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, Hal Broxmeyer, G. Spitzer, A. LeMaistre, S. Hultman, G. Ventura, J. D. Tigaud, M. A. Cork, J. M. Trujilo, J. U. Gutterman, W. N. Hittelman

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

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 (>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.

Original languageEnglish (US)
Pages (from-to)1491-1498
Number of pages8
JournalBlood
Volume74
Issue number5
StatePublished - 1989
Externally publishedYes

Fingerprint

Myelodysplastic Syndromes
Hematopoiesis
Granulocyte-Macrophage Colony-Stimulating Factor
Clone Cells
Bone
Chromosomes
Cytogenetics
Bone Marrow Cells
Therapeutics
Preleukemia
Methylation
Lymphocytes
Macrophages
Granulocyte-Macrophage Progenitor Cells
Erythroid Precursor Cells
Pancytopenia
Polymorphism
Restoration
X Chromosome
DNA Methylation

ASJC Scopus subject areas

  • Hematology

Cite this

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. / Vadhan-Raj, S.; Broxmeyer, Hal; Spitzer, G.; LeMaistre, A.; Hultman, S.; Ventura, G.; Tigaud, J. D.; Cork, M. A.; Trujilo, J. M.; Gutterman, J. U.; Hittelman, W. N.

In: Blood, Vol. 74, No. 5, 1989, p. 1491-1498.

Research output: Contribution to journalArticle

Vadhan-Raj, S, Broxmeyer, H, Spitzer, G, LeMaistre, A, Hultman, S, Ventura, G, Tigaud, JD, Cork, MA, Trujilo, JM, Gutterman, JU & Hittelman, WN 1989, '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', Blood, vol. 74, no. 5, pp. 1491-1498.
Vadhan-Raj, S. ; Broxmeyer, Hal ; Spitzer, G. ; LeMaistre, A. ; Hultman, S. ; Ventura, G. ; Tigaud, J. D. ; Cork, M. A. ; Trujilo, J. M. ; Gutterman, J. U. ; Hittelman, W. N. / 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. In: Blood. 1989 ; Vol. 74, No. 5. pp. 1491-1498.
@article{f0acf73f21964d0eaf5a651289fa2274,
title = "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",
abstract = "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 (>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.",
author = "S. Vadhan-Raj and Hal Broxmeyer and G. Spitzer and A. LeMaistre and S. Hultman and G. Ventura and Tigaud, {J. D.} and Cork, {M. A.} and Trujilo, {J. M.} and Gutterman, {J. U.} and Hittelman, {W. N.}",
year = "1989",
language = "English (US)",
volume = "74",
pages = "1491--1498",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "5",

}

TY - JOUR

T1 - 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

AU - Vadhan-Raj, S.

AU - Broxmeyer, Hal

AU - Spitzer, G.

AU - LeMaistre, A.

AU - Hultman, S.

AU - Ventura, G.

AU - Tigaud, J. D.

AU - Cork, M. A.

AU - Trujilo, J. M.

AU - Gutterman, J. U.

AU - Hittelman, W. N.

PY - 1989

Y1 - 1989

N2 - 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 (>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.

AB - 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 (>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.

UR - http://www.scopus.com/inward/record.url?scp=0024470396&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024470396&partnerID=8YFLogxK

M3 - Article

C2 - 2676013

AN - SCOPUS:0024470396

VL - 74

SP - 1491

EP - 1498

JO - Blood

JF - Blood

SN - 0006-4971

IS - 5

ER -