title: Treatment with plerixafor in non-Hodgkin's lymphoma and multiple myeloma patients to increase the number of peripheral blood stem cells when given a mobilizing regimen of G-CSF: implications for the heavily pretreated patient.
abstract: We investigated the efficacy and toxicity of combining granulocyte-colony stimulating factor (G-CSF) at standard doses with plerixafor, a CXCR4 inhibitor, to mobilize stem cells in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Patients with NHL and MM underwent mobilization with G-CSF (10 microg/kg/day) for up to 9 days and plerixafor (240 microg/kg/day), which started on the evening of day 4. Apheresis began on day 5 and continued daily until either >or= 5 x 10(6) CD34/kg were collected or to a maximum of 5 aphereses. Toxicities, increase in circulating CD34 cells/microL before and after the first dose of plerixafor, percentage of patients collecting >or= 5 x 10(6) CD34/kg, total CD34 cells/kg collected, engraftment, and exploratory efficacy analyses in heavily pretreated patients were examined. Six sites enrolled 49 patients (NHL, 23; MM, 26). All completed mobilization and 47 of 49 (96%) underwent transplant. Circulating CD34 cells/microL increased by 2.5-fold (1.3-6.0-fold) after the first plerixafor dose. The median CD34 cells/kg collected was 5.9 x 10(6) (1.5-22.5) in 2 (1-5) days of aphereses. Median days to neutrophil and platelet engraftment were 11 (8-16) and 14.5 (7-39) days, respectively. Adverse events primarily were mild nausea and diarrhea (n=24). Twenty-eight (57%) were identified as heavily pretreated patients. Their median fold increase in circulating CD34 cells/microL was 2.5 (1.4-5.0) after plerixafor, similar to minimally pretreated patients. Plerixafor and G-CSF increased circulating CD34 cells/microL and led to the adequate collection of stem cells for autotransplant in 96% of the patients. This combination may have particular value in heavily pretreated patients.
authors.affiliation: BMT Program, Loyola University Stritch School of Medicine, Maywood, Illinois, USA. pstiff@lumc.edu
authors.forename: Patrick
authors.initials: P
authors.lastname: Stiff
authors.forename: Ivana
authors.initials: I
authors.lastname: Micallef
authors.forename: Philip
authors.initials: P
authors.lastname: McCarthy
authors.forename: Margarida
authors.initials: M
authors.lastname: Magalhaes-Silverman
authors.forename: Daniel
authors.initials: D
authors.lastname: Weisdorf
authors.forename: Mary
authors.initials: M
authors.lastname: Territo
authors.forename: Karin
authors.initials: K
authors.lastname: Badel
authors.forename: Gary
authors.initials: G
authors.lastname: Calandra
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34; D001596:Benzylamines; D001781:Blood Component Removal; D002452:Cell Count; D000080027:Cyclams; D004359:Drug Therapy, Combination; D005260:Female; D006085:Graft Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods* / Q000592:standards; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006571:Heterocyclic Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors
chemical_list: D018952:Antigens, CD34; D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor