A new drug may help cancer patients mobilize the cells necessary torestore their blood-forming system after high-dose chemotherapy,according to results from a clinical trial at the Kimmel Cancer Centerat Thomas Jefferson University Hospital in Philadelphia and at othercenters across the nation.
In the phase II trial, researchers were attempting to determine ifpatients with multiple myeloma or non-Hodgkin's lymphoma who receivedthe drug AMD-3100 along with the standard drug G-CSF(granulocyte-colony stimulating factor) would have more stem cellsavailable for transplantation.
AMD-3100 blocks a specific cellular receptor, triggering themovement of stem cells out of the bone marrow and into the circulatingblood, boosting the supply of marrow stem cells available fortransplantation. Stem cell transplantation entails collecting certaintypes of cells known as hematopoietic stem cells from patients whoreceive treatment with high-dose radiation and/or chemotherapy forcancers such as leukemias, lymphomas and multiple myeloma, all of whichinvolve the blood and immune system. The cells, once returned to thebody, help restore the blood-forming system within the bone marrow --and the body's immune system, which is severely damaged if notdestroyed by treatment.
Stem cell transplantation is considered "front-line therapyfor multiple myeloma, or cancer of the bone marrow, and for high-riskleukemia and lymphoma patients," says Neal Flomenberg, M.D., professorof medicine and director of medical oncology at Jefferson MedicalCollege of Thomas Jefferson University, who led the trial at Jefferson.
The researchers found that all of the 25 patients (10 patientswith multiple myeloma and 15 patients with non-Hodgkin's lymphoma)given the drug combination could move enough cells from the marrow tothe bloodstream compared to only 64 percent of those who had G-CSFalone. They report their results September 1, 2005 in the journalBlood.
As a result, Dr. Flomenberg says, there were fewer stemcell collections necessary and more stem cells retrieved. The greaterthe number of available stem cells, the more likely transplantationwill be successful. In some cases, this can mean the difference betweena patient being able to receive a transplant or not. The drug haslittle toxicity.
"One of the most important results from the trial was thatnine patients who would not have been able to mobilize stem cells to goto transplant with G-CSF alone could now mobilize them with thecombination of G-CSF and AMD-3100," Dr. Flomenberg says.
In addition, some patients who received AMD-3100 needed fewerstem cell collections to get the necessary number of cells, making theoverall process less taxing. Those who still required the same numberof collections had a higher total of stem cells.
"It's hoped that the drug combination will make white cell andplatelet recovery quicker and allow patients who wouldn't haveotherwise been able to mobilize stem cells for transplant now be ableto do so," he says. Without adequate numbers of stem cells fortransplantation, patients may have a delayed recovery of their immunesystems and be at greater risk of infection.
Most patients undergo standard chemotherapy for four to eightmonths before they have a stem cell transplant, he explains. Somepatients won't have a transplant until their disease relapses andtreatment once again puts them back in remission. These treatmentssometimes make subsequent stem cell collection difficult.
Approximately 25 percent to 35 percent of transplant patients-- and perhaps as many as 65 percent -- have trouble moving optimalnumbers of stem cells from their bone marrow into the bloodstream usingG-CSF. "Some patients with the standard approach don't mobilize well,meaning more collections and often a poor or unusable cell product," hesays.
Dr. Flomenberg believes that the drug combination will become astandard treatment for such cases involving stem cell transplantation."The treatment has potential to alter the standard of practice," hesays.
Researchers currently are conducting two phase III trialscomparing G-CSF and placebo to G-CSF and AMD-3100 in 600 patients witheither non-Hodgkin's lymphoma or multiple myeloma, he notes. Jeffersonis participating in both trials, in addition to another phase II trialwith AMD-3100 alone.
The research is sponsored by AnorMED, Inc., a Vancouver,British Columbia-based drug development company. AnorMED's efforts areaimed at the discovery and development of small molecule therapeuticsto treat diseases including HIV, rheumatoid arthritis, asthma andcancer.
For more information about participating in clinical trials at Jefferson, call 1-800-JEFF-NOW.
Materials provided by Thomas Jefferson University. Note: Content may be edited for style and length.
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