Evaluation of levamisole as an adjuvant to chemotherapy for treatment of ANLL

Sloten, K. Van; Wiernik, Peter H.; Schiffer, Charles A.; Schimpff, Stephen C.

doi:10.1002/1097-0142(19830501)51:9<1576::aid-cncr2820510904>3.0.co;2-a

Cited by 18 publications

(5 citation statements)

References 9 publications

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“…Patients with AML received an anthracycline and cytosine arabinoside for remission induction therapy [12]. Patients treated in the late 1970s and 1980s received maintenance or intensive maintenance therapy after achieving remission [ 13,141. Patients with ALL were treated with a regimen including vincristine and corticosteroids with or without other drugs as induction therapy and were treated with multidrug regimens during consolidation and maintenance [ 151.…”

Section: Diagnosis Of Leukemiamentioning

confidence: 99%

Association of thyroid disease with acute leukemia

1992

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The purpose of this paper is to evaluate the possible clinical association of autoimmune thyroid disease and acute leukemia. This study is a retrospective review of all adult patients with acute leukemia treated at our institutions from 1978-1989. Those with both leukemia and thyroid disease were evaluated and are presented. Twenty-seven of eight hundred seventy patients with acute leukemia had evidence of thyroid disease. This is a 3-fold increase in overall incidence. Twenty-one patients had acute myeloid leukemia, five had acute lymphoid leukemia, and one had accelerated chronic myeloid leukemia. Thyroid disease entities included toxic multinodular goiter (four patients), idiopathic hypothyroidism (eight patients), Graves' disease (eight patients), and Hashimoto's thyroiditis (seven patients). Whereas the association may have had a negative effect on elderly patients, those with Graves' disease and Hashimoto's disease appeared to have an improved outcome of the leukemia. There is an increased association of autoimmune thyroid disease and acute leukemia. Since thyroid hormones are important regulators of hematopoiesis and utilize receptors similar to those of differentiating factors such as retinoids, the association may be important for further study of mechanisms of growth regulations in leukemia.

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Section: Diagnosis Of Leukemiamentioning

confidence: 99%

Association of thyroid disease with acute leukemia

1992

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“…Previous clinical studies with levamisole in AML focused primarily on its use as post-remission therapy, and limited data exist on its use in patients with active leukemia. In a study reported by Van Sloten et al, 16 post-remission therapy with levamisole at a dose of 90 mg/m 2 daily failed to improve disease-free survival in patients with AML compared to observation, suggesting minimal, if any, antileukemic activity. A synergistic effect of the combination of HCG and levamisole, however, cannot be ruled out as an explanation for the observed effects in patients and in patient-derived leukemic cells sampled during therapy.…”

Section: Discussionmentioning

confidence: 93%

In vitro effects and clinical evaluation of a human chorionic gonadotrophin preparation in acute leukemia

et al. 1998

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Commercial human chorionic gonadotrophin (HCG) preparations decrease the tumorigenicity of human tumors in immunodeficient mice and induce apoptotic cell death in animal tumor models. Preliminary studies in humans have demonstrated tumor regression in patients with Kaposi's sarcoma given intralesional injections of HCG. To further evaluate HCG's antitumor activity we conducted in vitro and clinical evaluations of HCG in acute myeloid leukemia (AML). In HL-60 leukemic cell lines, a 20-40% inhibition of cell density was demonstrated by trypan blue exclusion method at low concentrations of an HCG preparation (2 ؋ 10 −3 -2 ؋ 10 −2 ). Similar concentrations also resulted in a reduction in the proportion of cells in G 2 M phase of the cell cycle, as well as enhanced differentiation compared to control cells. Fifteen patients with advanced AML with marrow blast counts Ͼ30%, and five with marrow blast counts 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/ l and percent blasts in the marrow ranging from 16 to 81% were observed to have no progressive increase in either marrow or peripheral blast counts for 70-121 days. One patient with a pretreatment blast count of 10% in the marrow, no circulating blasts and minor cytopenias had a decrease in marrow blasts to less than 5% which has persisted at 550 days. No significant improvement from baseline levels of neutrophils, hemoglobin or platelets were observed in any of the patients treated. Increases in apoptotic cell death were observed in over 50% of patients' cells with some demonstrating peak levels similar to experiences in patients treated with DNA-damaging chemotherapy. A decreased expression of bcl-2 was seen in the majority of patients ranging from 6 to 62%. These new observations suggest that HCG preparations may inhibit leukemic cell growth through enhancement of cell death mechanisms and could be used in judicious combinations with other approaches. The results confirm the pro-apoptotic 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 important in its development as a clinically useful agent.

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“…In clinical leukemia chemotherapy, especially for acute myeloid leukemia, the combination of anthracycline and Ara-C exhibits synergistic antitumor activity. [15][16][17][18] So, there is a discrepancy between the clinical efficacy and our basic results. However, we only examined the uptake of DOX, i.e., we did not assess the uptake of Ara-C or their pharmacological interaction.…”

Section: Discussionmentioning

confidence: 95%

Contribution of the Nucleoside Transport System to Doxorubicin Transport in HL60 Cells but Not in Mononuclear Cells

Nagasawa

Fumihara

Ohnishi

et al. 1999

Japanese Journal of Cancer Research

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Previously, we reported that pirarubicin (THP), an anthracycline, was transported, at least in part, via a nucleoside transport system in human leukemic HL60 cells, but not in mononuclear cells (MNCs). In this study, the contribution of the nucleoside transport system to the transport of other anthracyclines, doxorubicin (DOX), daunorubicin (DNR) and idarubicin (IDA), in HL60 cells and MNCs was investigated. The experiments were performed after both types of cells had been pretreated with a metabolic inhibitor, 2,4-dinitrophenol, to deplete cellular ATP. The DOX uptake by HL60 cells was partially inhibited by inhibitors of equilibrative nucleoside transporters. In HL60 cells, moreover, the uptake of DOX depended on an inwardly directed Na + -gradient, and was inhibited by concentrative nucleoside transporters, but there was no change in the DNR or IDA uptake under any of these conditions. On the other hand, the uptake of the three drugs by MNCs was not affected by any inhibitors of the nucleoside transporters, and there was no dependence of the uptake on an Na + -gradient. These results suggested that DOX, but not DNR or IDA, was partially transported in HL60 cells via the nucleoside transport system, whereas in MNCs the system did not contribute to the uptake of any of these three drugs. Thus, nucleoside transport systems contributing to the transport of anthracyclines may be different among different derivatives and cell types.

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Evaluation of levamisole as an adjuvant to chemotherapy for treatment of ANLL

Cited by 18 publications

References 9 publications

Association of thyroid disease with acute leukemia

Association of thyroid disease with acute leukemia

In vitro effects and clinical evaluation of a human chorionic gonadotrophin preparation in acute leukemia

Contribution of the Nucleoside Transport System to Doxorubicin Transport in HL60 Cells but Not in Mononuclear Cells

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