Sequential administration of recombinant human interleukin-3 and granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for malignant lymphoma: A phase I/II multicenter study

Joseph W. Fay, Hillard Lazarus, Roger Herzig, Ruben Saez, Don A. Stevens, Robert H. Collins, Luis A. Piñeiro, Brenda W. Cooper, Joseph DiCesare, Marilyn Campion, James M. Felser, Geoffrey Herzig, Steven H. Bernstein

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Abstract

Preclinical studies of recombinant human interleukin-3 (rhlL-3) and granulocyte-macrophage colony-stimulating factor (rhGM-CSF) have shown enhancement of multilineage hematopoiesis when administered sequentially. This study was designed to evaluate the safety, tolerability, and biologic effects of sequential administration of rhlL-3 and rhGM-CSF after marrow ablative cytotoxic therapy and autologous bone marrow transplantation (ABMT) for patients with malignant lymphoma. Thirty-seven patients (20 patients with non-Hodgkin's lymphoma and 17 patients with Hodgkin's disease) received one of four different treatment regimens before ABMT. Patients were entered in one of four study groups to receive rhlL-3 (2.5 or 5.0 μg/kg/day) administered by subcutaneous injection for either 5 or 10 days starting 4 hours after the marrow infusion. Twenty-four hours after the last dose of rhlL-3, rhGM-CSF (250 μg/m2/d as a 2-hour intravenous infusion) administration was initiated. rhGM-CSF was administered daily until the absolute neutrophil count (ANC) was ≥1,500/μL for 3 consecutive days or until day 27 posttransplant. The most frequent adverse events in the trial included nausea, fever, diarrhea, mucositis, vomiting, rash, edema, chills, abdominal pain, and tachycardia. Three patients were removed from the study because of chest, skeletal, and abdominal pain felt to be probably related to study drug. Four patients died during the study period because of complications unrelated to either rhlL-3 or rhGM-CSF. The median time to recovery of neutrophils (ANC ≥500/μL and platelets (platelet count ≥20,000/μL) was 14 and 15 days, respectively. There were fewer days of platelet transfusions than seen in historical control groups using rhGM-CSF, rhG-CSF, or rhlL-3 alone. In addition, there were fewer days of red blood cell transfusions compared with historical controls using no cytokines or rhGM-CSF. These data indicate that the sequential administration of rhlL-3 and rhGM-CSF after ABMT is safe and generally well-tolerated and results in rapid recovery of multilineage hematopoiesis.

Original languageEnglish (US)
Pages (from-to)2151-2157
Number of pages7
JournalBlood
Volume84
Issue number7
StatePublished - Oct 1 1994

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Autologous Transplantation
Interleukin-3
Granulocyte-Macrophage Colony-Stimulating Factor
Bone Marrow Transplantation
Multicenter Studies
Lymphoma
Bone
Platelets
Neutrophils
Hematopoiesis
Abdominal Pain
Bone Marrow
Recovery
Erythrocyte Transfusion
Platelet Transfusion
Chills
Mucositis
Subcutaneous Injections
Exanthema
Chest Pain

ASJC Scopus subject areas

  • Hematology

Cite this

Sequential administration of recombinant human interleukin-3 and granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for malignant lymphoma : A phase I/II multicenter study. / Fay, Joseph W.; Lazarus, Hillard; Herzig, Roger; Saez, Ruben; Stevens, Don A.; Collins, Robert H.; Piñeiro, Luis A.; Cooper, Brenda W.; DiCesare, Joseph; Campion, Marilyn; Felser, James M.; Herzig, Geoffrey; Bernstein, Steven H.

In: Blood, Vol. 84, No. 7, 01.10.1994, p. 2151-2157.

Research output: Contribution to journalArticle

Fay, JW, Lazarus, H, Herzig, R, Saez, R, Stevens, DA, Collins, RH, Piñeiro, LA, Cooper, BW, DiCesare, J, Campion, M, Felser, JM, Herzig, G & Bernstein, SH 1994, 'Sequential administration of recombinant human interleukin-3 and granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for malignant lymphoma: A phase I/II multicenter study', Blood, vol. 84, no. 7, pp. 2151-2157.
Fay, Joseph W. ; Lazarus, Hillard ; Herzig, Roger ; Saez, Ruben ; Stevens, Don A. ; Collins, Robert H. ; Piñeiro, Luis A. ; Cooper, Brenda W. ; DiCesare, Joseph ; Campion, Marilyn ; Felser, James M. ; Herzig, Geoffrey ; Bernstein, Steven H. / Sequential administration of recombinant human interleukin-3 and granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for malignant lymphoma : A phase I/II multicenter study. In: Blood. 1994 ; Vol. 84, No. 7. pp. 2151-2157.
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abstract = "Preclinical studies of recombinant human interleukin-3 (rhlL-3) and granulocyte-macrophage colony-stimulating factor (rhGM-CSF) have shown enhancement of multilineage hematopoiesis when administered sequentially. This study was designed to evaluate the safety, tolerability, and biologic effects of sequential administration of rhlL-3 and rhGM-CSF after marrow ablative cytotoxic therapy and autologous bone marrow transplantation (ABMT) for patients with malignant lymphoma. Thirty-seven patients (20 patients with non-Hodgkin's lymphoma and 17 patients with Hodgkin's disease) received one of four different treatment regimens before ABMT. Patients were entered in one of four study groups to receive rhlL-3 (2.5 or 5.0 μg/kg/day) administered by subcutaneous injection for either 5 or 10 days starting 4 hours after the marrow infusion. Twenty-four hours after the last dose of rhlL-3, rhGM-CSF (250 μg/m2/d as a 2-hour intravenous infusion) administration was initiated. rhGM-CSF was administered daily until the absolute neutrophil count (ANC) was ≥1,500/μL for 3 consecutive days or until day 27 posttransplant. The most frequent adverse events in the trial included nausea, fever, diarrhea, mucositis, vomiting, rash, edema, chills, abdominal pain, and tachycardia. Three patients were removed from the study because of chest, skeletal, and abdominal pain felt to be probably related to study drug. Four patients died during the study period because of complications unrelated to either rhlL-3 or rhGM-CSF. The median time to recovery of neutrophils (ANC ≥500/μL and platelets (platelet count ≥20,000/μL) was 14 and 15 days, respectively. There were fewer days of platelet transfusions than seen in historical control groups using rhGM-CSF, rhG-CSF, or rhlL-3 alone. In addition, there were fewer days of red blood cell transfusions compared with historical controls using no cytokines or rhGM-CSF. These data indicate that the sequential administration of rhlL-3 and rhGM-CSF after ABMT is safe and generally well-tolerated and results in rapid recovery of multilineage hematopoiesis.",
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AU - Piñeiro, Luis A.

AU - Cooper, Brenda W.

AU - DiCesare, Joseph

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AU - Herzig, Geoffrey

AU - Bernstein, Steven H.

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N2 - Preclinical studies of recombinant human interleukin-3 (rhlL-3) and granulocyte-macrophage colony-stimulating factor (rhGM-CSF) have shown enhancement of multilineage hematopoiesis when administered sequentially. This study was designed to evaluate the safety, tolerability, and biologic effects of sequential administration of rhlL-3 and rhGM-CSF after marrow ablative cytotoxic therapy and autologous bone marrow transplantation (ABMT) for patients with malignant lymphoma. Thirty-seven patients (20 patients with non-Hodgkin's lymphoma and 17 patients with Hodgkin's disease) received one of four different treatment regimens before ABMT. Patients were entered in one of four study groups to receive rhlL-3 (2.5 or 5.0 μg/kg/day) administered by subcutaneous injection for either 5 or 10 days starting 4 hours after the marrow infusion. Twenty-four hours after the last dose of rhlL-3, rhGM-CSF (250 μg/m2/d as a 2-hour intravenous infusion) administration was initiated. rhGM-CSF was administered daily until the absolute neutrophil count (ANC) was ≥1,500/μL for 3 consecutive days or until day 27 posttransplant. The most frequent adverse events in the trial included nausea, fever, diarrhea, mucositis, vomiting, rash, edema, chills, abdominal pain, and tachycardia. Three patients were removed from the study because of chest, skeletal, and abdominal pain felt to be probably related to study drug. Four patients died during the study period because of complications unrelated to either rhlL-3 or rhGM-CSF. The median time to recovery of neutrophils (ANC ≥500/μL and platelets (platelet count ≥20,000/μL) was 14 and 15 days, respectively. There were fewer days of platelet transfusions than seen in historical control groups using rhGM-CSF, rhG-CSF, or rhlL-3 alone. In addition, there were fewer days of red blood cell transfusions compared with historical controls using no cytokines or rhGM-CSF. These data indicate that the sequential administration of rhlL-3 and rhGM-CSF after ABMT is safe and generally well-tolerated and results in rapid recovery of multilineage hematopoiesis.

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