title: Melphalan-mobilized blood stem cell components contain minimal clonotypic myeloma cell contamination.
abstract: Optimal methods of stem cell mobilization in multiple myeloma are undefined, and contaminating clonotypic cells could contribute to disease recurrence. A phase 2 trial of intravenous melphalan (60 mg/m2) and granulocyte colony-stimulating factor (G-CSF) (10 microg/kg/d) for mobilization was performed. To enhance reliability, contamination was assessed with 2 sensitive methods, immunoglobulin light and heavy chain variable region patient-specific limiting-dilution polymerase chain reaction (PCR). We evaluated 29 stem cell components (SCCs) from 15 patients; for 9 SCCs, only VL PCR was used because of light chain disease or technical problems with VH primers. For 20 SCCs, VL and VH PCR results were highly correlated (r2 = 0.93, P <.01), with 35% (7 of 20) having identical estimates. VH PCR gave significantly higher estimates for 8-and VL PCR for 5-SCCs, supporting the utility of using 2 methods. Estimated clonotypic contamination per SCC was 0.0009% (range, 0%-0.1%) or 0.5 x 10(4) clonotypic cells per kilogram (range, 0-41.2 x 10(4)/kg), and contamination correlated with CD34+ cells collected (r2 = 0.42, P <.01). Melphalan-mobilized SCCs contain minimal clonotypic contamination.
authors.affiliation: Department of Medicine, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.forename: Yana
authors.initials: Y
authors.lastname: Zhang
authors.forename: Carmen
authors.initials: C
authors.lastname: Martinez
authors.forename: Nagesh
authors.initials: N
authors.lastname: Kalakonda
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Nimer
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Comenzo
mesh_terms: D000328:Adult; D000368:Aged; D002999:Clone Cells / Q000473:pathology; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007937:Leukapheresis; D008297:Male; D008558:Melphalan / Q000494:pharmacology*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000628:therapy; D009194:Myeloma Proteins / Q000235:genetics; D009360:Neoplastic Cells, Circulating; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D027041:Somatic Hypermutation, Immunoglobulin
chemical_list: D009194:Myeloma Proteins; D016179:Granulocyte Colony-Stimulating Factor; D008558:Melphalan