Multiple Myeloma (MM) is a cancer of B cells that can be suppressed for years by treatment with chemotherapy at doses so strong that it kills the blood forming stem cells. In a process known as auto-transplantation (auto-HCT), the blood forming stem cells of MM patients are collected and frozen prior to high-dose chemotherapy. After completion of the chemotherapy, the frozen stem cells are thawed infused, thereby allowing recovery of normal blood production. It has long been known that the infused grafts are contaminated with MM, a finding that is associated with the high rate of relapse after auto-HCT. We also know that for MM patients with identical twin donors, infusion of blood stem cell grafts from the identical twin results in a lower risk of disease recurrence. These observations support the idea that contaminated grafts can cause relapse. Attempts to isolate purified blood stem cells in order to purge MM have thus far not decreased the rate of relapse. We believe this is due to inefficiencies of the purging strategy. We seek to transplant pure, MM-free stem cells with a novel strategy that incorporates recent knowledge about MM. We also seek to use new and highly sensitive genomic technologies to ensure that the stem cells are not contaminated. We will also use new genomic approaches to learn how MM develops by asking when MM specific genetic changes, or mutations, develop. This knowledge may improve our ability to determine who may be at risk for this disease.
Statement of Benefit to California:
Multiple Myeloma (MM) is a cancer of the plasma cell, a type of white blood cell, that can lead to bone fractures, kidney damage, and suppressed blood formation. Approximately 1600 new cases of MM are diagnosed annually in California and nearly 22,000 cases nationally. About one third of patients with MM receive intensive chemotherapy followed by infusion of blood cell grafts that contain the necessary blood forming stem cells but that also include the cancerous MM cells. Although this therapy prolongs survival when compared with other treatments, it does not provide cure, in part because cancerous cells are returned to the patient. Treatment of MM requires years of therapy, results in significant emotional hardship and financial costs for patients, their families, and society. This project utilizes new technologies (many of which that were developed by scientists in California and developed in partnerships between industry and academia) to detect cancer cells and to purify blood forming stem cells free of MM contamination. We aim to initiate a clinical trial, first in California, with the goal of improving the treatment of MM by providing cancer-free stem grafts following intensive chemotherapy. We hope this clinical trial will benefit the many MM patients in California and ultimately improve the well being of thousands of patients worldwide.