title: Allogeneic stem cell transplantation with peripheral blood stem cells mobilized by pegylated G-CSF.
abstract: Mobilization of stem cells with pegylated granulocyte colony-stimulating factor (peg-G-CSF) modulates donor T- and natural killer T-cell (NKT-cell) functions, thus separating graft-versus-host from graft-versus-leukemia disease in animal models. We report a phase I/II study that analyzed the feasibility of mobilizing stem cells from normal donors with peg-G-CSF and the ability of these cells to restore hematopoiesis in allogeneic transplant recipients after myeloablative conditioning. Administration of 6 mg of peg-G-CSF resulted in suboptimal stem cell mobilization, with a peak peripheral blood CD34+ count of 29+/-5/microL. Apheresis 4 days after peg-G-CSF yielded 2.7+/-.4x10(6) CD34+ cells/kg recipient weight, and all donors required a second collection on day 5 to yield a total of 4.2+/-.5x10(6) CD34+ cells/kg recipient weight. After escalation of the dose to 12 mg, the peak CD34+ count was 99+/-11/microL and 12 of 13 donors collected sufficient stem cells for transplantation in a single apheresis (8.9+/-1.4x10(6) CD34+ cells/kg recipient weight). Late transient increases in serum hepatic transaminases were noted, but other side effects (predominantly bone pain) were otherwise similar to those seen in donors mobilized with standard G-CSF. Median neutrophil and platelet engraftments occurred on days 18 and 14, respectively, after transplantation and were identical to those seen with in recipients of grafts mobilized with standard G-CSF. With a median follow-up of 357 days, the incidence of grade II-IV acute graft-versus-host disease was 50% and there have been no relapses to date. Mobilization of stem cells with peg-G-CSF in normal donors is feasible and 12 mg results in mobilization characteristics similar to those of standard G-CSF.
authors.affiliation: The Queensland Institute of Medical Research, Herston, and Bone Marrow Transplant Unit, Royal Brisbane Hospital, Brisbane, Queensland, Australia. geoffH@qimr.edu.au
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Hill
authors.forename: Edward S
authors.initials: ES
authors.lastname: Morris
authors.forename: Madonna
authors.initials: M
authors.lastname: Fuery
authors.forename: Cheryl
authors.initials: C
authors.lastname: Hutchins
authors.forename: Jason
authors.initials: J
authors.lastname: Butler
authors.forename: Andrew
authors.initials: A
authors.lastname: Grigg
authors.forename: Andrew
authors.initials: A
authors.lastname: Roberts
authors.forename: Ken
authors.initials: K
authors.lastname: Bradstock
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Szer
authors.forename: Glen
authors.initials: G
authors.lastname: Kennedy
authors.forename: James
authors.initials: J
authors.lastname: Morton
authors.forename: Simon
authors.initials: S
authors.lastname: Durrant
mesh_terms: D000328:Adult; D003520:Cyclophosphamide / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007938:Leukemia / Q000145:classification / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D033581:Stem Cell Transplantation / Q000379:methods*; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods; D014916:Whole-Body Irradiation
chemical_list: D007166:Immunosuppressive Agents; C486981:pegylated granulocyte colony-stimulating factor, human; D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols; D003520:Cyclophosphamide