Evaluation of the effect of medroxyprogesterone acetate on bone marrow progenitor cells

Various clinical studies have demonstrated that high-dose medroxyprogesterone acetate (HD-MPA) can reduce hematologic toxicity in patients receiving chemotherapy for advanced solid tumors. The underlying mechanism(s) of this action is still unknown. A direct effect of MPA on hemopoietic cells has be...

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Bibliographic Details
Published inTumori Vol. 77; no. 5; p. 399
Main Authors Pedrazzoli, P, Bacciocchi, G, Da Prada, G A, Preti, P, Pavesi, L, Poggi, G, Locatelli, F, Rosti, V, Robustelli della Cuna, G
Format Journal Article
LanguageEnglish
Published United States 31.10.1991
Subjects
Bone Marrow - drug effects
Cytarabine - antagonists & inhibitors
Hematopoietic Stem Cells - drug effects
Humans
Medroxyprogesterone - analogs & derivatives
Medroxyprogesterone - pharmacology
Medroxyprogesterone Acetate
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Summary:Various clinical studies have demonstrated that high-dose medroxyprogesterone acetate (HD-MPA) can reduce hematologic toxicity in patients receiving chemotherapy for advanced solid tumors. The underlying mechanism(s) of this action is still unknown. A direct effect of MPA on hemopoietic cells has been postulated, but in vitro studies have given contradictory results. To clarify the biologic activity of MPA on hemopoiesis we have evaluated in vitro growth of pluripotent and committed progenitor cells from bone marrow cells which were preincubated in vitro with various doses of MPA and subsequently treated with or without the S-phase-specific drug arabinoside-cytosine (Ara-C). Four healthy subjects and 8 patients with advanced stage solid tumors with no bone marrow involvement were studied. In our experimental model we did not observe any effect of MPA on Ara-C killing of progenitor cells from either bone marrow mononuclear cells or bone marrow mononuclear cells depleted of T-lymphocytes and adherent cells. These results suggest that MPA does not act directly (or indirectly through the production of cytokines by T-lymphocytes and/or monocytes and macrophages) on bone marrow progenitors. In addition, the supposed mechanism of rendering stem cells less susceptible to the insult of cytotoxic drugs by lowering the number of progenitors in the S-phase has been ruled out by cell kinetic studies.
ISSN:0300-8916
DOI:10.1177/030089169107700507