Ex VivoTreatment of Murine Splenocyte-Supplemented Bone Marrow Inocula with Mafosfamide Prior to Allogeneic Transplantation in an Attempt to Prevent Lethal Graft-VERSUS-Host Disease without Compromising Engraftment
作者:
KohnFred R.,
SladekNorman E.,
期刊:
Immunopharmacology and Immunotoxicology
(Taylor Available online 1988)
卷期:
Volume 10,
issue 3
页码: 387-398
ISSN:0892-3973
年代: 1988
DOI:10.3109/08923978809041428
出版商: Taylor&Francis
数据来源: Taylor
摘要:
AbstractMurine splenocyte-supplemented bone marrow cell suspensions were incubated with mafosfamide, an analog of“activated”cyclophosphamide, prior to transplantation across major histocompatibility barriers into lethally-irradiated recipient mice in an attempt to reduce the incidence of graft-versus-host disease (GvHD)-related mortality without compromising engraftment. Irradiated mice that received vehicle-treated splenocyte-supplemented bone marrow inocula developed symptoms of severe GvHD; the majority of such animals did not survive. Treatment of donor cells with 160μM mafosfamide for 30 min resulted in a marked increase in animal survival without evidence of GvHD. Survival of bone marrow allografts was demonstrated by the persistence of donor-type mononuclear cells in the peripheral blood of surviving animals. Treatment of donor cells with a four-fold higher concentration of mafosfamide also resulted in a significant increase in survival without evidence of GvHD; however, host resistance to engraftment was indicated by a low percentage of donor mononuclear cells in the peripheral blood of the survivors. Treatment of donor cells with a four-fold lower concentration of mafosfamide resulted in a slight increase in survival; however, all animals developed symptoms of GvHD. These results indicate that, at appropriate concentrations, mafosfamide can effect the elimination of GvHD-causing T lymphocytes from donor bone marrow inocula without compromising its engraftment potential.
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