Thrombopoietin Improves Stem Cell Mobilization

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Oncology NEWS InternationalOncology NEWS International Vol 8 No 2
Volume 8
Issue 2

SAN FRANCISCO-Recombinant 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 secondary objectives.

SAN FRANCISCO—Recombinant 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 secondary objectives.

“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 Francisco (UCSF).

Patients eligible for the phase II study were adults undergoing autologous peripheral blood stem cell transplant for breast cancer, lymphoma, Hodgkin’s 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 received placebo.

“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.

Enhanced Collection

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 arm—the split-dose regimen.

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