The combination of intermediate doses of thalidomide and dexamethasone reduces bone marrow micro-vessel density but not serum levels of angiogenic cytokines in patients with refractory/relapsed multiple myeloma

Hematological Oncology

Volumn 22, Issue 4, 2004, Pages 159-168

  Hatjiharissi, E ^a   Terpos, Evangelos ^b,d   Papaioannou, M ^a   Hatjileontis, C ^c   Kaloutsi, V ^c   Galaktidou, G ^a   Gerotziafas, G ^a   Christakis, J ^a   Zervas, K ^a  

^a Department of Oral and Maxillofacial Surgery   (Greece)

^b 251 GENERAL AIR FORCE HOSPITAL   (Greece)

^c ARISTOTLE UNIVERSITY OF THESSALONIKI   (Greece)

^d NONE   (Greece)

Author keywords

Angiogenesis; Dexamethasone; Microvessel density; Multiple myeloma; Thalidomide

Indexed keywords

BASIC FIBROBLAST GROWTH FACTOR; CYTOKINE; DEXAMETHASONE; INTERLEUKIN 1BETA; INTERLEUKIN 6; INTERLEUKIN 6 RECEPTOR; THALIDOMIDE; TRANSFORMING GROWTH FACTOR ALPHA; TUMOR NECROSIS FACTOR ALPHA; VASCULOTROPIN;

ADULT; AGED; ANTIANGIOGENIC ACTIVITY; ARTICLE; BONE MARROW BIOPSY; CANCER RELAPSE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE RESPONSE; DRUG EFFICACY; DRUG RESPONSE; FEMALE; HUMAN; HUMAN TISSUE; MALE; MULTIPLE MYELOMA; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; REFRACTORY PERIOD;

AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BONE MARROW; CYTOKINES; DEXAMETHASONE; FEMALE; FIBROBLAST GROWTH FACTOR 2; HUMANS; INTERLEUKIN-1; INTERLEUKIN-6; MALE; MIDDLE AGED; MULTIPLE MYELOMA; NEOPLASM PROTEINS; NEOVASCULARIZATION, PATHOLOGIC; RECEPTORS, INTERLEUKIN-6; SALVAGE THERAPY; SOLUBILITY; THALIDOMIDE; TREATMENT OUTCOME; TUMOR NECROSIS FACTOR-ALPHA; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 25144517719     PISSN: 02780232     EISSN: None     Source Type: Journal    
DOI: 10.1002/hon.738     Document Type: Article

References (46)

1. Blade J, San Miguel JF, Fontanillas M, et al. Increased conventional chemotherapy does not improve survival in multiple myeloma: long-term results of two trials including 914 patients. Hematol J 2001; 2: 272-278.
2. Child JA, Morgan GJ, Davies FE, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003; 348: 1875-1883.
3. Terpos E, Apperley JF, Samson D, et al. Autologous stem cell transplantation in multiple myeloma: improved survival in nonsecretory multiple myeloma but lack of influence of age, status at transplant, previous treatment and conditioning regimen. A single-centre experience in 127 patients. Bone Marrow Transplant 2003; 31: 163-170.
4. Singhal S, Mehta J, Desikan R, et al. Anti tumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999; 341: 1566-1571.
5. Rajkumar SV, Leonard JP, Pekle K, Lyons L, Michaeli J. Thalidomide for previously untreated indolent or smoldering multiple myeloma. Leukemia 2001; 15: 1274-1276.
6. Parman T, Wiley MJ, Wells PG. Free radical-mediated oxidative DNA damage in the mechanism of thalidomide teratogenicity. Nat Med 1999; 5: 582-585.
7. Hideshima T, Chauhan D, Shima Y, et al. Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood 2000; 96: 2943-2950.
8. Geitz H, Handt S, Zwingenberger K. Thalidomide selectively modulates the density of cell surface molecules involved in the adhesion cascade. Immunopharmacology 1996; 31: 213-221.
9. Mitsiades N, Mitsiades CS, Poulaki V, et al. Biologic sequelae of nuclear factor-kappaB blockade in multiple myeloma: therapeutic application. Blood 2002; 99: 4079-4086.
10. Davies FE, Raje N, Hideshima T, et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 2001; 98: 210-216.
11. D'Amato RJ, Loughnan MS, Flynn E, Folkman J. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 1994; 91: 4082-4085.
12. Pruneri G, Ponzoni M, Ferreri AJ, et al. Microvessel density, a surrogate marker of angiogenesis, is significantly related to survival in multiple myeloma patients. Br J Haematol 2002; 118: 817-820.
13. Rajkumar SV, Leong T, Roche PC, et al. Prognostic value of bone marrow angiogenesis in multiple myeloma. Clin Cancer Res 2000; 6: 3111-3116.
14. Kumar S, Fonseca R, Dispenzieri A, et al. Bone marrow angiogenesis in MM: effect of therapy. Br J Haematol 2002; 119: 665-671.
15. Kumar S, Gertz MA, Dispenzieri A, et al. Prognostic value of bone marrow angiogenesis in patients with multiple myeloma undergoing high-dose therapy. Bone Marrow Transplant 2004; 34: 235-239.
16. Podar K, Anderson KC. The pathophysiological role of VEGF in hematological malignancies: therapeutic implications. Blood 2005; 105: 1383-1395.
17. 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 multiple myeloma. Eur J Haematol 2001; 66: 83-88.
18. Iwasaki T, Hamano T, Ogata A, Hashimoto N, Kitano M, Kakishita E. Clinical significance of vascular endothelial growth factor and hepatocyte growth factor in multiple myeloma. Br J Haematol 2002; 116: 796-802.
19. 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.
20. Rajkumar SV, Fonseca R, Witzig TE, Gertz MA, Greipp PR. Bone marrow angiogenesis in patients achieving complete response after stem cell transplantation for multiple myeloma. Leukemia 1999; 13: 469-472.
21. Kumar S, Witzig TE, Dispenzieri A, et al. Effect of thalidomide therapy on bone marrow angiogenesis in multiple myeloma. Leukemia 2004; 18: 624-627.
22. Du W, Hattori Y, Hashiguchi A, et al. Tumor angiogenesis in the bone marrow of multiple myeloma patients and its alteration by thalidomide treatment. Pathol Int 2004; 54: 285-294.
23. Dimopoulos MA, Zervas K, Kouvatseas G, et al. Thalidomide and dexamethasone combination for refractory multiple myeloma. Ann Oncol 2001; 12: 991-995.
24. Blade J, Samson D, Reece D, et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. Br J Haematol 1998; 102: 1115-1123.
25. Munshi NC, Wilson C. Increased bone marrow microvessel density in newly diagnosed multiple myeloma carries a poor prognosis. Semin Oncol 2001; 28: 565-569.
26. Rajkumar SV, Mesa RA, Fonseca R, et al. Bone marrow angiogenesis in 400 patients with monoclonal gammopathy of undetermined significance, multiple myeloma, and primary amyloidosis. Clin Cancer Res 2002; 8: 2210-2216.
27. Kumar S, Witzig TE, Greipp PR, Rajkumar SV. Bone marrow angiogenesis and circulating plasma cells in multiple myeloma. Br J Haematol 2003; 122: 272-274.
28. Kumar S, Witzig TE, Timm M, et al. Bone marrow angiogenic ability and expression of angiogenic cytokines in myeloma: evidence favoring loss of marrow angiogenesis inhibitory activity with disease progression. Blood 2004; 104: 1159-1165.
29. Brunner G, Nguyen H, Gabrilove J, Rifkin DB, Wilson EL. Basic fibroblast growth factor expression in human bone marrow and peripheral blood cells. Blood 1993; 81: 631-638.
30. Gupta D, Treon SP, Shima Y, et al. Adherence of myeloma cells to bone marrow stromal cells upregulates VEGF secretion. Therapeutic applications. Leukemia 2001; 15: 1950-1961.
31. Kumar S, Witzig TE, Timm M, et al. Expression of VEGF and its receptors by myeloma cells. Leukemia 2003; 17: 2025-2031.
32. Politou M, Terpos E, Crawley D, et al. Pre-transplant VEGF levels in multiple myeloma are predictive for progression free survival. Hematol J 2004; 5(Suppl. 2): S13(abstract).
33. Ribas C, Colleoni GW, Silva MR, Carregoza MJ, Bordin JO. Prognostic significance of vascular endothelial growth factor immunoexpression in the context of adverse standard prognostic factors in multiple myeloma. Eur J Haematol 2004; 73: 311-317.
34. Tosi P, Zamagni E, Cellini C, et al. Thalidomide alone or in combination with dexamethasone in patients with advanced, relapsed or refractory multiple myeloma and renal failure. Eur J Haematol 2004; 73: 98-103.
35. Rajkumar SV, Hayman S, Gertz MA, et al. Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. J Clin Oncol 2002; 20: 4319-4323.
36. Sezer O, Niemoller K, Kaufmann O, et al. Decrease of bone marrow angiogenesis in myeloma patients achieving a remission after chemotherapy. Eur J Haematol 2001; 66: 238-244.
37. Folkman J. Angiogenesis-dependent diseases. Semin Oncol 2001; 28: 536-542.
38. Browder T, Butterfield CE, Kraling BM, et al. Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res 2000; 60: 1878-1886.
39. Weber DM, Rankin K, Gavino M, et al. Angiogenesis factors and sensitivity to thalidomide in previously untreated multiple myeloma. Blood 2000; 96(Suppl. 1): 168a(abstract).
40. Neben K, Moehler T, Egerer G, et al. High plasma basic fibroblast growth factor concentration is associated with response to thalidomide in progressive multiple myeloma. Clin Cancer Res 2001; 7: 2675-2681.
41. Bertolini F, Mingrone W, Alietti A, et al. Thalidomide in multiple myeloma, myelodysplastic syndromes and histiocytosis. An analysis of clinical results and of surrogate angiogenesis markers. Ann Oncol 2001; 12: 987-990.
42. Banks RE, Forbes MA, Kinsey SE, et al. Release of angiogenic cytokine vascular endothelial growth factor VEGF from platelets: significance for VEGF measurements and cancer biology. Br J Cancer 1998; 77: 956-964.
43. Poon RT, Lau CP, Cheung ST, Yu WC, Fan ST. Quantitative correlation of serum levels and tumour expression of vascular endothelial growth factor in patients with hepatocellular carcinoma. Cancer Res 2003; 63: 3121-3126.
44. Dankbar B, Padro T, Leo R, et al. Vascular endothelial growth factor and interleukin-6 in paracrine tumour stromal interactions in multiple myeloma. Blood 2000; 95: 2630-2636.
45. Anderson KC, Lust JA. Role of cytokines in multiple myeloma. Sem Hematol 1999; 36(Suppl. 3): 14-20.
46. Kyrtsonis MC, Dedousis G, Zervas C, et al. Soluble Interleukin-6 Receptor (sIL-6R): a new prognostic factor in multiple myeloma. Br J Haematol 1996; 93: 398-400.