pyrophosphate and Multiple-Myeloma

Topics: Adipose Tissue; Autophagy; Bone and Bones; Diphosphates; Humans; Multiple Myeloma; Musculoskeletal Diseases; Osteoarthritis; Osteoporosis, Postmenopausal; Pain

T-cell-mediated immunotherapy is a promising therapeutic option for multiple myeloma (MM). Gamma-delta T cells (gammadelta T cells) recognize phosphoantigens and display strong anti-tumour cytotoxicity. The synthetic agonist Phosphostim (bromohydrin pyrophosphate, BrHPP) has been shown to selectively activate Vgamma9Vdelta2 T cells. This study aimed to evaluate the expansion capacity and anti-myeloma cell cytotoxicity of circulating gammadelta T cells from MM patients at different time points throughout the disease, using Phosphostim and interleukin 2 (IL-2). Circulating gammadelta T cell counts in patients with newly diagnosed MM or in relapse did not differ from those in healthy donors. A 14-d culture of peripheral blood mononuclear cells with Phosphostim and IL-2 triggered a 100-fold expansion of gammadelta T cells in 78% of newly diagnosed patients. Gammadelta T cells harvested at the time of haematopoietic progenitor collection or in relapsing patients expanded less efficiently. Expanded gammadelta T cells killed 13/14 myeloma cell lines as well as primary myeloma cells, but not normal CD34 cells. Their killing efficiency was not affected by 2-d IL-2 starvation. This study demonstrated the ability of Phosphostim and IL-2 to expand gammadelta T cells from MM patients, and the efficient and stable killing of human myeloma cells by gd T cells.

Topics: Adoptive Transfer; Antigens, CD34; CD3 Complex; Cell Line, Tumor; Cell Proliferation; Cytotoxicity, Immunologic; Diphosphates; Female; Humans; Interleukin-2; Lymphocyte Count; Male; Middle Aged; Multiple Myeloma; Receptors, Antigen, T-Cell, gamma-delta; Receptors, CXCR4; T-Lymphocytes

Radiography and scintigraphy were correlated in 70 patients with recently diagnosed, untreated multiple myeloma, including 59 with and 11 without primary lytic bone lesions. A site-by-site comparison showed that scintigraphy was more sensitive than radiography in only 18% of cases, whereas radiography was more sensitive in 38% (p less than 0.001). Patients whose bone scan was as sensitive or more so than the radiograph ("hot" myeloma) had more active disease than those with the "cold" form. Remission was indicated by significant regression or disappearance of scintigraphic abnormalities in 90% of cases. The authors conclude that scintigraphy is not helpful in detecting myelomatous bone lesions, but does have prognostic value for diagnosis and chemotherapy: a positive bone scan indicates initial or residual activity.

Topics: Adult; Aged; Bone and Bones; Bone Neoplasms; Diphosphates; Diphosphonates; Female; Humans; Male; Middle Aged; Multiple Myeloma; Prospective Studies; Radiography; Radionuclide Imaging; Technetium; Technetium Tc 99m Medronate; Technetium Tc 99m Pyrophosphate

Topics: Bone Neoplasms; Chondroblastoma; Chondroma; Diphosphates; Evaluation Studies as Topic; Giant Cell Tumors; Humans; Multiple Myeloma; Osteoma, Osteoid; Radionuclide Imaging; Sarcoma; Strontium Radioisotopes; Technetium; Technetium Tc 99m Pyrophosphate

Topics: Arthritis; Bone Diseases; Bone Neoplasms; Diagnosis, Differential; Diphosphates; Hodgkin Disease; Humans; Multiple Myeloma; Neoplasm Metastasis; Osteitis Deformans; Osteoarthritis; Osteolysis; Osteomalacia; Osteoporosis; Radionuclide Imaging; Reflex Sympathetic Dystrophy; Rheumatic Diseases; Technetium; Tin