ABSTRACT
Autologous peripheral blood progenitor cell (PBPC) transplantation is the treatment of choice for selected myeloma patients. However, tumor cells contaminating the apheresis product are a potential source of relapse. Here we report a sequential purging strategy targeting mature and immature clonogenic myeloma cell populations in the autograft. Thawed PBPC products of myeloma patients were treated with rituximab to kill CD138(-)20(+) B cells (highly clonogenic immature cells), and bortezomib to target CD138(+) cells (normal and differentiated myeloma plasma cells), followed by coculture with allogeneic mesenchymal stem cells (MSC) from normal donors. After 7 days of coculture, nonadherent cells were removed and cultured in the absence of MSC for an additional 7 days. Then, efficacy of purging (removal of CD138(-)20(+) and CD138(+) cells) was assessed by flow cytometry and PCR. We used our ex vivo purging strategy to treat frozen aphereses from 16 patients. CD138(+) and CD138(-)20(+)(19(+)) cells present in the initial products were depleted more than 3 and 4 logs, respectively based on 10(6) flow-acquisition events, and to levels below the limit of detection by PCR. In contrast, total nucleated cell (TNC), CD34(+) cell, and colony-forming cell numbers were increased by approximately 12 to 20, 8-, and 23-fold, respectively. Overall, ex vivo treatment of apheresis products with rituximab, bortezomib, and coculture with normal donor MSC depleted mature and immature myeloma cells from clinical aphereses while expanding the normal hematopoietic progenitor cell compartment.
Subject(s)
Antibodies, Monoclonal, Murine-Derived/pharmacology , Bone Marrow Purging/methods , Boronic Acids/pharmacology , Hematopoietic Stem Cells/drug effects , Multiple Myeloma/surgery , Peripheral Blood Stem Cell Transplantation/methods , Pyrazines/pharmacology , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antigens, CD34/biosynthesis , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Boronic Acids/administration & dosage , Bortezomib , Cell Line, Tumor , Cell Separation/methods , Hematopoietic Stem Cells/cytology , Hematopoietic Stem Cells/immunology , Humans , Magnetics , Multiple Myeloma/drug therapy , Multiple Myeloma/pathology , Pyrazines/administration & dosage , Rituximab , Transplantation, AutologousABSTRACT
New aesthetic restorative materials claiming superior polish retention have recently been introduced. This study compared polish retention of eight different types of aesthetic restorative materials including ormocer and nanofill composites over a 6-month ageing period in distilled water. Eight specimens of each material were fabricated and roughened with 320 grit grinding paper using a lapping device and finished/polished with a graded abrasive disk system. Mean roughness was then determined using a surface profilometer. The specimens were then stored in distilled water at 37 degrees C and roughness measurements were repeated after 3 and 6 months of ageing. Mean surface roughness values ranged from 0.15 to 0.68 microm for immediate readings and 0.17 to 1.02 microm after ageing for 6 months. With the exception of the highly viscous glass ionomer cement, the surface polish of most materials did not deteriorate much over time. At all time intervals, composite materials based on ormocer and nanomer technology were significantly smoother than all other materials evaluated.