An effective immunomagnetic method for bone marrow purging in T cell malignancies.
An immunomagnetic method was developed to purge human bone marrow of malignant T cells, for use in conjunction with autologous bone marrow transplantation in patients with acute lymphoblastic leukemia and lymphoma. Three monoclonal antibodies anti CD2 (BH1), CD5 (BB8) and CD7 (BF12) were used. In model experiments employing MOLT4 cells it was found that with 50-fold excess of immunobeads relative to antigen-positive cells, the use of each antibody alone resulted in a 3.3-3.6 log tumor cell depletion, as assessed in a sensitive and reproducible clonogenic soft agar assay. When all three antibodies were used in a mixture, a purging efficacy of 5 logs was achieved. Two treatment cycles improved these figures to about 4 logs and more than 5 logs. When MOLT4 cells were mixed 1:10 with fresh bone marrow cells the antibody mixture yielded 3.1 and more than 5 log tumor cell depletion with one and two treatment cycles, respectively. This procedure resulted in only an insignificant reduction of the number of CFU-GM and CFU-GEMM progenitor cells. In two patients autotransplanted with purged marrow, the loss of CFU-GM was 37% and 48%, and no tumor cells could be detected by immunocytochemistry after purging. Rapid and sustained engraftment was achieved and both patients remain in complete remission after more than 20 months.
Wang
M Y
MY
Norwegian Radium Hospital, Montebello, Oslo.
Kvalheim
G
G
Kvaløy
S
S
Beiske
K
K
Jakobsen
E
E
Wijdenes
J
J
Pihl
A
A
Fodstad
O
O
D000911:Antibodies, Monoclonal; D016465:Bone Marrow Purging / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D007158:Immunologic Techniques; D015458:Leukemia, T-Cell / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D008280:Magnetics; D014407:Tumor Cells, Cultured / Q000473:pathology
D000911:Antibodies, Monoclonal