Patients with multiple myeloma treated with thalidomide: evaluation of clinical parameters, cytokines, angiogenic markers, mast cells and marrow CD57+ cytotoxic T cells as predictors of outcome

Mileshkin, Linda; Hönemann, Dirk; Gambell, Peter; Trivett, Melanie; Hayakawa, Yoshihiro; Smyth, Mark J.; Beshay, Victoria; Ritchie, David; Simmons, Paul J.; Milner, Alvin; Zeldis, Jerome B.; Prince, H. Miles

doi:10.3324/haematol.11208

Cited by 37 publications

(26 citation statements)

References 39 publications

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“…In multiple myeloma, vascular endothelial growth factor was produced by malignant plasma cells and stimulates the proliferation of endothelial cells, also at the same time, vascular endothelial growth factor had secreted by endothelial cells in the tumor microenvironment it acted in an autocrine and paracrine way on both endothelial and myeloma cells, so there was a reciprocal stimulation between endothelial cells and myeloma cells to produce it [12] . A significant increment in plasma level of vascular endothelial growth factor and its soluble receptor -2 in myeloma patients at diagnosis before starting chemotherapy protocol with significant decrement in there plasma levels after four courses of VAD protocol of therapy in responded patients and this was consistent with same data observed by Mileskhin et al who reported that high levels of vascular endothelial growth factor were associated with response rate in patients treated chemotherapy [13,16] . Anther contradictory results were detected by Cibeira and collaborators who noticed that there was not a significant correlation between response rate and vascular endothelial growth factor level or its receptor-2 [14,15] and this might attributed to different in selection criteria of patients or method of assessment as the concentrations of angiogenesis factors in the plasma rather than in the serum because platelets contain significant concentrations of these cytokines, released during during preparation of serum [6,17] .…”

Section: Discussionsupporting

confidence: 88%

Predictive and Prognostic Significance of Vascular Endothelial Growth Factor (VEGF) and Response to VAD Protocol of Chemotherapy In Multiple Myeloma Patients

Hefni

Ebian²

2015

International Journal of Hematology Research

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other bad prognostic factors such as stage, high B2 macroglobulin level in multiple myeloma patients ,and when multi analysis was applied a high significant association were observed reflecting an independent risk of vascular endothelial growth factor, or its soluble receptor-2, ten myeloma patients (17.8%) showed complete response, while twenty seven (48.2%) patients showed either very good or partial response and rest patient showed no response with tolerated toxicity according to WHO criteria of toxicity and the median time to progression for responders was 22.5 months while 95% confidence interval (CI) was 1.71-3.09. CONCLUSION: Vascular endothelial growth factor and its soluble receptor -2 had a prognostic and predictive utility in responded multiple myeloma patient indicating that the rate of angiogenesis was decreased after successful treatment and might open a future direction for target therapy

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Section: Discussionsupporting

confidence: 88%

Predictive and Prognostic Significance of Vascular Endothelial Growth Factor (VEGF) and Response to VAD Protocol of Chemotherapy In Multiple Myeloma Patients

Hefni

Ebian²

2015

International Journal of Hematology Research

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“…There are contradictory reports VGPR very good partial response, PR partial response, IR insufficient response, VEGF vascular endothelium growth factor, HGF hepatocyte growth factor, TSP-1 thrombospondin-1 on the correlation between VEGF level and prognosis. Mileskhin et al reported that high levels of VEGF were associated with response rate in patients treated with thalidomide [21]. On the other hand, Cibeira and collaborators have not confirmed any correlation between response rate and VEGF level [22].…”

Section: Discussionmentioning

confidence: 90%

Levels of angiogenic factors in patients with multiple myeloma correlate with treatment response

Pour¹,

Šváchová²,

Adam³

et al. 2009

Ann Hematol

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Angiogenesis plays a significant role in the pathogenesis of multiple myeloma (MM). We have measured concentrations of angiogenesis activators, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor, and hepatocyte growth factor (HGF), and inhibitors, including endostatin, thrombospondin-1 (TSP-1), and angiostatin in the peripheral and bone marrow blood of MM patients at diagnosis and after high-dose chemotherapy. We have analyzed 96 patients with secretory MM. Serial measurements of angiogenesis factors/inhibitors were analyzed in the plasma by subgroups based on the best treatment response. Concentrations of angiogenic factors were determined in the peripheral blood and bone marrow plasma. There were significant decreases of VEGF and HGF levels and a significant increase in TSP-1 concentrations in the bone marrow plasma of patients who achieved complete or very good partial response in contrast to those who had partial or no response. VEGF and HGF levels decrease but those of TSP-1 increase after successful treatment for MM, indicating a reduction in the rate of angiogenesis.

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“…Finally, Mileshkin et al showed in 75 patients with relapsed/refractory MM who received thalidomide that responders had a reduction of BM-MVD and both plasma and BM-plasma levels of VEGF. In the same study, baseline elevated VEGF levels Novel anti-myeloma agents and angiogenesis 681 predicted for a better response rate and superior progression-free survival [72]. Lenalidomide (Revlimid 1 ) is a potent thalidomide analogue with also documented efficacy in MM patients [73,74].…”

Section: Immunomodulatory Drugs (Imids)mentioning

confidence: 98%

Novel anti-myeloma agents and angiogenesis

Anargyrou

Dimopoulos

Sezer

et al. 2008

Leukemia & Lymphoma

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During the last decade several novel agents have been used in the management of patients with multiple myeloma. Immunomodulatory drugs and proteasome inhibitors exert their efficacy both directly by inducing apoptosis of myeloma cells and indirectly through the interruption of the interactions between myeloma and stromal cells in the bone marrow (BM) microenvironment. These interactions are crucial for myeloma cell growth and survival. The adherence of myeloma cells to BM stromal cells leads to the overproduction of several cytokines with angiogenic properties that enhance the survival and growth of myeloma cells through paracrine and autocrine loops. The correlation of these molecules with clinical features and survival of myeloma patients supports the importance of angiogenesis in the pathogenesis of the disease and reveals these cytokines as suitable targets for the development of novel anti-myeloma therapies. This review summarises all available preclinical and clinical data for the effect of novel agents that are used in myeloma therapy, such as thalidomide, lenalidomide, bortezomib and VEGF inhibitors, on angiogenesis, which is at least partially responsible for their remarkable anti-myeloma efficacy.

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Patients with multiple myeloma treated with thalidomide: evaluation of clinical parameters, cytokines, angiogenic markers, mast cells and marrow CD57+ cytotoxic T cells as predictors of outcome

Cited by 37 publications

References 39 publications

Predictive and Prognostic Significance of Vascular Endothelial Growth Factor (VEGF) and Response to VAD Protocol of Chemotherapy In Multiple Myeloma Patients

Predictive and Prognostic Significance of Vascular Endothelial Growth Factor (VEGF) and Response to VAD Protocol of Chemotherapy In Multiple Myeloma Patients

Levels of angiogenic factors in patients with multiple myeloma correlate with treatment response

Novel anti-myeloma agents and angiogenesis

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