Melphalan-mobilized blood stem cell components contain minimal clonotypic myeloma cell contamination.
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.
Zhou
Ping
P
Department of Medicine, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Zhang
Yana
Y
Martinez
Carmen
C
Kalakonda
Nagesh
N
Nimer
Stephen D
SD
Comenzo
Raymond L
RL
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
D009194:Myeloma Proteins; D016179:Granulocyte Colony-Stimulating Factor; D008558:Melphalan