Ex vivo pharmacological purging of leukapheresis collections with nitrogen mustard: amifostine pretreatment improves both early and late peripheral blood progenitor cell recovery.
Ex vivo pharmacological purging of bone marrow has been used to eliminate clonogenic tumor cells contaminating the autograft and potentially responsible of relapse. A considerable improvement of pharmacological purging would be achieved only if normal marrow progenitor cells could be selectively protected by the cytotoxicity of these agents. Amifostine (WR-2721; Ethyol), a phosphorylated aminothiol compound, has been shown to have this property both in vivo and in vitro. We describe here, an experimental model for ex vivo purging of peripheral blood progenitor cell (PBPC) collections based on the combination of 3 mg/ml of amifostine and the alkylating agent nitrogen mustard. Amifostine pretreatment resulted in a statistically significant protection of normal late and early progenitor cells. Under the same experimental conditions, we observed a 4-6 log reduction of contaminating leukemic cells (i.e., K-562 and CEM) and in contrast to the protection of normal peripheral blood progenitor cells, preincubation of contaminating K-562 or CEM with amifostine did not significantly alter the LD95 nitrogen mustard concentration. Moreover, when we tested fresh human leukemia progenitor cells, amifostine pretreatment sensitized the leukemic cells to the cytotoxic effects of NM.
Poloni
A
A
Clinic of Hematology, University of Ancona, Torrette di Ancona, Italy. clinemat@popcsi.unian.it
Leoni
P
P
Curzi
L
L
Cantori
I
I
Mancini
S
S
Montanari
M
M
Masia
M C
MC
Olivieri
A
A
D004999:Amifostine / Q000627:therapeutic use*; D000818:Animals; D016465:Bone Marrow Purging / Q000379:methods*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology / Q000628:therapy*; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology / Q000628:therapy*; D008466:Mechlorethamine; D051379:Mice
D008466:Mechlorethamine; D004999:Amifostine