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.
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.
Aivado
M
M
Department of Hematology, Oncology and Clinical Immunolgy, Heinrich Heine University, Düsseldorf, Germany. aivado@uni-duesseldorf.de
Rong
A
A
Stadler
M
M
Germing
U
U
Giagounidis
A
A
Strupp
C
C
Novotny
J
J
Josten
K M
KM
Kobbe
G
G
Hildebrandt
B
B
Gattermann
N
N
Aul
C
C
Haas
R
R
Ganser
A
A
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
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents