Comparative effects of amifostine (Ethyol) on normal hematopoietic stem cells versus human leukemic cells during ex vivo purging in autologous bone marrow transplants.
The protective action of amifostine (Ethyol, US Bioscience, Inc. West Conshohocken, PA) against the toxic effects of cyclophosphamide derivatives on the normal progenitor/stem cell pool was investigated. Early and late normal progenitor/stem cells were studied in the presence of placenta-conditioned medium (placenta-conditioned medium-granulocyte-macrophage colony-forming units); in the presence of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin-3, erythropoietin, stem cell factor (5R-CFU-GM); stimulated granulocyte-macrophage colony-forming and in a long-term culture-initiating cell assay. The preservation of an antileukemic effect was investigated by growing leukemic progenitor cells in the presence of phytohemagglutinin and leukocyte feeder layer with or without 25u interleukin-2. In 10 of 13 cases, a statistically significant (P < .05) protective effect was found on PCM-granulocyte-macrophage colony-forming units, in four of 10 cases on factor-stimulated granulocyte-macrophage colony-forming units, and in two of six cases on long-term culture-initiating cell. In contrast, amifostine exhibited no protective effect (none of nine cases) on leukemic progenitor cells. From the experimental data, it seems that amifostine is able to protect human normal progenitor/stem cells from cyclophosphamide derivative toxicity, while preserving their antileukemic effects. The therapeutic usefulness of such protection in autologous bone marrow transplantation with purged marrow is obvious.
Douay
L
L
Cell Culture Laboratory, CHU Saint-Antoine, Paris, France.
Hu
C
C
Giarratana
M C
MC
Gorin
N C
NC
D004999:Amifostine / Q000627:therapeutic use*; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D003520:Cyclophosphamide / Q000627:therapeutic use; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000276:immunology*; D013234:Stem Cells / Q000187:drug effects
D003470:Culture Media; D003520:Cyclophosphamide; D004999:Amifostine