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Engraftment of Primates with G-CSF Mobilized Peripheral Blood CD34⁺ Progenitor Cells Expanded in G-CSF, SCF and MGDF Decreases the Duration and Severity of Neutropenia

^a Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA;
^b Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA;
^c Amgen, Inc., Thousand Oaks, California, USA;
^d University of Washington Regional Primate Research Center, Seattle, Washington, USA, and
^e Bone Marrow Transplant Program, University of Colorado Health Science Center, Denver, Colorado, USA

Key Words. CD34 • Expansion • Hematopoietic progenitors • MGDF • SCF • Transplantation

Dr. Robert G. Andrews, Pediatric Oncology Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., P.O. Box 19024, Seattle, Washington 98109-1024, USA.

We used a primate model of autologous peripheral blood progenitor cell (PBPC) transplantation to study the effect of in vitro expansion on committed progenitor cell engraftment and marrow recovery after transplantation. Four groups of baboons were transplanted with enriched autologous CD34⁺ PBPC collected by apheresis after five days of G-CSF administration (100 µg/kg/day). Groups I and III were transplanted with cryopreserved CD34⁺ PBPC and Groups II and IV were transplanted with CD34⁺ PBPC that had been cultured for 10 days in Amgen-defined (serum free) medium and stimulated with G-CSF, megakaryocyte growth and development factor (MGDF), and stem cell factor each at 100 g/ml. Group III and IV animals were administered G-CSF (100 µg/kg/day) and MGDF (25 µg/kg/day) after transplant, while animals in Groups I and II were not. For the cultured CD34⁺ PBPC from groups II and IV, the total cell numbers expanded 14.4 ± 8.3 and 4.0 ± 0.7-fold, respectively, and CFU-GM expanded 7.2 ± 0.3 and 8.0 ± 0.4-fold, respectively. All animals engrafted. If no growth factor support was given after transplant (Groups II and I), the recovery of WBC and platelet production after transplant was prolonged if cells had been cultured prior to transplant (Group II). Administration of post-transplant G-CSF and MGDF shortened the period of neutropenia (ANC < 500/µL) from 13 ± 4 (Group I) to 10 ± 4 (Group III) days for animals transplanted with non-expanded CD34⁺ PBPC. For animals transplanted with ex vivo-expanded CD34⁺ PBPC, post-transplant administration of G-CSF and MGDF shortened the duration of neutropenia from 14 ± 2 (Group II) to 3 ± 4 (Group IV) days. Recovery of platelet production was slower in all animals transplanted with expanded CD34⁺ PBPC regardless of post-transplant growth factor administration. Progenitor cells generated in vitro can contribute to early engraftment and mitigate neutropenia when growth factor support is administered post-transplant. Thrombocytopenia was not decreased despite evidence of expansion of megakaryocytes in cultured CD34⁺ populations. Stem Cells 1999;17:210-218