Spermine dialdehyde, a novel ex vivo purging agent for both allogenic and autologous bone marrow transplantations.
The use of ex vivo purging agents has shown to be beneficial for both allogeneic and autologous bone marrow transplantations. We have shown previously that spermine dialdehyde (SDA), an oxidized product of spermine, when used in phosphate-buffered saline (PBS) preferentially inhibits T-cell proliferation while sparing myeloid cells. Lethally irradiated mice were rescued by reconstitution with SDA-treated allogeneic marrow and showed no sign of graft-vs-host disease (GVHD). In this paper, we show by HPLC analysis that SDA degraded rapidly in PBS but remained intact in saline. Administered in saline, SDA was more inhibitory on leukemic cell lines than normal myeloid or T-cells. Lethally irradiated mice receiving a syngeneic bone marrow leukemic cell mixture treated ex vivo with SDA in saline did not manifest leukemia. Thus, the preferential inhibitory effect of SDA and its degraded products in different buffers suggest that SDA could act as a novel purging agent for both allogeneic and autologous bone marrow transplantations.
Lau
C
C
Biological Research Department, R. W. Johnson Pharmaceutical Research Institute, Don Mills, Ontario, Canada.
Wang
E
E
Ishaque
A
A
Jones
K
K
Wong
B
B
Kimsto
L
L
Conant
J
J
D000171:Acrolein / Q000032:analysis; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D007942:Leukemia, Experimental / Q000473:pathology; D051379:Mice; D013096:Spermine / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D014407:Tumor Cells, Cultured / Q000187:drug effects
C050864:N,N'-bis(3-propionaldehyde)-1,4-diaminobutane; D013096:Spermine; D000171:Acrolein