A combination of CD34 selection and complement-mediated immunopurging (anti-CD15 monoclonal antibody) eliminates tumor cells while sparing normal progenitor cells.
Autologous bone marrow transplantation (ABMT) for acute myeloid leukemia (AML) in first complete remission (CR) results in a prolonged disease-free survival (DFS) of 34%-57%. Relapse of the underlying disease is the major cause for failure of ABMT. Relapse can result fom tumor cells either surviving in the patient or reinfused in the autograft. Genetic marking of autografted cells has demonstrated that transplanted cells contribute to relapse. This finding supports the use of purged autografts. Several purging techniques have been used. Immunologic purging using the monoclonal antibody (mAb) PM-81 (anti-CD15) has been used by our center with a long-term DFS in 50% of AML patients. PM-81 reacts with 90% of AML patients, and we have used it for over 10 years. We have investigated a two-stage purging technique involving initial selection for CD34+ cells followed by mAb purging in bone marrow (BM) and peripheral blood stem cell (PBSC) harvests. This method achieved up to a 7 log diminution in leukemic cells and 1-4 log reduction in CD15+ cells, without a significant loss of hematopoietic progenitor cells. This double-purging technique has the advantages of cytoreduction, elimination of CD34- leukemic cells, and possible improvement in the clinical efficacy of purging by concentrating for CD34+ cells. Cytoreduction by CD34 enrichment followed by purging may facilitate the use of PBSC transplants in AML.
Nimgaonkar
M
M
Department of Medicine, University of Pittsburgh Medical Center, PA 15213, USA.
Kemp
A
A
Lancia
J
J
Ball
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D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018952:Antigens, CD34 / Q000032:analysis*; D000951:Antigens, Neoplasm / Q000276:immunology*; D016465:Bone Marrow Purging / Q000379:methods*; D016026:Bone Marrow Transplantation; D002469:Cell Separation / Q000379:methods; D003165:Complement System Proteins / Q000502:physiology*; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D007951:Leukemia, Myeloid / Q000628:therapy; D016256:Lewis X Antigen / Q000276:immunology*; D012016:Reference Values; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D000951:Antigens, Neoplasm; D016256:Lewis X Antigen; D003165:Complement System Proteins