Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor in Aplastic Anemia: A Phase I/II Trial with Emphasis on Very Severe Neutropenia and Active Infection

1992 ◽  
pp. 555-563 ◽  
Author(s):  
A. Raghavachar ◽  
W. Hinterberger ◽  
J. P. Kaltwasser ◽  
K. Höffken ◽  
F. Herrmann ◽  
...  
Keyword(s):  
Phase I ◽  
Aplastic Anemia ◽  
Severe Neutropenia ◽  
Colony Stimulating Factor ◽  
Active Infection ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

scholarly journals A phase I/II trial of recombinant granulocyte-macrophage colony- stimulating factor for children with aplastic anemia

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1077-1082 ◽  
Author(s):  
EC Guinan ◽  
CA Sieff ◽  
DH Oette ◽  
DG Nathan
Keyword(s):  
Phase I ◽  
Aplastic Anemia ◽  
Significant Rise ◽  
Drug Discontinuation ◽  
Newly Diagnosed ◽  
Colony Stimulating Factor ◽  
Fourfold Increase ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Nine pediatric patients (median age, 8 years; range, 0.7 to 19 years), eight with refractory aplastic anemia and one with newly diagnosed aplasia, were enrolled in a phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) administered via continuous intravenous infusion. Doses ranged from 8 to 32 micrograms/kg/d. Six of eight evaluable patients responded with a significant rise in neutrophil count (median fourfold increase; range, 2.5- to 31-fold) during the 28-day induction period. Five patients completed 2 further months of therapy (maintenance) with persistent or improved neutrophil responses. Three patients had bone marrow aspirates suggestive of increased erythropoiesis, although only one patient had improvement in peripheral hematocrit and platelet count. In the five patients completing maintenance, three experienced a rapid return to baseline counts after rhGM-CSF was discontinued, one maintained a neutrophil response for 2 months after drug discontinuation, and one has maintained a trilineage response for greater than 1 year off study. Drug therapy was well tolerated. Toxicity was minimal at doses from 8 to 16 micrograms/kg/d. Fever and rash were more commonly seen at 32 micrograms/kg/d. No patient developed an infection during the course of rhGM-CSF administration. These results demonstrate that rhGM-CSF increases peripheral neutrophil counts in children with refractory and newly diagnosed aplastic anemia and may be able to stimulate a multilineage response in a more limited number. Randomized, prospective trials are necessary to determine if rhGM-CSF administration will impact favorably on the morbidity and mortality of severe aplastic anemia.

scholarly journals Phase I/II study of recombinant human granulocyte-macrophage colony- stimulating factor in aplastic anemia and myelodysplastic syndrome

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 705-713 ◽  
Author(s):  
JH Antin ◽  
BR Smith ◽  
W Holmes ◽  
DS Rosenthal
Keyword(s):  
Myelodysplastic Syndrome ◽  
Phase I ◽  
Aplastic Anemia ◽  
Myelodysplastic Syndromes ◽  
Low Grade ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract We performed a phase I/II study of the administration of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) to patients with aplastic anemia or myelodysplastic syndrome. Doses ranging from 15 to 480 micrograms/m2 were administered as a one-hour or four-hour intravenous infusion daily for 7 days or as a 12-hour infusion for 14 days. Temporary improvements were seen in granulocyte counts, monocyte counts, and reticulocyte counts in six of eight patients with aplastic anemia and five of seven patients with myelodysplastic syndromes. The patients with myelodysplastic syndromes had larger increases in granulocyte, monocyte, and reticulocyte counts than did those with aplastic anemia, and they also had increases in the numbers of eosinophils (two of seven), immature myeloid cells (two of seven), and myeloblasts (two of seven) that were not observed in patients with aplastic anemia. There was no reduction in erythrocyte transfusion requirements, and no effect was observed on platelet counts. There was only minimal toxicity consisting of transient low- back discomfort, anorexia, myalgias/arthralgias, and low-grade fever. Our data suggest that GM-CSF is well tolerated and is more likely to result in elevations of blood counts in patients with myelodysplasia than in patients with aplastic anemia, but the role of GM-CSF therapy in these disorders remains to be determined.

scholarly journals Failure of recombinant human granulocyte-macrophage colony-stimulating factor therapy in aplastic anemia patients with very severe neutropenia

Blood ◽  
1988 ◽  
Vol 72 (6) ◽  
pp. 2045-2047
Author(s):  
C Nissen ◽  
A Tichelli ◽  
A Gratwohl ◽  
B Speck ◽  
A Milne ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Vena Cava ◽  
Severe Infection ◽  
Severe Neutropenia ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Minimal Residual

Four patients with very severe aplastic anemia refractory to antilymphocyte globulin were administered recombinant human granulocyte- macrophage--colony stimulating factor (GM-CSF). One patient with minimal residual myelopoiesis responded transiently to two separate courses of GM-CSF at 4 and 8 micrograms/kg/d administered intravenously and another course at 4 micrograms/kg/d administered subcutaneously. Septicemia and bilateral pneumonia that had been resistant to conventional therapy resolved. Three patients with no evidence of residual myelopoiesis did not respond to GM-CSF. In one patient, the dose was increased to 32 micrograms/kg/d with no effect on hematopoiesis. Immediate side effects were minimal at GM-CSF doses up to 16 micrograms/kg/d. GM-CSF may, however, have been involved in the pathophysiology of thrombosis of the inferior vena cava in the patient administered 32 micrograms/kg/d. We conclude that GM-CSF does not induce hematopoiesis in long-standing, severe, treatment-resistant aplastic anemia with complete myelopoietic failure. However, in patients with minimal residual myelopoiesis, GM-CSF could be a promising adjuvant therapy for severe infection.

scholarly journals A phase I/II trial of recombinant granulocyte-macrophage colony- stimulating factor for children with aplastic anemia

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1077-1082
Author(s):  
EC Guinan ◽  
CA Sieff ◽  
DH Oette ◽  
DG Nathan
Keyword(s):  
Phase I ◽  
Aplastic Anemia ◽  
Significant Rise ◽  
Drug Discontinuation ◽  
Newly Diagnosed ◽  
Colony Stimulating Factor ◽  
Fourfold Increase ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Nine pediatric patients (median age, 8 years; range, 0.7 to 19 years), eight with refractory aplastic anemia and one with newly diagnosed aplasia, were enrolled in a phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) administered via continuous intravenous infusion. Doses ranged from 8 to 32 micrograms/kg/d. Six of eight evaluable patients responded with a significant rise in neutrophil count (median fourfold increase; range, 2.5- to 31-fold) during the 28-day induction period. Five patients completed 2 further months of therapy (maintenance) with persistent or improved neutrophil responses. Three patients had bone marrow aspirates suggestive of increased erythropoiesis, although only one patient had improvement in peripheral hematocrit and platelet count. In the five patients completing maintenance, three experienced a rapid return to baseline counts after rhGM-CSF was discontinued, one maintained a neutrophil response for 2 months after drug discontinuation, and one has maintained a trilineage response for greater than 1 year off study. Drug therapy was well tolerated. Toxicity was minimal at doses from 8 to 16 micrograms/kg/d. Fever and rash were more commonly seen at 32 micrograms/kg/d. No patient developed an infection during the course of rhGM-CSF administration. These results demonstrate that rhGM-CSF increases peripheral neutrophil counts in children with refractory and newly diagnosed aplastic anemia and may be able to stimulate a multilineage response in a more limited number. Randomized, prospective trials are necessary to determine if rhGM-CSF administration will impact favorably on the morbidity and mortality of severe aplastic anemia.

scholarly journals Failure of recombinant human granulocyte-macrophage colony-stimulating factor therapy in aplastic anemia patients with very severe neutropenia

Blood ◽  
1988 ◽  
Vol 72 (6) ◽  
pp. 2045-2047 ◽  
Author(s):  
C Nissen ◽  
A Tichelli ◽  
A Gratwohl ◽  
B Speck ◽  
A Milne ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Vena Cava ◽  
Severe Infection ◽  
Severe Neutropenia ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Minimal Residual

Abstract Four patients with very severe aplastic anemia refractory to antilymphocyte globulin were administered recombinant human granulocyte- macrophage--colony stimulating factor (GM-CSF). One patient with minimal residual myelopoiesis responded transiently to two separate courses of GM-CSF at 4 and 8 micrograms/kg/d administered intravenously and another course at 4 micrograms/kg/d administered subcutaneously. Septicemia and bilateral pneumonia that had been resistant to conventional therapy resolved. Three patients with no evidence of residual myelopoiesis did not respond to GM-CSF. In one patient, the dose was increased to 32 micrograms/kg/d with no effect on hematopoiesis. Immediate side effects were minimal at GM-CSF doses up to 16 micrograms/kg/d. GM-CSF may, however, have been involved in the pathophysiology of thrombosis of the inferior vena cava in the patient administered 32 micrograms/kg/d. We conclude that GM-CSF does not induce hematopoiesis in long-standing, severe, treatment-resistant aplastic anemia with complete myelopoietic failure. However, in patients with minimal residual myelopoiesis, GM-CSF could be a promising adjuvant therapy for severe infection.

scholarly journals Phase I/II study of recombinant human granulocyte-macrophage colony- stimulating factor in aplastic anemia and myelodysplastic syndrome

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 705-713
Author(s):  
JH Antin ◽  
BR Smith ◽  
W Holmes ◽  
DS Rosenthal
Keyword(s):  
Myelodysplastic Syndrome ◽  
Phase I ◽  
Aplastic Anemia ◽  
Myelodysplastic Syndromes ◽  
Low Grade ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

We performed a phase I/II study of the administration of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) to patients with aplastic anemia or myelodysplastic syndrome. Doses ranging from 15 to 480 micrograms/m2 were administered as a one-hour or four-hour intravenous infusion daily for 7 days or as a 12-hour infusion for 14 days. Temporary improvements were seen in granulocyte counts, monocyte counts, and reticulocyte counts in six of eight patients with aplastic anemia and five of seven patients with myelodysplastic syndromes. The patients with myelodysplastic syndromes had larger increases in granulocyte, monocyte, and reticulocyte counts than did those with aplastic anemia, and they also had increases in the numbers of eosinophils (two of seven), immature myeloid cells (two of seven), and myeloblasts (two of seven) that were not observed in patients with aplastic anemia. There was no reduction in erythrocyte transfusion requirements, and no effect was observed on platelet counts. There was only minimal toxicity consisting of transient low- back discomfort, anorexia, myalgias/arthralgias, and low-grade fever. Our data suggest that GM-CSF is well tolerated and is more likely to result in elevations of blood counts in patients with myelodysplasia than in patients with aplastic anemia, but the role of GM-CSF therapy in these disorders remains to be determined.

Phase I Trial of Infusional Cyclophosphamide, Doxorubicin, and Etoposide plus Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in Non-Hodgkin's Lymphoma

2005 ◽  
Vol 22 (3) ◽  
pp. 257-268 ◽  
Author(s):  
Joseph A. Sparano ◽  
Abdissa Negassa ◽  
Erick Lansigan ◽  
Robin Locke ◽  
Chamath R. De Silva ◽  
...  
Keyword(s):  
Phase I ◽  
Hodgkin’S Lymphoma ◽  
Phase I Trial ◽  
Hodgkin's Lymphoma ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Non Hodgkin's Lymphoma ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

scholarly journals Phase I trial of recombinant human macrophage colony-stimulating factor in patients with invasive fungal infections

Blood ◽  
1991 ◽  
Vol 78 (4) ◽  
pp. 907-913 ◽  
Author(s):  
J Nemunaitis ◽  
JD Meyers ◽  
CD Buckner ◽  
K Shannon-Dorcy ◽  
M Mori ◽  
...  
Keyword(s):  
Phase I ◽  
Fungal Infections ◽  
Allogeneic Bone Marrow Transplantation ◽  
Marrow Transplant ◽  
Human Macrophage ◽  
Allogeneic Bone ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract A phase I dose escalation trial of recombinant human macrophage colony- stimulating factor (rhM-CSF) in combination with conventional antifungal therapy was conducted in 24 marrow transplant recipients with invasive fungal infection. Daily doses ranged from 100 to 2,000 micrograms/m2/d. Toxicity, such as constitutional symptoms, directly ascribed to rhM-CSF was not observed; however, transient, dose-related thrombocytopenia was observed. Patients who received 2,000 micrograms/m2/d of rhM-CSF had a mean reduction in platelet count of 61,000/mm3 during the rhM-CSF infusion period, which was significant when compared with patients who received lower doses of rhM-CSF (P = .008). Fourteen of the 16 patients who received rhM-CSF after undergoing allogeneic bone marrow transplantation had no change in the severity of graft-versus-host disease (GVHD) while receiving rhM-CSF. One had an increase in the severity of GVHD and one had a decrease. There were no effects on neutrophil, monocyte, or lymphocyte counts. Six patients had resolution of their infections, 12 were not evaluable for response, and six did not respond. Ten patients survived 100 days after initiation of rhM-CSF and 14 died. Further trials with rhM-CSF to assess antifungal activity are indicated.

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