Phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor following allogeneic bone marrow transplantation

John Nemunaitis, C. Dean Buckner, Frederick R. Appelbaum, Celestia S. Higano, Motomi (Tomi) Mori, James Bianco, Carol Epstein, John Lipani, John Hansen, Rainer Storb, E. Donnall Thomas, Jack W. Singer

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Forty-seven patients with hematologic neoplasia received recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) by daily 2-hour infusion following allogeneic bone marrow transplantation from HLA-identical sibling donors in a phase I-II dose-escalation trial. Dose levels ranged from 30 to 500 μg/m2/d. At doses at or below 250 μg/m2/d, toxicity felt to be caused by rhGM-CSF was negligible. However, three of five patients treated with 500 μg/m2/d had unacceptable side effects caused by rhGM-CSF. Two different graft-versus-host disease (GVHD) prophylactic regimens were administered. Twenty-seven evaluable patients were administered regimens that did not contain methotrexate (MTX) (Group I) and reached an absolute neutrophil count of 1,000/μL by a median of day 14. In contrast, 18 patients who received GVHD prophylactic regimens containing MTX (Group II) reached an absolute neutrophil count of 1,000/μL. on a median of day 20. Patients in Group I had fewer febrile days and, of those discharged, had shorter initial hospitalizations than patients in Group II. The overall incidence of severe acute GVHD (grade 2 or greater) in the rhGM-CSF-treated patients was 28% and was similar to that in historical "good risk" patients who did not receive rhGM-CSF. These preliminary data suggest rhGM-CSF is unlikely to exacerbate GVHD in HLA-identical sibling donor transplants and indicate the need for randomized trials of rhGM-CSF in allogeneic marrow transplant patients.

Original languageEnglish (US)
Pages (from-to)2065-2071
Number of pages7
JournalBlood
Volume77
Issue number9
StatePublished - May 1 1991
Externally publishedYes

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Homologous Transplantation
Granulocyte-Macrophage Colony-Stimulating Factor
Bone Marrow Transplantation
Bone
Grafts
Graft vs Host Disease
Transplants
Methotrexate
Siblings
Neutrophils
Tissue Donors
Toxicity
Hospitalization
Fever
Bone Marrow
Incidence

ASJC Scopus subject areas

  • Hematology

Cite this

Nemunaitis, J., Buckner, C. D., Appelbaum, F. R., Higano, C. S., Mori, M. T., Bianco, J., ... Singer, J. W. (1991). Phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor following allogeneic bone marrow transplantation. Blood, 77(9), 2065-2071.

Phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor following allogeneic bone marrow transplantation. / Nemunaitis, John; Buckner, C. Dean; Appelbaum, Frederick R.; Higano, Celestia S.; Mori, Motomi (Tomi); Bianco, James; Epstein, Carol; Lipani, John; Hansen, John; Storb, Rainer; Thomas, E. Donnall; Singer, Jack W.

In: Blood, Vol. 77, No. 9, 01.05.1991, p. 2065-2071.

Research output: Contribution to journalArticle

Nemunaitis, J, Buckner, CD, Appelbaum, FR, Higano, CS, Mori, MT, Bianco, J, Epstein, C, Lipani, J, Hansen, J, Storb, R, Thomas, ED & Singer, JW 1991, 'Phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor following allogeneic bone marrow transplantation', Blood, vol. 77, no. 9, pp. 2065-2071.
Nemunaitis, John ; Buckner, C. Dean ; Appelbaum, Frederick R. ; Higano, Celestia S. ; Mori, Motomi (Tomi) ; Bianco, James ; Epstein, Carol ; Lipani, John ; Hansen, John ; Storb, Rainer ; Thomas, E. Donnall ; Singer, Jack W. / Phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor following allogeneic bone marrow transplantation. In: Blood. 1991 ; Vol. 77, No. 9. pp. 2065-2071.
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abstract = "Forty-seven patients with hematologic neoplasia received recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) by daily 2-hour infusion following allogeneic bone marrow transplantation from HLA-identical sibling donors in a phase I-II dose-escalation trial. Dose levels ranged from 30 to 500 μg/m2/d. At doses at or below 250 μg/m2/d, toxicity felt to be caused by rhGM-CSF was negligible. However, three of five patients treated with 500 μg/m2/d had unacceptable side effects caused by rhGM-CSF. Two different graft-versus-host disease (GVHD) prophylactic regimens were administered. Twenty-seven evaluable patients were administered regimens that did not contain methotrexate (MTX) (Group I) and reached an absolute neutrophil count of 1,000/μL by a median of day 14. In contrast, 18 patients who received GVHD prophylactic regimens containing MTX (Group II) reached an absolute neutrophil count of 1,000/μL. on a median of day 20. Patients in Group I had fewer febrile days and, of those discharged, had shorter initial hospitalizations than patients in Group II. The overall incidence of severe acute GVHD (grade 2 or greater) in the rhGM-CSF-treated patients was 28{\%} and was similar to that in historical {"}good risk{"} patients who did not receive rhGM-CSF. These preliminary data suggest rhGM-CSF is unlikely to exacerbate GVHD in HLA-identical sibling donor transplants and indicate the need for randomized trials of rhGM-CSF in allogeneic marrow transplant patients.",
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AU - Higano, Celestia S.

AU - Mori, Motomi (Tomi)

AU - Bianco, James

AU - Epstein, Carol

AU - Lipani, John

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AU - Thomas, E. Donnall

AU - Singer, Jack W.

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