In vivo biologic effects of PIXY321, a synthetic hybrid protein of recombinant human granulocyte-macrophage colony-stimulating factor and interleukin-3 in cancer patients with normal hematopoiesis: A phase I study

Saroj Vadhan-Raj, Hal Broxmeyer, Michael Andreeff, Juan C. Bandres, E. Stephen Buescher, Robert S. Benjamin, Nicholas E. Papadopoulos, Andrew Burgess, Shreyaskumar Patel, Carl Plager, Walter N. Hittelman, Ian McAlister, Leslie Garrison, Douglas E. Williams

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

PIXY321 is a novel fusion protein of recombinant human granulocyte-macrophage colony-stimulating factor and interleukin-3 that exhibits biologic effects of both its parent cytokines in vitro and in preclinical studies. To evaluate the clinical safety and hematopoietic effects of this hybrid cytokine, PIXY321 was administered by subcutaneous injection twice daily at doses of 25 to 1,000 μg/m2/day over 14 days to 24 patients with sarcoma before chemotherapy as part of a phase I trial. The treatment was associated with significant increases in white blood cell, neutrophil, platelet, and reticulocyte counts (all P <.001). The increase in neutrophil count was dose-related and was seen during treatment with the cytokine, whereas the increase in platelet count was gradual and peaked after the cessation of the cytokine treatment and was not clearly dose related. PIXY321 treatment also increased bone marrow (BM) cellularity and the percentage of BM cells in S phase (P <.001). In addition, there was a significant increase in the number of CD34+ cells and committed and multipotential progenitors in the peripheral blood. The ex vivo expansion capacity of peripheral blood and BM progenitor cells was preserved after the in vivo treatment with PIXY321. The treatment was well tolerated, with the most common side-effect being injection site reactions. The results of this study show the biologic and clinical activity of a genetically engineered fusion molecule of two hematopoietic cytokines in humans with normal hematopoietic function.

Original languageEnglish (US)
Pages (from-to)2098-2105
Number of pages8
JournalBlood
Volume86
Issue number6
StatePublished - Sep 15 1995
Externally publishedYes

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Recombinant Fusion Proteins
Interleukin-3
Hematopoiesis
Granulocyte-Macrophage Colony-Stimulating Factor
Cytokines
Bone
Blood
Neoplasms
Platelets
Platelet Count
Bone Marrow Cells
Neutrophils
Reticulocyte Count
Therapeutics
Withholding Treatment
Chemotherapy
Subcutaneous Injections
S Phase
Leukocyte Count
Sarcoma

ASJC Scopus subject areas

  • Hematology

Cite this

In vivo biologic effects of PIXY321, a synthetic hybrid protein of recombinant human granulocyte-macrophage colony-stimulating factor and interleukin-3 in cancer patients with normal hematopoiesis : A phase I study. / Vadhan-Raj, Saroj; Broxmeyer, Hal; Andreeff, Michael; Bandres, Juan C.; Buescher, E. Stephen; Benjamin, Robert S.; Papadopoulos, Nicholas E.; Burgess, Andrew; Patel, Shreyaskumar; Plager, Carl; Hittelman, Walter N.; McAlister, Ian; Garrison, Leslie; Williams, Douglas E.

In: Blood, Vol. 86, No. 6, 15.09.1995, p. 2098-2105.

Research output: Contribution to journalArticle

Vadhan-Raj, S, Broxmeyer, H, Andreeff, M, Bandres, JC, Buescher, ES, Benjamin, RS, Papadopoulos, NE, Burgess, A, Patel, S, Plager, C, Hittelman, WN, McAlister, I, Garrison, L & Williams, DE 1995, 'In vivo biologic effects of PIXY321, a synthetic hybrid protein of recombinant human granulocyte-macrophage colony-stimulating factor and interleukin-3 in cancer patients with normal hematopoiesis: A phase I study', Blood, vol. 86, no. 6, pp. 2098-2105.
Vadhan-Raj, Saroj ; Broxmeyer, Hal ; Andreeff, Michael ; Bandres, Juan C. ; Buescher, E. Stephen ; Benjamin, Robert S. ; Papadopoulos, Nicholas E. ; Burgess, Andrew ; Patel, Shreyaskumar ; Plager, Carl ; Hittelman, Walter N. ; McAlister, Ian ; Garrison, Leslie ; Williams, Douglas E. / In vivo biologic effects of PIXY321, a synthetic hybrid protein of recombinant human granulocyte-macrophage colony-stimulating factor and interleukin-3 in cancer patients with normal hematopoiesis : A phase I study. In: Blood. 1995 ; Vol. 86, No. 6. pp. 2098-2105.
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abstract = "PIXY321 is a novel fusion protein of recombinant human granulocyte-macrophage colony-stimulating factor and interleukin-3 that exhibits biologic effects of both its parent cytokines in vitro and in preclinical studies. To evaluate the clinical safety and hematopoietic effects of this hybrid cytokine, PIXY321 was administered by subcutaneous injection twice daily at doses of 25 to 1,000 μg/m2/day over 14 days to 24 patients with sarcoma before chemotherapy as part of a phase I trial. The treatment was associated with significant increases in white blood cell, neutrophil, platelet, and reticulocyte counts (all P <.001). The increase in neutrophil count was dose-related and was seen during treatment with the cytokine, whereas the increase in platelet count was gradual and peaked after the cessation of the cytokine treatment and was not clearly dose related. PIXY321 treatment also increased bone marrow (BM) cellularity and the percentage of BM cells in S phase (P <.001). In addition, there was a significant increase in the number of CD34+ cells and committed and multipotential progenitors in the peripheral blood. The ex vivo expansion capacity of peripheral blood and BM progenitor cells was preserved after the in vivo treatment with PIXY321. The treatment was well tolerated, with the most common side-effect being injection site reactions. The results of this study show the biologic and clinical activity of a genetically engineered fusion molecule of two hematopoietic cytokines in humans with normal hematopoietic function.",
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AU - Broxmeyer, Hal

AU - Andreeff, Michael

AU - Bandres, Juan C.

AU - Buescher, E. Stephen

AU - Benjamin, Robert S.

AU - Papadopoulos, Nicholas E.

AU - Burgess, Andrew

AU - Patel, Shreyaskumar

AU - Plager, Carl

AU - Hittelman, Walter N.

AU - McAlister, Ian

AU - Garrison, Leslie

AU - Williams, Douglas E.

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