TY - JOUR
TI - Effect of cA2 anti-tumor necrosis factor-α antibody therapy on hematopoiesis of patients with myelodysplastic syndromes
AU - Boula, A.
AU - Voulgarelis, M.
AU - Giannouli, S.
AU - Katrinakis, G.
AU - Psyllaki, M.
AU - Pontikoglou, C.
AU - Markidou, F.
AU - Eliopoulos, G.D.
AU - Papadaki, H.A.
JO - Clinical Cancer Research
PY - 2006
VL - 12
TODO - 10
SP - 3099-3108
PB - 
SN - 1078-0432
TODO - 10.1158/1078-0432.CCR-06-0254
TODO - 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
TODO - 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.
ER -