Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes

S. Vadhan-Raj, M. Keating, A. LeMaistre, W. N. Hittelman, K. McCredie, J. M. Trujillo, Hal Broxmeyer, Ch Henney, J. U. Gutterman

Research output: Contribution to journalArticle

432 Citations (Scopus)

Abstract

The myelodysplastic syndromes are characterized by ineffective hematopoiesis and refractory cytopenias. In an attempt to improve hematopoiesis, we administered recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) to eight patients with myelodysplastic syndrome, as part of a Phase I trial. The GM-CSF was given by continuous intravenous infusion daily for two weeks and then again after a two-week rest period. Over the entire dose range tested (30 to 500 μg per square meter of body-surface area), treatment was associated with marked increases in peripheral-blood leukocytes (5- to 70-fold), including granulocytes (5- to 373-fold), in all eight patients. The absolute number of monocytes, eosinophils, and lymphocytes increased in all patients. Three of eight patients also had 2- to 10-fold increases in platelet counts and improvement in erythropoiesis, with the result that two of three patients who had required red-cell and platelet transfusions no longer needed them (at 20 to 27 weeks of follow-up). Treatment was also associated with increased marrow cellularity and a decreased percentage of blasts in the bone marrow of patients with excess blasts, resulting in an increase in the ratio of differentiated myeloid cells to immature myeloid cells. We observed relatively few side effects, but bone pain was dose-limiting when it was associated with high white-cell counts. Our results showed that GM-CSF is a potent stimulator of hematopoiesis in vivo and may produce hematologic improvement in the short term (8 to 32 weeks of observation) in patients with myelodysplastic syndrome. More experience, with longer follow-up periods, will be necessary to assess the long-term safety and efficacy of this new treatment.

Original languageEnglish (US)
Pages (from-to)1545-1552
Number of pages8
JournalNew England Journal of Medicine
Volume317
Issue number25
StatePublished - 1987

Fingerprint

Myelodysplastic Syndromes
Granulocyte-Macrophage Colony-Stimulating Factor
Hematopoiesis
Myeloid Cells
Bone Marrow
Platelet Transfusion
Erythropoiesis
Body Surface Area
Platelet Count
Granulocytes
Eosinophils
Intravenous Infusions
Monocytes
Leukocytes
Cell Count
Observation
Lymphocytes
Safety
Bone and Bones
Pain

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Vadhan-Raj, S., Keating, M., LeMaistre, A., Hittelman, W. N., McCredie, K., Trujillo, J. M., ... Gutterman, J. U. (1987). Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes. New England Journal of Medicine, 317(25), 1545-1552.

Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes. / Vadhan-Raj, S.; Keating, M.; LeMaistre, A.; Hittelman, W. N.; McCredie, K.; Trujillo, J. M.; Broxmeyer, Hal; Henney, Ch; Gutterman, J. U.

In: New England Journal of Medicine, Vol. 317, No. 25, 1987, p. 1545-1552.

Research output: Contribution to journalArticle

Vadhan-Raj, S, Keating, M, LeMaistre, A, Hittelman, WN, McCredie, K, Trujillo, JM, Broxmeyer, H, Henney, C & Gutterman, JU 1987, 'Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes', New England Journal of Medicine, vol. 317, no. 25, pp. 1545-1552.
Vadhan-Raj S, Keating M, LeMaistre A, Hittelman WN, McCredie K, Trujillo JM et al. Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes. New England Journal of Medicine. 1987;317(25):1545-1552.
Vadhan-Raj, S. ; Keating, M. ; LeMaistre, A. ; Hittelman, W. N. ; McCredie, K. ; Trujillo, J. M. ; Broxmeyer, Hal ; Henney, Ch ; Gutterman, J. U. / Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes. In: New England Journal of Medicine. 1987 ; Vol. 317, No. 25. pp. 1545-1552.
@article{c135255198ad4f05865e347a899d37ab,
title = "Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes",
abstract = "The myelodysplastic syndromes are characterized by ineffective hematopoiesis and refractory cytopenias. In an attempt to improve hematopoiesis, we administered recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) to eight patients with myelodysplastic syndrome, as part of a Phase I trial. The GM-CSF was given by continuous intravenous infusion daily for two weeks and then again after a two-week rest period. Over the entire dose range tested (30 to 500 μg per square meter of body-surface area), treatment was associated with marked increases in peripheral-blood leukocytes (5- to 70-fold), including granulocytes (5- to 373-fold), in all eight patients. The absolute number of monocytes, eosinophils, and lymphocytes increased in all patients. Three of eight patients also had 2- to 10-fold increases in platelet counts and improvement in erythropoiesis, with the result that two of three patients who had required red-cell and platelet transfusions no longer needed them (at 20 to 27 weeks of follow-up). Treatment was also associated with increased marrow cellularity and a decreased percentage of blasts in the bone marrow of patients with excess blasts, resulting in an increase in the ratio of differentiated myeloid cells to immature myeloid cells. We observed relatively few side effects, but bone pain was dose-limiting when it was associated with high white-cell counts. Our results showed that GM-CSF is a potent stimulator of hematopoiesis in vivo and may produce hematologic improvement in the short term (8 to 32 weeks of observation) in patients with myelodysplastic syndrome. More experience, with longer follow-up periods, will be necessary to assess the long-term safety and efficacy of this new treatment.",
author = "S. Vadhan-Raj and M. Keating and A. LeMaistre and Hittelman, {W. N.} and K. McCredie and Trujillo, {J. M.} and Hal Broxmeyer and Ch Henney and Gutterman, {J. U.}",
year = "1987",
language = "English (US)",
volume = "317",
pages = "1545--1552",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "25",

}

TY - JOUR

T1 - Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes

AU - Vadhan-Raj, S.

AU - Keating, M.

AU - LeMaistre, A.

AU - Hittelman, W. N.

AU - McCredie, K.

AU - Trujillo, J. M.

AU - Broxmeyer, Hal

AU - Henney, Ch

AU - Gutterman, J. U.

PY - 1987

Y1 - 1987

N2 - The myelodysplastic syndromes are characterized by ineffective hematopoiesis and refractory cytopenias. In an attempt to improve hematopoiesis, we administered recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) to eight patients with myelodysplastic syndrome, as part of a Phase I trial. The GM-CSF was given by continuous intravenous infusion daily for two weeks and then again after a two-week rest period. Over the entire dose range tested (30 to 500 μg per square meter of body-surface area), treatment was associated with marked increases in peripheral-blood leukocytes (5- to 70-fold), including granulocytes (5- to 373-fold), in all eight patients. The absolute number of monocytes, eosinophils, and lymphocytes increased in all patients. Three of eight patients also had 2- to 10-fold increases in platelet counts and improvement in erythropoiesis, with the result that two of three patients who had required red-cell and platelet transfusions no longer needed them (at 20 to 27 weeks of follow-up). Treatment was also associated with increased marrow cellularity and a decreased percentage of blasts in the bone marrow of patients with excess blasts, resulting in an increase in the ratio of differentiated myeloid cells to immature myeloid cells. We observed relatively few side effects, but bone pain was dose-limiting when it was associated with high white-cell counts. Our results showed that GM-CSF is a potent stimulator of hematopoiesis in vivo and may produce hematologic improvement in the short term (8 to 32 weeks of observation) in patients with myelodysplastic syndrome. More experience, with longer follow-up periods, will be necessary to assess the long-term safety and efficacy of this new treatment.

AB - The myelodysplastic syndromes are characterized by ineffective hematopoiesis and refractory cytopenias. In an attempt to improve hematopoiesis, we administered recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) to eight patients with myelodysplastic syndrome, as part of a Phase I trial. The GM-CSF was given by continuous intravenous infusion daily for two weeks and then again after a two-week rest period. Over the entire dose range tested (30 to 500 μg per square meter of body-surface area), treatment was associated with marked increases in peripheral-blood leukocytes (5- to 70-fold), including granulocytes (5- to 373-fold), in all eight patients. The absolute number of monocytes, eosinophils, and lymphocytes increased in all patients. Three of eight patients also had 2- to 10-fold increases in platelet counts and improvement in erythropoiesis, with the result that two of three patients who had required red-cell and platelet transfusions no longer needed them (at 20 to 27 weeks of follow-up). Treatment was also associated with increased marrow cellularity and a decreased percentage of blasts in the bone marrow of patients with excess blasts, resulting in an increase in the ratio of differentiated myeloid cells to immature myeloid cells. We observed relatively few side effects, but bone pain was dose-limiting when it was associated with high white-cell counts. Our results showed that GM-CSF is a potent stimulator of hematopoiesis in vivo and may produce hematologic improvement in the short term (8 to 32 weeks of observation) in patients with myelodysplastic syndrome. More experience, with longer follow-up periods, will be necessary to assess the long-term safety and efficacy of this new treatment.

UR - http://www.scopus.com/inward/record.url?scp=0023571993&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023571993&partnerID=8YFLogxK

M3 - Article

C2 - 3500414

AN - SCOPUS:0023571993

VL - 317

SP - 1545

EP - 1552

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 25

ER -