Τίτλος:
Effect of cA2 anti-tumor necrosis factor-α antibody therapy on hematopoiesis of patients with myelodysplastic syndromes
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Purpose: Tumor necrosis factor α (TNF-α) plays a prominent role in the pathophysiology of myelodysplastic syndromes (MDS). The aim of this study was to explore the biological and immunoregulatory effect of the treatment with the anti-tumor necrosis factor-α monoclonal antibody cA2 on bone marrow (BM) progenitor/precursor and stromal cells and lymphocyte subsets, as well as the clinical response in MDS patients. Experimental Design: Ten low-intermediate risk MDS patients received i.v. cA2 (3 mg/kg) at weeks 0, 2, 6, and 12. The number, survival, and clonogenic potential of BM progenitor/precursor cells, the hematopoiesis-supporting capacity of BM stromal cells, and the lymphocyte activation status were investigated in the patients at baseline and following treatment using flow cytometry, clonogenic assays, and long-term BM cultures (LTBMC). Clinical response was evaluated according to standardized criteria. Results: cA2 administration reduced the proportion of apoptotic and Fas+ cells in the CD34+ cell compartment (P = 0.0215 and P = 0.0344, respectively) and increased the clonogenic potential of BM mononuclear and CD34+ cells (P = 0.0399 and P = 0.0304, respectively) compared with baseline. The antibody reduced tumor necrosis factor-α levels in LTBMC supernatants (P = 0.0043) and significantly improved the hematopoiesis-supporting capacity of LTBMC adherent cells. The proportion of activated peripheral blood and BM T-lymphocytes decreased significantly after treatment, suggesting an immunomodulatory effect of cA2. Two patients displayed minor hematologic responses whereas the remaining patients displayed stable disease with no disease progression. Conclusions: The encouraging biological insights from cA2 administration may be useful in conducting further clinical trials using cA2 for selected MDS patients, particularly those with evidence of immune-mediated inhibition of hematopoiesis. © 2006 American Association for Cancer Research.
Συγγραφείς:
Boula, A.
Voulgarelis, M.
Giannouli, S.
Katrinakis, G.
Psyllaki, M.
Pontikoglou, C.
Markidou, F.
Eliopoulos, G.D.
Papadaki, H.A.
Περιοδικό:
Clinical Cancer Research
Λέξεις-κλειδιά:
CD34 antigen; Fas antigen; monoclonal antibody; monoclonal antibody tumor necrosis factor alpha ca 2; tumor necrosis factor alpha; unclassified drug, adult; aged; apoptosis; article; bone marrow; cell culture; clinical article; clonogenic assay; controlled study; drug effect; female; hematopoiesis; human; human cell; immunomodulation; immunoregulation; lymphocyte activation; male; mononuclear cell; myelodysplastic syndrome; priority journal; stem cell; stroma cell; survival; treatment response, Aged; Antibodies, Monoclonal; Apoptosis; Female; Flow Cytometry; Gastrointestinal Agents; Hematopoiesis; Humans; Lymphocyte Activation; Lymphocyte Subsets; Male; Middle Aged; Myelodysplastic Syndromes; Tumor Necrosis Factor-alpha
DOI:
10.1158/1078-0432.CCR-06-0254
