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.
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.
Maurer
A B
AB
Department of Haematology, University of Frankfurt, Germany.
Ganser
A
A
Seipelt
G
G
Ottmann
O G
OG
Mentzel
U
U
Geissler
G R
GR
Hoelzer
D
D
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
D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; D011994:Recombinant Proteins; D014810:Vitamin E; D016179:Granulocyte Colony-Stimulating Factor; D014212:Tretinoin