title: Erythropoietin treatment in advanced multiple myeloma is associated with improved immunological functions: could it be beneficial in early disease?
abstract: Erythropoietin (Epo) is the main growth regulator of red blood cells, and recombinant human erythropoietin (rHuEpo) is thus used in clinical practice for the treatment of anaemia, primarily in kidney disease and cancer. rHuEpo treatment was found to be associated with prolonged survival of multiple myeloma (MM) patients. This clinical observation was then supported by studies on murine myeloma models. It thus appeared that rHuEpo had an anti-myeloma effect, causally related to an immunomodulatory function of rHuEpo. The present study investigated whether rHuEpo-treated MM patients acquire improved immunological functions. Treatment with rHuEpo, prescribed for anaemia that occurs in advanced disease, was associated with effects on a variety of immunological parameters and functions. This was expressed in an actual normalisation of the CD4:CD8 cell ratio, enhanced T cell phytohaemagglutinin-mediated activation and proliferation potential, T cell expression of the costimulatory CD28 and inhibitory CTLA-4 molecules, as well as reduced interleukin-6 serum values to normal levels. Furthermore, it was demonstrated that immunological abnormalities manifest in patients even in the early stages of MM. Our findings thus suggest that rHuEpo treatment might be effective in the early stages of MM, before anaemia develops. It is expected that this would boost the immune system, consequently achieving an anti-myeloma function; affecting disease progression and improving the prognosis.
authors.affiliation: Cell and Developmental Biology, Rabin Medical Centre, Golda-Hasharon Campus, Petah-Tikya, Israel.
authors.forename: Sara
authors.initials: S
authors.lastname: Prutchi-Sagiv
authors.forename: Natalia
authors.initials: N
authors.lastname: Golishevsky
authors.forename: Howard S
authors.initials: HS
authors.lastname: Oster
authors.forename: Odelia
authors.initials: O
authors.lastname: Katz
authors.forename: Amos
authors.initials: A
authors.lastname: Cohen
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Naparstek
authors.forename: Drorit
authors.initials: D
authors.lastname: Neumann
authors.forename: Moshe
authors.initials: M
authors.lastname: Mittelman
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D018106:CD28 Antigens / Q000032:analysis; D016516:CD4-CD8 Ratio; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D018450:Disease Progression; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000097:blood; D037181:Lectins, C-Type; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; D004921:Erythropoietin; D006454:Hemoglobins; D015850:Interleukin-6; D037181:Lectins, C-Type; D011994:Recombinant Proteins; D000099192:CD69 Antigens; C556706:CTLA4 protein, human