Ej. Feldman et al., IN-VITRO EFFECTS AND CLINICAL-EVALUATION OF A HUMAN CHORIONIC-GONADOTROPIN PREPARATION IN ACUTE-LEUKEMIA, Leukemia, 12(11), 1998, pp. 1749-1755
Commercial human chorionic gonadotrophin (HCG) preparations decrease t
he tumorigenicity of human tumors in immunodeficient mice and induce a
poptotic cell death in animal tumor models. Preliminary studies in hum
ans have demonstrated tumor regression in patients with Kaposi's sarco
ma given intralesional injections of HCG. To further evaluate HCG's an
titumor activity we conducted in vitro and clinical evaluations of HCG
in acute myeloid leukemia (AML). In HL-60 leukemic cell lines, a 20-4
0% inhibition of cell density was demonstrated by trypan blue exclusio
n method at low concentrations of an HCG preparation (2 x 10(-3)-2 x 1
0(-2)). Similar concentrations also resulted in a reduction in the pro
portion of cells in G(2)M phase of the cell cycle, as well as enhanced
differentiation compared to control cells. Fifteen patients with adva
nced AML with marrow blast counts >30%, and five with marrow blast cou
nts between 10 and 26% were given daily subcutaneous injections of HCG
2-4 IU and oral levamisole 50 mg weekly. Five patients with absolute
blast counts in the blood ranging from 0 to 3500/mu l and percent blas
ts in the marrow ranging from 16 to 81% were observed to have no progr
essive increase in either marrow or peripheral blast counts for 70-121
days. One patient with a pretreatment blast count of 10% in the marro
w, no circulating blasts and minor cytopenias had a decrease in marrow
blasts to less than 5% which has persisted at 550 days. No significan
t improvement from baseline levels of neutrophils, hemoglobin or plate
lets were observed in any of the patients treated. Increases in apopto
tic cell death were observed in over 50% of patients' cells with some
demonstrating peak levels similar to experiences in patients treated w
ith DNA-damaging chemotherapy. A decreased expression of bcl-2 was see
n in the majority of patients ranging from 6 to 62%. These new observa
tions suggest that HCG preparations may inhibit leukemic cell growth t
hrough enhancement of cell death mechanisms and could be used in judic
ious combinations with other approaches. The results confirm the pro-a
poptotic effects of HCG preparations reported in patients with Kaposi'
s sarcoma. Identification of the active component of HCG preparations
and further understanding of its growth modulatory action will be impo
rtant in its development as a clinically useful agent.