Levamisole: evidence for activity on human haemopoietic progenitor cells

Senn, J. S.; Lai, Chen-Yi; Price, Gerald B.

doi:10.1038/bjc.1980.5

Cited by 11 publications

(3 citation statements)

References 14 publications

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“…Evidence is available that LMS may favor marrow restoration after chemotherapy [10]. Also, enhanced granulopoietic colony formation was observed when LMS was cocultured with human bone marrow stem cells in leukocyte-conditioned medium through promoting the release of colony-stimulating activity [11]. Previously, we reported the short-term effectiveness of CSA&LMS regimen in a small group of patients with refractory or relapsed SAA [12].…”

Section: Introductionmentioning

confidence: 99%

Outcome of a novel immunosuppressive strategy of cyclosporine, levamisole and danazol for severe aplastic anemia

Wang

Shi

et al. 2015

Int J Hematol

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Treatment options for patients with severe aplastic anemia (SAA) in developing countries are limited. A cohort of 261 patients with SAA received a novel immunosuppressive strategy of cyclosporine alternately combined with levamisole plus danazol (CSA&LMS-based regimen), which included 70 VSAA and 191 moderate SAA [initial absolute neutrophil count (ANC) >200/μL] cases. The CSA&LMS-based regimen was administrated orally with an initial dose of CSA 3 mg/kg in adults and 5 mg/kg in children every other day, LMS 150 mg in adults and 2.5 mg/kg in children every other day, and danazol (5.0-10.0) mg/kg daily, continued for 12 more months, followed by slow tapering. The 6-month response rates were 24.3 and 52.9 % for VSAA and moderate SAA (P < 0.001), respectively. Univariate and multivariate analyses demonstrated that younger age, higher pretreatment absolute reticulocyte count and ANC were favorable factors for achieving response at 6 months. The estimated 5-year overall survival rates were 33.8 % (95 % CI 20.6-47 %) and 80.5 % (95 % CI 69.7-91.3 %) for VSAA and moderate SAA, respectively (P < 0.001). To date, nine patients relapsed, and six patients evolved to clonal disorders. Thus, CSA&LMS-based regimen may represent a promising immunosuppressive strategy for moderate SAA.

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Section: Introductionmentioning

confidence: 99%

Outcome of a novel immunosuppressive strategy of cyclosporine, levamisole and danazol for severe aplastic anemia

Wang

Shi

et al. 2015

Int J Hematol

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“…Early evidence showed that LMS favored marrow restoration [17] and enhanced the numbers of granulocyte colony units [18]. More importantly, up to 91.5% of moderate AA responded to a novel immunosuppressive strategy of CsA alternately combined with LMS (CsA + LMS regimen) in our pilot study [19].…”

Section: Introductionmentioning

confidence: 82%

Cyclosporine Combined with Levamisole for Lower-Risk Myelodysplastic Syndromes

Li¹,

Shi²,

Wang³

et al. 2015

Acta Haematol

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Clinical and experimental evidence suggests an immune-mediated pathophysiology in subjects with lower-risk myelodysplastic syndromes (MDS) in whom immunosuppressive therapy may be effective. The novel immunosuppressive strategy of cyclosporine A (CsA) alternately combined with levamisole (LMS; CsA + LMS regimen) can dramatically improve the response rate and survival in aplastic anemia from those of our previous study. Herein, we retrospectively analyzed the data of 89 lower-risk MDS patients who received the CsA + LMS regimen. A total of 63 patients (70.8%) achieved either complete remission or hematological improvement at 4 months. Overall, 51, 41 and 19 patients had erythroid, platelet and neutrophil responses, respectively. Following the CsA + LMS regimen, 6 patients progressed to more advanced MDS at a median interval of 5 months (range, 3-42 months). The estimated 24-month progression-free survival was 82.2% (95% CI, 72.84-91.56) for all patients. Within the median follow-up of 18.5 months (range, 7.0-61.0), 6 patients died. In conclusion, the CsA + LMS regimen alleviated cytopenias and improved survival and freedom from evolution, suggesting that it could be reserved as an alternative choice for lower-risk MDS.

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“…Levamisole (LMS), originally designed for anthelminthic applications, has subsequently been reported to have a wide range of immunomodulatory effects and is widely used in the adjuvant therapy of autoimmune diseases and malignant tumors ( 14 , 15 ). Previous studies revealed that LMS promoted recovery of BM in patients who received chemotherapy by restoring the Th1/Th2 cell ratio to normal ( 16 ) and increasing the formation of granulocyte colony units ( 17 ). Efficacy of LMS treatment remains dose-dependent; which a low dose of LMS can induce dendritic cell maturation and stimulate T-cell activation but a high dose exerts inhibitory effects ( 18 , 19 ).…”

Section: Introductionmentioning

confidence: 99%

Levamisole Suppresses CD4+ T-Cell Proliferation and Antigen-Presenting Cell Activation in Aplastic Anemia by Regulating the JAK/STAT and TLR Signaling Pathways

et al. 2022

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Aplastic anemia (AA) is a life-threatening disease primarily caused by a metabolic disorder and an altered immune response in the bone marrow (BM) microenvironment, where cytotoxic immune cells attack resident cells and lead to hematopoietic failure. We previously reported an efficient strategy by applying cyclosporin (CSA) combined with levamisole (CSA+LMS-based regimen) in the treatment of AA, but the immunoregulatory mechanism of LMS was still unclear. Here, the therapeutic effects of LMS were examined in vivo using the BM failure murine model. Meanwhile, the proportion and related function of T cells were measured by flow cytometry in vivo and in vitro. The involved signaling pathways were screened by RNA-seq and virtual binding analysis, which were further verified by interference experiments using the specific antagonists on the targeting cells by RT-PCR in vitro. In this study, the CSA+LMS-based regimen showed a superior immune-suppressive response and higher recession rate than standard CSA therapy in the clinical retrospective study. LMS improved pancytopenia and extended the survival in an immune-mediated BM failure murine model by suppressing effector T cells and promoting regulatory T-cell expansion, which were also confirmed by in vitro experiments. By screening of binding targets, we found that JAK1/2 and TLR7 showed the highest docking score as LMS targeting molecules. In terms of the underlying molecular mechanisms, LMS could inhibit JAK/STAT and TLR7 signaling activity and downstream involved molecules. In summary, LMS treatment could inhibit T-cell activation and downregulate related molecules by the JAK/STAT and TLR signaling pathways, supporting the valuable clinical utility of LMS in the treatment of AA.

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Levamisole: evidence for activity on human haemopoietic progenitor cells

Cited by 11 publications

References 14 publications

Outcome of a novel immunosuppressive strategy of cyclosporine, levamisole and danazol for severe aplastic anemia

Outcome of a novel immunosuppressive strategy of cyclosporine, levamisole and danazol for severe aplastic anemia

Cyclosporine Combined with Levamisole for Lower-Risk Myelodysplastic Syndromes

Levamisole Suppresses CD4+ T-Cell Proliferation and Antigen-Presenting Cell Activation in Aplastic Anemia by Regulating the JAK/STAT and TLR Signaling Pathways

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