title: The growth capacity of hematopoietic progenitor cells in severe neutropenia induced by famotidine.
abstract: In four cases of severe neutropenia of unknown origin we found a strong inhibition of the growth of granulocyte-macrophage (GM) progenitor cells. The development of GM colonies in culture (GM-CFU-c) was more than 80% reduced in comparison to the control group. In particular, the interleukin 3-(IL-3) and granulocyte macrophage colony-stimulating factor-(GM-CSF) dependent growth was affected; a combination of growth factors (IL-3, GM-CSF, and G-CSF, the granulocyte colony-stimulating factor) resulted in a less reduced growth. The findings were primarily compatible with drug-induced bone marrow failure. Among the medications given to the patients, famotidine, an H2-receptor blocker, was discussed as an agent which possibly triggers off this process. After the withdrawal of famotidine, in three cases a continual increase of the growth of GM precursors was detected, reaching the normal level 7-17 days later. In one case, further investigations of the progenitor cells could not be carried out due to the death of the patient, but the rapid increase of neutrophils in the peripheral blood after withdrawal of famotidine pointed to the recovery of hematopoiesis. In vitro studies showed that famotidine, depending on the dose, inhibits the single growth factor-dependent colony growth (IL-3, GM-CSF, or G-CSF) of bone marrow progenitors from a concentration as low as 10 micrograms/ml. With the combination of all three growth factors only slight inhibitory effects were detectable (up to 150 micrograms/ml famotidine). These results indicate that famotidine, in common with other H2-receptor antagonists, can affect hematopoietic progenitor cells. However, the plasma concentration of famotidine normally used in ulcer therapy does not seem to influence the hematopoiesis. Apparently, the progenitor cells of only a few patients possess a higher sensitivity to the blockade of H2-receptors at this concentration of famotidine. This was demonstrated in one case (patient 3) 2 years after the patient had recovered from famotidine-induced neutropenia. The growth of peripheral myeloid, erythroid, and multilineage progenitor cells of this patient was remarkably reduced even at famotidine concentrations of 0.1-5.0 micron/ml whereas in the control group no inhibition was detected at these famotidine concentrations. Again, the IL-3-dependent colony formation was more affected than in the case of the combination of IL-3, GM-CSF, and G-CSF. After the removal of accessory cells the inhibitory effect of famotidine persisted, demonstrating that accessory cells do not play a major role in this process.
authors.affiliation: Medizinische Universitätsklinik, Abteilung Hämatologie/Onkologie, Göttingen, Federal Republic of Germany.
authors.forename: T
authors.initials: T
authors.lastname: Liersch
authors.forename: J H
authors.initials: JH
authors.lastname: Beyer
authors.forename: G
authors.initials: G
authors.lastname: Krieger
authors.forename: K
authors.initials: K
authors.lastname: Vehmeyer
mesh_terms: D000328:Adult; D001853:Bone Marrow / Q000473:pathology*; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D015738:Famotidine / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D007970:Leukopenia / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011336:Probability; D012016:Reference Values
chemical_list: D015738:Famotidine