Agranulocytosis has been better studied and in most cases appears to be due to complement-dependent IgM-mediated peripheral destruction of granulocytes [ 161. Other mechanisms which have been proposed to play a role in levamisole-induced leukopenia include drug-hapten interaction, circulating immune complexes, and putative serum factors causing suppression of bone marrow granulocyte progenitor cells [7,16]. Since levamisole-associated leukopenia may be accompanied by a mild anemia or thrombocytopenia, it is likely that cytopenias arising in these three cell lineages result from a common etiology [61.…”