Results of a multi-institutional clinical trial that included a UC San Francisco researcher indicate that use of an experimental drug known as TPO increases the number of people who are medically eligible for autologous stem cell transplantation, a procedure used to replenish the blood cells of cancer patients following high dose chemotherapy.
The trial demonstrated that the recombinant, or genetically engineered, drug, called platelet growth factor thrombopoetin, is effective in stimulating stem cells --the body's primitive bone marrow cells and the ultimate source of all blood cells-- to migrate out of the bone marrow and into the bloodstream. There, they can be collected and stored for safekeeping while patients undergo chemotherapy, which kills both healthy and cancerous cells. The stem cells can then be transplanted back into the patients, providing a fresh supply of healthy blood cells and restoring bone marrow function.
Traditionally, another growth factor, G-CSF, has been relied upon to stimulate stem cell migration into the bloodstream. However, the drug often is unable to stimulate a sufficient number of cells to migrate into the blood. In these cases, patients are unable to receive the extremely intensive regimens of chemotherapy that they need.
The findings, which will be presented at the American Society of Hematology meeting in Miami on Monday, Dec. 7, indicate that TPO helps mobilize stem cells for collection when used in conjunction with G-CSF, according to the lead author of the study, Charles Linker, MD, a clinical professor of medicine and director of the UCSF-Stanford Health Care Adult Leukemia and Bone Marrow Transplant Program at UCSF.
The current phase II clinical trial, conducted in 134 patients, established that TPO, administered in conjunction with G-CSF, significantly boosts the odds of stem cells migrating into the bloodstream in sufficient numbers to stimulate re-growth of blood cells.
The majority of patients in the study had breast cancer; others had lymphoma or related cancers. All patients received G-CSF, and some received TPO as well. Of the group receiving both drugs, 94 percent achieved the minimum number of stem cells needed to make transplantation an option. In contrast, 75 percent of those patients receiving only G-CSF did.
Likewise, 76 percent of the patients who received both growth factors achieved the optimal number of stem cells for permitting rapid re-growth of blood cells after transplantation, as opposed to 46 percent of those receiving just G-CSF. (Patients who receive an adequate but not optimal stem cell dose have longer recovery times and a greater need for transfusions.)
In the patient population evaluated, said Linker, no neutralizing antibodies to TPO have been observed. In the study, TPO was well tolerated and caused no serious side effects.
In addition to Linker, co-authors of the study included researchers at University of Texas--MD Anderson Cancer Center; University of Louisville-Brown Cancer Center; City of Hope National Medical Center; University of South Carolina-Center for Cancer Treatment and Research; Baylor University; West Virginia University; Fred Hutchinson Cancer Research Center; Washington University and Response Oncology, Inc.
The study was funded by Pharmacia & Upjohn and Genentech, Inc.