Ex vivo purging with NK-92 prior to autografting for chronic myelogenous leukemia.
Although controversial, purging of the autograft may be necessary to optimize transplant outcome, especially if better treatments become available to eliminate or control residual disease that may be left after the conditioning regimen. The intent of this study was to show that immunological purging with the cytotoxic cell line NK-92 effectively reduces the number of clonogenic cells and that the method can be performed in compliance with GMP. Owing to the easy quantification of bcr-abl transcripts, chronic myelogenous leukemia (CML) was used as a model disease for proof of principle. A detection level of 10(-7) bcr-abl+ cells and purging efficiency of four logs were achievable for the bcr-abl+ cell line, K562. Leukapheresis products collected from CML patients after stem cell mobilization were then tested. For all patients tested, residual CML cells were highly sensitive to purging by NK-92 with a purging efficacy of several logs. No adverse effect on hematopoietic progenitor cell function was noted. These results demonstrate the efficacy of NK-92 as a purging agent to decrease or eliminate malignant contamination of autologous stem cell grafts and establish proof of principle for ex vivo purging of CML autografts using cytotoxic effector cells.
Maki
G
G
Bone Marrow Transplant and Cell Therapy, Rush Presbyterian-St Luke's Medical Center, Chicago 60612, USA.
Tam
Y K
YK
Berkahn
L
L
Klingemann
H-G
HG
D018952:Antigens, CD34 / Q000378:metabolism; D001483:Base Sequence; D016465:Bone Marrow Purging / Q000379:methods*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004273:DNA, Neoplasm / Q000235:genetics; D016313:Genes, abl; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D066298:In Vitro Techniques; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D007937:Leukapheresis; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000628:therapy*; D014182:Transplantation, Autologous; D014410:Tumor Stem Cell Assay
D018952:Antigens, CD34; D004273:DNA, Neoplasm