SAN FRANCISCORecombinant human thrombopoietin (TPO) plus
G-CSF (Neupogen) helps mobilize stem cells for collection better than
G-CSF alone, Charles Linker, MD, said at the Fortieth Annual Meeting
of the American Society of Hematology (ASH). In addition to showing
efficacy in stem cell mobilization, the trial had a number of
We wanted to explore different TPO schedules; determine if the
addition of TPO would accelerate platelet recovery and reduce the
need for platelet transfusion; and determine if GM-CSF was more
effective than G-CSF when combined with TPO as has been suggested in
the models, said Dr. Linker, director of the Adult Leukemia and
Bone Marrow Transplant Program at the University of California, San
Patients eligible for the phase II study were adults undergoing
autologous peripheral blood stem cell transplant for breast cancer,
lymphoma, Hodgkins disease, or myeloma. Of 134 randomized
patients, the largest group (87%) were women with breast cancer who
had not received extensive prior therapy.
Patients were randomized into five treatment groups: Group 1 received
TPO 1.5 µg/kg IV on mobilization day 5; group 2 received the
same dose on day 1; groups 3 and 4 received the same total dose, but
the dose was split over mobilization days 1, 3, and 5; group 5
Therefore, we had a late TPO group, an early TPO group, a
split-dose TPO group, and a placebo group, Dr. Linker said.
During mobilization, all groups received a G-CSF dose of 10
µg/kg/day beginning on day 5.
Leukophereses began on day 9 and continued until a target graft of 5
× 106 CD34+ cells/kg or greater was collected or
until a maximum of six phereses had been done. Or if the
phereses appeared to be futile, defined as two consecutive
collections with very low CD34 cell counts, Dr. Linker added.
During the reconstitution phase (post-transplant), all the groups,
except group 4, received G-CSF (5 µg/kg/day); group 4 received
GM-CSF (250 µg/m²/day). TPO was given to groups 1 through 4
(1.5 µg/kg IV) on reconstitution days 0, 2, 4, and 6. Group 5
continued to receive a placebo.
Of the 129 patients who received TPO and underwent one or more
phereses, 115 achieved the minimum graft volume, and 112 received
high-dose chemotherapy and transplant, with TPO given post-transplant.
The results showed a significant enhancement of CD34 cell collection
in the groups receiving TPO. The most benefit was seen in the early
TPO group (group 2), with 70% of patients achieving the target graft,
and in the split-dose group (groups 3 and 4), with 79% of patients
reaching the target. In group 1 (late TPO), 67% of patients reached
the target, and in the placebo group, only 46%.
The percentage of patients achieving the minimum graft was also
significantly greater with TPO: 96% in group 2; 94% in groups 3 and
4; 85% in group 1; and 75% in the placebo group.
The number of cells harvested in each pheresis was higher with TPO
use: The average collection in groups 3 and 4 was 3.1 CD34+ cells
× 106/kg; in group 2, the average collection was
2.67; in group 1, it was 1.86; and in the placebo group, 1.65.
The TPO groups required fewer phereses to collect the target graft:
three in group 1; two in groups 2, 3, and 4; and four in the placebo group.
In contrast to these positive results, there was no effect on
platelet reconstitution after transplant, Dr. Linker said.
Neutrophil recovery was rapid and similar in all groups.
Dr. Linker pointed out that there did seem to be a
statistically significant, but probably clinically insignificant
delay in neutrophil recovery in patients receiving GM-CSF in place of G-CSF.
Based on this data, he said, a phase III trial will be done using the
most effective TPO armthe split-dose regimen.