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
S Vadhan-Raj, HE Broxmeyer, G Spitzer, A LeMaistre, S Hultman, G Ventura, JD Tigaud, MA Cork, JM Trujillo and JU Gutterman
Department of Clinical Immunology, University of Texas M.D. Anderson Cancer
Center, Houston.
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.
Volume 74,
Issue 5,
pp. 1491-1498,
10/01/1989
Copyright © 1989 by The American Society of Hematology
