Document Detail

Prolonged response to cyclosporin-A in hypoplastic refractory anemia and correlation with in vitro studies.
MedLine Citation:
PMID:  10681719     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND OBJECTIVE: Lymphocyte abnormalities in myelodysplastic syndromes (MDS) have been widely described, but the role of the immune system in the pathogenesis of these clonal disorders remains controversial. An active role of lymphocytes in suppressing normal hematopoiesis may be implicated in MDS with hypoplastic marrow. We have studied in vitro and in vivo activity of cyclosporin-A (CSA) on hematopoiesis in patients affected by hypoplastic MDS without blast excess. DESIGN AND METHODS: Nine consecutive patients with hypoplastic refractory anemia (RA), followed up in our out-patient unit, were treated with CSA at daily doses of 1-3 mg/kg for at least three months. Low dose steroids or danazol were transiently added in 7/9 patients. Differences between pre- and post-treatment parameters were studied by the Student's t-test. In vitro effect of CSA on circulating hematopoietic progenitors was studied by the methylcellulose colony assay. RESULTS: Before treatment, fewer circulating hematopoietic progenitors were found in all patients as compared to normal subjects. The number of CD34+ cells was about halved, while circulating erythroid and myeloid colony-forming cells (CFC) were reduced to one-fifth. After a mean period of 22 months of CSA treatment (median: 14.5 months), hemoglobin was significantly and persistently increased in two patients, platelets in one, platelets and hemoglobin in two. Two patients showed transient responses, one patient did not tolerate the treatment and one patient is close to a significant response. At in vitro CSA concentrations similar to those achieved in vivo after oral administration the drug significantly increased cell colony growth in hypoplastic RA. This test correctly predicted a positive clinical response to CSA in 3/5 cases and treatment failure in 4/4 cases. INTERPRETATION AND CONCLUSIONS: About one half of hypoplastic RA patients benefited from CSA treatment. A larger study could verify whether in vitro culture of hematopoietic progenitors in the presence of CSA can predict the clinical response and whether this treatment could prolong patients' survival.
L Catalano; C Selleri; C Califano; L Luciano; M Volpicelli; S Rocco; G Varriale; P Ricci; B Rotoli
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Haematologica     Volume:  85     ISSN:  0390-6078     ISO Abbreviation:  Haematologica     Publication Date:  2000 Feb 
Date Detail:
Created Date:  2000-05-23     Completed Date:  2000-05-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0417435     Medline TA:  Haematologica     Country:  ITALY    
Other Details:
Languages:  eng     Pagination:  133-8     Citation Subset:  IM    
Division of Hematology, Federico II University, via S. Pansini 5, 80131 Naples, Italy.
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MeSH Terms
Anemia, Refractory / drug therapy*,  pathology,  physiopathology
Cells, Cultured
Colony-Forming Units Assay
Cyclosporine / administration & dosage*
Hematopoiesis / drug effects
Hematopoietic Stem Cells / drug effects
Immunosuppressive Agents / administration & dosage*
Middle Aged
Treatment Outcome
Reg. No./Substance:
0/Immunosuppressive Agents; 59865-13-3/Cyclosporine

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