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Blood, Vol. 93 No. 9 (May 1), 1999:
pp. 2798-2806
Recombinant Human Thrombopoietin in Combination With Granulocyte
Colony-Stimulating Factor Enhances Mobilization of Peripheral Blood
Progenitor Cells, Increases Peripheral Blood Platelet Concentration,
and Accelerates Hematopoietic Recovery Following High-Dose Chemotherapy
George Somlo,
Irena Sniecinski,
Anna ter Veer,
Jeffrey Longmate,
Gaylord Knutson,
Stanimir Vuk-Pavlovic,
Ravi Bhatia,
Warren Chow,
Lucille Leong,
Robert Morgan,
Kim Margolin,
James Raschko,
Stephen Shibata,
Merry Tetef,
Yun Yen,
Stephen Forman,
Dennie Jones,
Mark Ashby,
Gwen Fyfe,
Susan Hellmann, and
James H. Doroshow
From the Departments of Medical Oncology and Therapeutics
Research, Transfusion Medicine, and Biostatistics, City of Hope
National Medical Center, Duarte, CA; Stem Cell Laboratory, Mayo Clinic
Cancer Center, Rochester, MN; and Genentech Inc, South San Francisco,
CA.
Lineage-specific growth factors mobilize peripheral blood progenitor
cells (PBPC) and accelerate hematopoietic recovery after high-dose
chemotherapy. Recombinant human thrombopoietin (rhTPO) may further
increase the progenitor-cell content and regenerating potential of PBPC
products. We evaluated the safety and activity of rhTPO as a PBPC
mobilizer in combination with granulocyte colony-stimulating factor
(G-CSF) in 29 breast cancer patients treated with high-dose chemotherapy followed by PBPC reinfusion. Initially, patients received
escalating single doses of rhTPO intravenously (IV) at 0.6, 1.2, or 2.4 µg/kg, on day 1. Subsequent patients received rhTPO 0.6 or 0.3 µg/kg on days  3, 1, and 1, or 0.6 µg/kg on days 1 and 1. G-CSF, 5 µg/kg IV or subcutaneously (SC) twice daily, was started on
day 3 and continued through aphereses. Twenty comparable, concurrently
and identically treated patients (who were eligible and would have been
treated on protocol but for the lack of study opening) mobilized with
G-CSF alone served as comparisons. CD34+ cell yields were
substantially higher with the first apheresis following rhTPO and G-CSF
versus G-CSF alone: 4.1 × 106/kg (range, 1.3 to 17.6)
versus 0.8 × 106/ kg (range, 0.3 to 4.2), P = .0003. The targeted minimum yield of 3 × 106
CD34+ cells/kg was procured following a single apheresis
procedure in 61% of the rhTPO and G-CSF-mobilized group versus 10%
of G-CSF-mobilized patients (P = .001). In rhTPO
and G-CSF mobilized patients, granulocyte (day 8 v 9, P
= .0001) and platelet recovery (day 9 v 10, P
= .07) were accelerated, and fewer erythrocyte (3 v 4, P = .02) and platelet (4 v 5, P = .02)
transfusions were needed compared with G-CSF-mobilized patients.
Peripheral blood platelet counts, following rhTPO and G-CSF, were
increased by greater than 100% and the platelet content of PBPC
products by 60% to 110% on the first and second days of aphereses
(P < .0001) with the greatest effect seen with repeated
dosing of rhTPO at 0.6 µg/kg. rhTPO is safe and well tolerated as a
mobilizing agent before PBPC collection. Mobilization with rhTPO and
G-CSF, in comparison to a comparable, nonrandomized G-CSF-mobilized
group of patients, decreases the number of apheresis procedures
required, may accelerate hematopoietic recovery, and may reduce the
number of transfusions required following high-dose chemotherapy for
breast cancer.
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