Autologous transplantation of an immunomagnetic bead purged marrow in patients with relapsed acute lymphoblastic leukemia.
In acute lymphoblastic leukemia (ALL) the expected duration of a second complete remission (CR) following conventional aggressive multi-drug treatment is rather short, and long-term survival is rarely seen. Myeloablative consolidation treatment with ABMT in second CR is thought to benefit "high risk" patients thus allowing the escalation of cytoreductive treatment into a lethal range. In three patients with relapsed ALL bone marrow was collected in the very early second remission phase. The autografts were incubated with a panel of monoclonal antibodies bound to magnetobeads (DYNABEADS M450). The pretransplant regimen consisted of total body irradiation (TBI) (14.4 Gy) and cyclophosphamide (CY) (50 mg/kg b.w. x4). Following autologous transplantation of those immunomagnetobead purged marrow grafts, complete hematologic reconstitution was seen in all three patients. They are alive and disease-free for +26, +24 and +17 months post transplant, which is also proven by the absence of detectable gene rearrangements after transplantation. In two of them disease-free survival exceeds the duration of the preceding remission y 20 and 12 months respectively, which is a definitive parameter for therapy effectiveness. Therefore, "high dose" consolidation treatment in very early second CR followed by autologous transplantation of purged bone marrow seems to allow long-term disease-free survival. The technique of ex vivo immunomagnetic bead purging, i.e. the "direct" and "indirect" method of binding monoclonal antibodies to magnetobeads is described.
Körbling
M
M
Department of Internal Medicine V, Heidelberg University, Germany.
Knauf
W
W
Funderud
S
S
Kvalheim
G
G
Hunstein
W
W
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D002469:Cell Separation / Q000379:methods*; D003131:Combined Modality Therapy; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006085:Graft Survival; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D008280:Magnetics; D008863:Microspheres; D009364:Neoplasm Recurrence, Local / Q000601:surgery; D014411:Neoplastic Stem Cells / Q000276:immunology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000473:pathology / Q000601:surgery*; D012074:Remission Induction; D014182:Transplantation, Autologous
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D006684:HLA-DR Antigens