ASHBreast cancer transplant patients who received stem cell factor (SCF) combined with G-CSF (Neupogen) for stem cell mobilization produced significantly more stem cells with fewer aphereses than those who received G-CSF alone, Elizabeth Shpall, MD, of the University of Colorado, Denver, said in her presentation at the American Society of Hematology meeting in San Diego.
In this multicenter randomized phase III study in 203 patients with high-risk breast cancer (175 evaluable for primary endpoints), those receiving SCF (20 µg/kg/d) plus G-CSF (10 µg/kg/d) required a median of two fewer aphereses to reach a target yield of 5 million CD34+ cells/kg, compared with patients receiving G-CSF alone. (CD34+ cells are used as a surrogate marker for stem cell content.) Two thirds (67%) of those receiving the combination reached the target yield versus less than half (48%) of those getting G-CSF alone, Dr. Shpall said.
Patients who achieved the 5 million yield target were more likely to engraft platelets (up to 20,000), she said. For those who received between 1 and 2 million CD34+ cells/kg, 25% failed to engraft platelets by day 14 and 13% by day 28. In the 2 to 5 million group, 13% failed to engraft by day 14 and 5% by day 28. Finally, in the group who got the optimal number of CD34+ cells, only one patient (1%) failed to engraft by day 14 and none failed beyond 28 days, she said.
All patients were premedicated to avoid allergic reactions, and the treatment was well tolerated. There were five adverse reactions on the study; two were not predicted (hypoxia, skin desquamation). The other three were allergic-like reactions that resolved with administration of steroids and cessation of SCF.
In future, Dr. Shpall said, SCF plus G-CSF in hematopoietic cell therapy will have substantial impact on apheresis-related morbidity and cost.
In another presentation, Patrick Stiff, MD, of Loyola University, Chicago, described a multicenter randomized phase II study of SCF in 102 heavily pretreated patients with non-Hodgkins lymphoma or Hodgkins disease undergoing high-dose therapy with stem cell support.
Those receiving SCF plus G-CSF had significant improvement in mobilization, with a median of 3.5 million CD34+ cells/kg collected, compared with a median of 2.7 million CD34+ cells/kg for patients receiving G-CSF alone.
A significantly higher proportion of the combination patients reached the target of 5 million or more CD34+ cells/kg, and required significantly fewer aphereses to meet the target, he said. In the G-CSF alone group, 26% failed to reach the minimum collection of 1 million or more, compared with 15% of those mobilized with the combination.
Adverse effects with SCF were primarily injection site reactions that did not require additional treatment, Dr. Stiff said. Systemic allergic-like reactions occurred in 5% of patients, similar to that seen in the breast cancer trial, he said, and these were successfully treated with antihistamines and/or steroids.
An economic analysis of data from Dr. Shpalls breast cancer study showed a total cost savings of $3,915 per patient with the use of SCF plus G-CSF over G-CSF alone in the fist 30 days post-transplant.
In his poster presentation, John Glaspy, MD, of the University of California, Los Angeles, said that the cost savings derived from the more rapid engraftment and fewer collection procedures and transfusion requirements seen in the SCF plus G-CSF patients.
Amgen filed a new drug application for SCF (Stemgen) with the FDA last year for use to improve mobilization of progenitor cells before peripheral blood progenitor cell transplants in cancer patients. The agent is also in phase I/II trials for the treatment of aplastic anemia.