Stimulation of nonclonal hematopoiesis and suppression of the neoplastic clone after treatment with recombinant human granulocyte-macrophage colony-stimulating factor in a patient with therapy-related myelodysplastic syndrome.
A complete hematologic remission was achieved in a patient with therapy-related preleukemia and transfusion-dependent pancytopenia after treatment with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). The patient remained in remission for nearly 1 year despite the discontinuation of GM-CSF treatment. Several lines of evidence suggest that normal hematopoiesis was restored after GM-CSF treatment. First, the cytogenetic anomaly, which was present before GM-CSF, completely disappeared after three cycles of treatment. Cytogenetic conversion was documented by conventional karyotypic evaluation of mitotic bone marrow cell preparations as well as by premature chromosome condensation analysis of the nonmitotic cells of bone marrow and peripheral blood. Second, the growth pattern and cycle status of bone marrow granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) progenitor cells were found to be normal during remission. Third, X chromosome-linked restriction fragment length polymorphism-methylation analysis of DNA from mononuclear cells (greater than 80% lymphocytes) and mature myeloid elements showed a polyclonal pattern. These findings suggest that restoration of hematopoiesis in this patient after GM-CSF treatment may have resulted from suppression of the abnormal clone and a selective growth advantage of normal elements.
Vadhan-Raj
S
S
Department of Clinical Immunology, University of Texas M.D. Anderson Cancer Center, Houston.
Broxmeyer
H E
HE
Spitzer
G
G
LeMaistre
A
A
Hultman
S
S
Ventura
G
G
Tigaud
J D
JD
Cork
M A
MA
Trujillo
J M
JM
Gutterman
J U
JU
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000601:surgery; D015139:Blotting, Southern; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D003115:Colony-Stimulating Factors / Q000627:therapeutic use*; D004247:DNA / Q000235:genetics; D004906:Erythrocyte Count / Q000187:drug effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000627:therapeutic use*; D006400:Hematocrit; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007621:Karyotyping; D007958:Leukocyte Count / Q000187:drug effects; D008558:Melphalan / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D010976:Platelet Count / Q000187:drug effects; D011289:Preleukemia / Q000188:drug therapy* / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA; D008558:Melphalan