Short-term myeloid reconstitution following TBI is not adversely affected by doses of FK506 that abrogate lethal GVHD.
Studies were undertaken to determine whether the doses of FK506 that are effective for acute GVHD prophylaxis following lethal irradiation and bone marrow transplantation (BMT) would also suppress myeloid cell reconstitution. FK506 (3 mg/kg/day) abrogated acute lethal graft versus host disease (GVHD) in lethally irradiated C57BL/10SnJ (H-2b) recipient mice given histoincompatible BM plus spleen cells from B10.BR (H-2k) donors and this dose was used in all of the studies. Endogenous and exogenous myeloid repopulation was studied in mice given daily injections of either FK506, an equivalent amount of carrier solvent or no treatment throughout the interval between total body irradiation (TBI) and the day of assay. Repopulation was studied after 400 or 500 cGy TBI (endogenous) and after 950 cGy TBI plus injection with syngeneic BM (exogenous). No consistent adverse effects of FK506 were seen during either exogenous or endogenous recovery. Parameters studied included hematocrit (Hct), WBC count, cells per humerus, spleen weight, splenic colony-forming units, % spleen or BM 59Fe uptake and colony forming cells per humerus. Similarly, when lethally irradiated secondary recipients were reconstituted with BM from FK506 treated primary recipients (lethal irradiation plus exogenous BM), no consistent effects were observed. These data suggest that FK506 given to prevent GVHD would not compromise the myeloid recovery that is critical for survival in the interval of time following shortly after BMT.
Cooper
M H
MH
Department of Surgery, University of Pittsburgh School of Medicine, PA 15261.
Patrene
K D
KD
Vecchini
F
F
Austin
C A
CA
Markus
P M
PM
Boggs
S S
SS
D000818:Animals; D001772:Blood Cell Count; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006410:Hematopoiesis / Q000187:drug effects; D006411:Hematopoiesis, Extramedullary; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006811:Humerus; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D016559:Tacrolimus / Q000494:pharmacology*; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D016559:Tacrolimus