title: Favourable response to antithymocyte or antilymphocyte globulin in low-risk myelodysplastic syndrome patients with a 'non-clonal' pattern of X-chromosome inactivation in bone marrow cells.
abstract: OBJECTIVE
  Antithymocyte and antilymphocyte globulin (ATG/ALG) have a therapeutic effect in about 30% of patients with myelodysplastic syndromes (MDS). We were interested to know whether responding patients achieve clonal or polyclonal remissions.
  
  
  METHODS
  Ten women with low-risk MDS received either ALG or ATG. Before treatment and 3, 6, and 12 months later, X-chromosome inactivation patterns of peripheral blood T lymphocytes were compared with those of peripheral blood granulocytes or bone marrow cells, using the human androgen receptor gene assay and the phosphoglycerate kinase-1 assay.
  
  
  RESULTS
  Six women did not respond to therapy. Prior to treatment, four of them had a monoclonal, one had an oligoclonal, and one had a skewed X-chromosome inactivation pattern (XCIP). Four patients responded to ATG/ALG. Three of them were informative in our X-inactivation assays, and showed a non-clonal XCIP which did not change significantly after treatment with ATG/ALG.
  
  
  CONCLUSIONS
  A non-clonal XCIP in the bone marrow was associated with a response to ATG/ALG. Non-clonal XCIPs do not necessarily imply that there is no pathological clone. By definition, they just indicate that there is no evidence of a clone contributing more than 50% of cells in a sample. Non-clonal XCIPs may therefore be attributable to incomplete clonal expansion. This, in turn, might be explained by a vigorous immune attack against the MDS clone, which simultaneously causes collateral damage in the remaining normal haemopoiesis. In such patients, ATG/ALG may improve normal haemopoiesis by relieving the immunological pressure on the innocent bystanders.
authors.affiliation: Department of Hematology, Oncology and Clinical Immunolgy, Heinrich Heine University, Düsseldorf, Germany. aivado@uni-duesseldorf.de
authors.forename: M
authors.initials: M
authors.lastname: Aivado
authors.forename: A
authors.initials: A
authors.lastname: Rong
authors.forename: M
authors.initials: M
authors.lastname: Stadler
authors.forename: U
authors.initials: U
authors.lastname: Germing
authors.forename: A
authors.initials: A
authors.lastname: Giagounidis
authors.forename: C
authors.initials: C
authors.lastname: Strupp
authors.forename: J
authors.initials: J
authors.lastname: Novotny
authors.forename: K M
authors.initials: KM
authors.lastname: Josten
authors.forename: G
authors.initials: G
authors.lastname: Kobbe
authors.forename: B
authors.initials: B
authors.lastname: Hildebrandt
authors.forename: N
authors.initials: N
authors.lastname: Gattermann
authors.forename: C
authors.initials: C
authors.lastname: Aul
authors.forename: R
authors.initials: R
authors.lastname: Haas
authors.forename: A
authors.initials: A
authors.lastname: Ganser
mesh_terms: D000368:Aged; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D001854:Bone Marrow Cells / Q000473:pathology*; D002454:Cell Differentiation; D004303:Dosage Compensation, Genetic; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007275:Injections, Intravenous; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents