A broad range of biologic and clinical studies of multiple myeloma will be conducted to define the mechanisms of drug resistance. Laboratory research will be integrated with a clinical program using high dose melphalan and total body irradiation (supported by bone marrow transplantation) as a consolidation therapy after VAD-induced remission or as a salvage program for VAD failure. The main clinical goal is to maximize tumor cytoreduction using 2 highly effective and non-cross resistant regimens, so that long term disease control and perhaps cure of this B cell neoplasm can be accomplished. Laboratory studies will define the myeloma tumor genotype and phenotypic features associated with drug resistance and examine relapse in the context of clonal evaluation. In this endeavor, cytometric, cytogenetic and molecular genetic studies will be employed to provide a comprehensive evaluation of myeloma plasma cells during defined stages of the clinical program at diagnosis, in remission and at relapse. The unique therapeutic approach will provide the great opportunity to study fundamentally important areas of myeloma and cancer biology in general, i.e. clonal evaluation, drug resistance and potential obstacles to cure despite supralethal cytotoxic therapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
3R01CA037161-06S1
Application #
3174921
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Project Start
1984-09-01
Project End
1992-09-29
Budget Start
1989-09-30
Budget End
1992-09-29
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Arkansas for Medical Sciences
Department
Type
Schools of Medicine
DUNS #
City
Little Rock
State
AR
Country
United States
Zip Code
72205
Ridley, R C; Xiao, H; Hata, H et al. (1993) Expression of syndecan regulates human myeloma plasma cell adhesion to type I collagen. Blood 81:767-74
Hata, H; Xiao, H; Petrucci, M T et al. (1993) Interleukin-6 gene expression in multiple myeloma: a characteristic of immature tumor cells. Blood 81:3357-64
Kreitman, R J; Siegall, C B; FitzGerald, D J et al. (1992) Interleukin-6 fused to a mutant form of Pseudomonas exotoxin kills malignant cells from patients with multiple myeloma. Blood 79:1775-80
Thomas, X; Xiao, H Q; Chang, R et al. (1992) Circulating B lymphocytes in multiple myeloma patients contain an autocrine IL-6 driven pre-myeloma cell population. Curr Top Microbiol Immunol 182:201-7
Barlogie, B; Gale, R P (1992) Multiple myeloma and chronic lymphocytic leukemia: parallels and contrasts. Am J Med 93:443-50
Jagannath, S; Vesole, D H; Glenn, L et al. (1992) Low-risk intensive therapy for multiple myeloma with combined autologous bone marrow and blood stem cell support. Blood 80:1666-72
Alexanian, R; Barlogie, B; Gutterman, J (1991) Alpha-interferon combination therapy of resistant myeloma. Am J Clin Oncol 14:188-92
Barlogie, B; Gahrton, G (1991) Bone marrow transplantation in multiple myeloma. Bone Marrow Transplant 7:71-9
Dimopoulos, M A; Barlogie, B; Smith, T L et al. (1991) High serum lactate dehydrogenase level as a marker for drug resistance and short survival in multiple myeloma. Ann Intern Med 115:931-5
Barlogie, B (1990) Management of multiple myeloma. Blut 60:1-7

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