Concentration of hepatocyte growth factor and thrombospondin predict treatment response in patients with multiple myeloma
Authors:
H. Šváchová 1; L. Pour 2; M. Almaši 1; P. Němec 3; D. Králová 1; L. Kovářová 4; M. Penka 5; J. Vorlíček 2; R. Hájek 1,2,4
Authors‘ workplace:
Univerzitní výzkumné centrum – Česká myelomová skupina, Lékařská fakulta MU Brno, 2Interní hematoonkologická klinika, FN a LF MU Brno, 3Oddělení genetiky a molekulární biologie, Ústav experimentální biologie, Přírodovědecká fakulta MU Brno, 4Laboratoř exp
1
Published in:
Transfuze Hematol. dnes,16, 2010, No. 1, p. 30-34.
Category:
Comprehensive Reports, Original Papers, Case Reports
Overview
Introduction:
Multiple myeloma (MM) is hematological malignancy in which has been demonstrated increased level of angiogenesis. High levels of hepatocyte growth factor (HGF) in myeloma patients undergoing conventional and thalidomide therapy are connected with worse prognosis. Our previous results confirmed that low levels of angiogenesis inhibitor thrombospondin correlated with a poor prognosis after autologous transplantation. We hypothesised that high levels of thrombospondin and low levels of HGF correlate with a good response after bortezomib treatment. Methods and patients: Levels of HGF were measured in peripheral blood and thrombospondin in bone marrow in total of 58 patients at the diagnosis. Patients were divided according to treatment response into the groups: complete remission (CR), very good partial remission (VGPR) and partial remission (PR). Patients with a stable (SD) or progressive disease (PG) were linked together into one group without response (NoR). Results: Patients who achieved CR had significantly lower levels of HGF at the diagnosis than others (p = 0,014), similarly for cut-off level of VGPR (p = 0,012). Patients who achieved CR had significantly higher levels of thrombospondin at the start of therapy (p = 0,002), similarly for cut-off level of VGPR (p = 0,014). Neither concentration of thrombospondin in bone marrow nor HGF in peripheral blood differentiated among groups of patients compared using the Kruskal-Wallis ANOVA test: for thrombospondin (p = 0,063), for HGF (p = 0,077). Conclusion: High level of thrombospondin in patients with a good response to bortezomib treatment is a new, not yet published, prognostic factor. On the basis of lower level of angiogenesis activator HGF in patients with a good response and confirmed significance of achieved treatment response, as a respected prognostic factor, levels of thrombospondin and HGF at start of treatment can become an important predictor of treatment response.
Key words:
multiple myeloma, angiogenesis, HGF, thrombospondin, bortezomib
Sources
1. Vacca A, Ribatti D, Roncali L, et al. Bone marrow angiogenesis and, progression in multiple myeloma. Br J Haematol 1994; 87: 503–508.
2. Rajkumar SV, Leong T, Roche PC, et al. Prognostic value of bone marrow angiogenesis in multiple myeloma. Clin Cancer Res 2000; 6: 3111–3116.
3. Rajkumar SV, Yoon SY, Li CY, et al. Angiogenesis in myeloma: expression, of basic, fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and their receptors by neoplastic plasma cells. Blood 1999; 94: 303b.
4. Neben K, Moehler T, Kraemer A, et al. Response to thalidomide in, progressive multiple, myeloma is not mediated by inhibition of angiogenic, cytokine secretion. Br J Haematol 2001; 115: 605–608.
5. Sezer O, Jakob C, Eucker J, et al. Serum levels of the angiogenic cytokines basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in muliple myeloma. Eur J Haematol 2001; 66: 83–88.
6. Ščudla V, Bačovský J, Papajík T, et al. Comparison of serum levels of, selected biological parameters in monoclonal gammopathy of, undetermined significance and multiple myeloma. Vnitr Lek 2006; 52: 232–240.
7. Alexandrakis MG, Passam FH, Sfiridaki A, et al. Elevated serum concentration of hepatocyte growth factor in patients with multiple myeloma: correlation with markers of disease activity. Am J Hematol 2003; 72: 229–233.
8. Pour L, Svachova H, Adam Z, et al. Pretreatment hepatocyte growth factor .and thrombospondin-1 levels predict response to high-dose chemotherapy for multiple myeloma, Neoplasma, in print.
9. Standal T, Abildgaard N, Fagerli U, et al. HGF inhibits BMP-induced osteoblastogenesis: possible implications for the bone disease of multiple myeloma. Blood 2007; 109: 3024–3030.
10. Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003; 348: 2609–2617.
11. San Miguel JF, Schlag R, Khuageva NK, et al. VISTA Trial Investigators. Bortezomib plus melphalan and prednisone for initial treatment of multiple .myeloma. N Engl J Med 2008; 359: 906–917.
12. Papageorgiou A, Kamat A, Benedict WF, et al. Combination therapy with IFN-alpha plus bortezomib induces apoptosis and inhibits angiogenesis in human bladder cancer cells. Mol Cancer Ther 2006; 5: 3032–3041.
13. Roccaro AM, Hideshima T, Raje N. Bortezomib Mediates Antiangiogenesis in Multiple Myeloma via Direct and Indirect Effects on Endothelial Cells. Cancer Res 2006; 66: 184–191.
14. Terpos E, Kastritis E, Roussou M, et al. The combination of bortezomib, melphalan, dexamethasone and intermittent thalidomide is an effective regimen for relapsed/refractory myeloma and is associated with improvement of abnormal bone metabolism and angiogenesis. Leukemia 2008; 22: 247–256.
15. Politou M, Naresh K, Terpos E, et al. Anti-angiogenic effect of bortezomib in patients with multiple myeloma. Acta Haematol 2005; 114: 170–173.
16. Cibeira MT, Rozman M, Segarra M et al. Bone marrow angiogenesis and angiogenic factors in multiple myeloma treated with novel agents. Cytokine 2008; 41: 244–253.
17. Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia 2009; 23: 3–9.
18. Vacca A, Ribatti D. Bone marrow angiogenesis in multiple myeloma. Leukemia 2006; 20: 193–199.
19. Urbanska-Rys J. High serum level of endostatin in multiple myeloma at diagnosis but not in the plateau phase after treatment. Mediators Inflamm 2003; 12: 229–235.
20. Dmoszynska A, Bojarska-Junak A, Domanski D, et al. Production of proangiogenic cytokines during thalidomide treatment of multiple myeloma. Leuk Lymphoma 2003; 44: 1347–1351.
21. Pour L, Kovarova L, Buchler T, et al. Evaluation of hepatocyte growth factor and endostatin in the bone marrow of patients with multiple myeloma and the effect of peripheral blood admixture. Scripta medica 2009; in print.
22. Barlogie B, Anaissie E, van Rhee F, et al. Incorporating bortezomib into upfront treatment for multiple myeloma: early results of total therapy 3. Br J Haematol 2007; 138: 176–185.
23. Němec P, Grešliková H, Smetana J, et al. The poor prognosis associated with gain/amplification of 1q21 in relapsed multiple myeloma patients may be overcome by Velcade based regimen in contrary of thalidomide based regimen. Haematologica/The Hematology Journal 2008; 93(Suppl 1): 227–228.
24. Sonneveld P, Hajek R, Nagler A, et al. Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapy. DOXIL-MMY-3001 Study Investigators Cancer 2008; 112: 1529–.1537.
25. Barlogie B, Tricot GJ, van Rhee F, et al. Long-term outcome results of the first tandem autotransplant trial for multiple myeloma. Br J Haematol 2006; 135: 158–164.
26. Attal M, Harousseau JL, Facon T, et al. InterGroupe Francophone du Myelome.: Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med, 2003; 349: 2495–2502. Erratum in: N Engl J Med 2004; 350: 2628.
27. Maisnar V, Radocha J, Büchler T, et al. Monotherapy with low-dose thalidomide for relapsed or refractory multiple myeloma: better response rate with earlier treatment. Eur J Haematol 2007; 79: 305–309.
Labels
Haematology Internal medicine Clinical oncologyArticle was published in
Transfusion and Haematology Today
2010 Issue 1
Most read in this issue
- Unsuspected 18F-FDG PET/CT positive findings in the response evaluation or follow-up of non-Hodgkin’s lymphoma patients
- The changes in the nomenclature, classification and diagnostic criteria of myeloproliferative disorders according WHO classification 2008
- News in classification of MDS and evaluation of prognosis by WPSS
- Non-Hodgkinęs lymphomas in childhood in Slovak republic – the incidence and treatment results