title: Changes in erythroid progenitor cell and accessory cell compartments in patients with myelodysplastic syndromes during treatment with all-trans retinoic acid and haemopoietic growth factors.
abstract: Differentiation induction therapy is used in myelodysplastic syndromes (MDS) to improve maturation defects and to restore impaired function of malignant cells. To this end, 18 patients with MDS received either a combination therapy consisting in study 1 of all-trans retinoic acid (ATRA) and granulocyte-colony stimulating factor (G-CSF), or in study 2 of a combination with ATRA, G-CSF, erythropoietin (Epo) and tocopherol. The ANC increased in 19/20 patients in both studies, whereas an increase in haemoglobin concentration, platelet counts or reduction of transfusion requirement was seen in only 8/20 patients, correlating strongly with good BFU-E growth (P < 0.001). To assess the role of accessory cells in the modulation of the haemopoietic response to treatment, we analysed the capacity of peripheral blood monocytes to secrete cytokines (IL-1 beta, IL-6, IL-8, TNF alpha). Secretion of all cytokines was significantly reduced before therapy when compared with healthy controls, but increased during therapy, reaching normal levels for IL-8. These data indicate that a combination therapy with ATRA and cytokines improves impaired cytokine secretion from monocytes and induces a multilineage clinical response in a subgroup of MDS patients characterized by an almost intact erythroid compartment. In contrast, induction of TNF alpha might be responsible for treatment failure.
authors.affiliation: Department of Haematology, University of Frankfurt, Germany.
authors.forename: A B
authors.initials: AB
authors.lastname: Maurer
authors.forename: A
authors.initials: A
authors.lastname: Ganser
authors.forename: G
authors.initials: G
authors.lastname: Seipelt
authors.forename: O G
authors.initials: OG
authors.lastname: Ottmann
authors.forename: U
authors.initials: U
authors.lastname: Mentzel
authors.forename: G R
authors.initials: GR
authors.lastname: Geissler
authors.forename: D
authors.initials: D
authors.lastname: Hoelzer
mesh_terms: D000328:Adult; D000368:Aged; D001772:Blood Cell Count / Q000187:drug effects; D003131:Combined Modality Therapy; D016207:Cytokines / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000187:drug effects* / Q000473:pathology; D004920:Erythropoiesis / Q000187:drug effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D016298:Hematopoietic Cell Growth Factors / Q000627:therapeutic use*; D006801:Humans; D016131:Lymphocyte Subsets / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000276:immunology / Q000628:therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D014212:Tretinoin / Q000627:therapeutic use*; D014810:Vitamin E / Q000627:therapeutic use
chemical_list: D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; D011994:Recombinant Proteins; D014810:Vitamin E; D016179:Granulocyte Colony-Stimulating Factor; D014212:Tretinoin