Dept Microbiology & Immunology
Inhibiting PGE2 for mobilizing blood stem cells
Autologous transplantation of mobilized peripheral blood is an important treatment modality for patients with Multiple Myeloma and Non-Hodgkin's Lymphoma and the best curative or prolonged disease free option. In a significant majority of these patients an optimal number of stem cells cannot be collected, incurring considerable cost to repeat/extend mobilization or treat post-transplant infectious complications. We have recently identified and published in the journal Nature, that inhibiting COX enzymes responsible for prostaglandin E2 (PGE2) synthesis using non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, significantly enhances the number of blood forming stem cells that can be mobilized to peripheral blood, where they can be collected for use in blood stem cell transplant. In addition, NSAIDs work synergistically in combination with the standard drug Neupogen used clinically to mobilize stem cells for collection and transplant, and provide a stem cell graft that engrafts better and restores blood cell production faster than Neupogen used alone. A cross disciplinary team of cell biologists, pathologists and clinicians at IUSM, Harvard and Vanderbilt cooperated to define the mechanism of action of NSAIDs and we have validated our studies in genetic mouse models, baboons and normal volunteers. We will very soon clinically translate this paradigm shifting research, which differentially targets the niches in bone marrow where stem cells reside, to develop a novel, inexpensive and more efficacious blood stem cell mobilizing regimen. We believe that the use of already FDA approved NSAIDs is a medically sound and fiscally responsible means to enhance stem cell collection in these patients. IRB approval is in hand and the clinical trial will start shortly.