High dose chemotherapy followed by peripheral blood hematopoietic stem cell (PBSC) transplantation is frequently used for treating various hematologic malignancies. To facilitate this process, autologous PBSC are typically collected, cryopreserved and stored for some period of time. Current PBSC cryopreservation requires the use of molar concentrations of the cryoprotectant additive dimethyl sulfoxide (DMSO). Typically, frozen-thawed cells are transplanted back into patients along with DMSO. However, reinfusion of DMSO has long been associated with various adverse events, ranging from skin flushing, headache, fever, dyspnea, abdominal cramping, nausea, and diarrhea to more sever effects such as, hemolysis, cardiovascular symptoms and cerebrovascular ischemia leading to neurological events. These can result in increased morbidity, prolonged hospitalization, and increased treatment-related costs. Currently, when removal of DMSO is attempted, the procedures typically involve cell """"""""washing"""""""" using centrifugation. These methods introduce mechanical forces and osmotic stress causing cell packing/clumping and potential significant cell loss. They also require additional laboratory staff as well, and take between 3 and 4 hours of work per patient, which makes the procedure more expensive and practically difficult for many institutions. Finally, it is difficult to kept the cells in a """"""""closed"""""""" system during cell washing, which may lead to contamination. It is the goal of this proposal to finalize, build under appropriate design control and test the automated, portable, closed-system diffusion-driven washing device developed in Phase I for use in clearance of DMSO from PBSC, to prevent infusion of DMSO into patients during clinical transplant without loss of cell numbers or cell functionality. In this Phase II research, the device will be evaluated in preclinical and ultimately clinical testing for 510(k) premarket application to the FDA for clearance to market the device in Phase III. Preclinical testing will rely on in vitro flow cytometry and clonogenic ability as well as engraftment in a NOD/SCID mouse model. Clinical testing will include use in up to 20 multiple myeloma patients, pending acceptable preclinical results.
STATEMENT Peripheral blood stem cell transplant (PBSC) is used to treat many types of diseases, such as lymphoma, leukemia, multiple myeloma, breast cancer, testicular cancer, neuroblastoma and others. These cells are collected, frozen and stored over several periods to ensure enough are available for transplant, and to freeze these cells a compound called dimethyl sulfoxide (DMSO) is added. This DMSO protects the cells during freezing, but can be damaging to cells after they are thawed and can cause complications with transplantation of PBSC. The goal of this research is to produce a device to easily remove DMSO from PBSC before they are transplanted, increasing effectiveness of the cells and reducing potential complications. ? ? ?
