Granulocyte colony-stimulating factor accelerates neutrophil engraftment following peripheral-blood stem-cell transplantation: a prospective, randomized trial.

1995 ◽  
Vol 13 (6) ◽  
pp. 1323-1327 ◽  
Author(s):  
T R Klumpp ◽  
K F Mangan ◽  
S L Goldberg ◽  
E S Pearlman ◽  
J S Macdonald
Keyword(s):  
Bone Marrow ◽  
Autologous Bone Marrow ◽  
High Dose ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Autologous Bone ◽  
Stimulating Factor ◽  
Neutrophil Engraftment

PURPOSE It is well-established that the infusion of hematopoietic growth factors (HGF) accelerates neutrophil recovery in patients undergoing high-dose therapy followed by autologous bone marrow infusion. In addition, there is evidence that the infusion of autologous peripheral-blood stem cells (PBSC) accelerates engraftment in comparison to patients who receive bone marrow alone. However, few data are available regarding the ability of HGF to accelerate engraftment further in patients who receive PBSC following high-dose therapy. PATIENTS AND METHODS Forty-one patients undergoing high-dose therapy followed by infusion of autologous PBSC with or without bone marrow were randomized to receive granulocyte colony-stimulating factor (G-CSF) 5 micrograms/kg/d beginning on day + 1 following transplant or standard posttransplant supportive care without HGF. RESULTS The median time to a neutrophil count > or = 500/microL was 10.5 days in the G-CSF group versus 16 days in the control group (P = .0001). G-CSF was associated with statistically significant reductions in the time to neutrophil engraftment among patients who received PBSC alone (11 v 17 days, P = .0003) and in patients who received PBSC in conjunction with bone marrow (10 v 14 days, P = .02). The median duration of posttransplant hospitalization (18 v 24 days, P = .002) and the median number of days on nonprophylactic antibiotics (11 v 15, P = .03) were also significantly reduced. CONCLUSION Administration of G-CSF in the posttransplant period accelerates the rate of neutrophil engraftment, shortens the duration of hospitalization, and reduces the number of days on nonprophylactic antibiotics in patients who receive autologous PBSC with or without autologous bone marrow following high-dose therapy.

scholarly journals Characterization of endogenous cytokine concentrations after high-dose chemotherapy with autologous bone marrow support

Blood ◽  
1993 ◽  
Vol 81 (9) ◽  
pp. 2452-2459 ◽  
Author(s):  
J Rabinowitz ◽  
WP Petros ◽  
AR Stuart ◽  
WP Peters
Keyword(s):  
Bone Marrow ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
Tnf Alpha ◽  
High Dose ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Autologous Bone ◽  
Macrophage Colony ◽  
Stimulating Factor

Endogenous cytokines are thought to mediate numerous biologic processes and may account for some adverse effects experienced following the administration of recombinant proteins. This study describes the pattern of endogenous cytokine exposure following high-dose chemotherapy. Blood concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), macrophage colony-stimulating factor (M-CSF), and erythropoietin (EPO) were measured by enzyme-linked immunosorbent assay (ELISA) methods in 68 patients receiving the same ablative chemotherapy regimen (cyclophosphamide, cisplatin, carmustine). Patients were grouped according to cellular support (autologous bone marrow [BM] CSF-primed peripheral blood progenitor cells [PBPCs]) and prescribed growth factor (recombinant human granulocyte or granulocyte-macrophage colony-stimulating factor [rHuG- CSF or rHuGM-CSF]). Leukocyte reconstitution was most accelerated in the groups treated with PBPCs and rHuG-CSF. IL-6, M-CSF, and TNF-alpha concentrations were higher in the groups treated with rHuGM-CSF and without PBPCs. Maximal endogenous cytokine concentrations occurred approximately 12 days after BM reinfusion. High concentrations of EPO occurred in patients experiencing significant hypotension despite routine transfusions for hematocrit < 42%. High M-CSF and IL-6 levels were associated with increased platelet transfusion requirements. Concentrations of all four cytokines were significantly higher in patients experiencing renal or hepatic toxicity, with elevations occurring in a predictable sequence and M-CSF elevations occurring first. This report shows that endogenous cytokine concentrations may be influenced by either cellular or CSF support and are associated with differences in platelet reconstitution and organ toxicity.

scholarly journals A phase II study of continuous infusion recombinant human granulocyte- macrophage colony-stimulating factor as an adjunct to autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma in first remission

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2707-2714
Author(s):  
SJ O'Day ◽  
SN Rabinowe ◽  
D Neuberg ◽  
AS Freedman ◽  
RJ Soiffer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Colony Stimulating Factor ◽  
First Remission ◽  
Macrophage Colony Stimulating Factor ◽  
Autologous Bone ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Neutrophil Engraftment

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) clearly hastens myeloid recovery in patients with relapsed hematologic malignancies undergoing autologous bone marrow transplantation (ABMT). In efforts to further improve neutrophil engraftment and shorten hospital stay in ABMT patients, rhGM-CSF was administered by a potentially more potent route (continuous infusion) to non-Hodgkin's lymphoma (NHL) patients with better BM reserve (first remission). Time to myeloid engraftment was compared with that of NHL patients treated in first remission at our institution on a similar ABMT protocol but without growth factor support (controls). Median neutrophil engraftment (absolute neutrophil count, 500 cells/microL) in first remission patients treated with rhGM-CSF was 14 days, compared with 22 days in controls (P = .0001). Hospital stays were also significantly reduced for rhGM-CSF patients (P = .0003). Platelet engraftment did not differ between the two groups. Persistent fever and generalized serositis were the primary toxicities. rhGM-CSF, delivered by this route, was efficacious but more toxic than 2-hour rhGM-CSF infusions previously reported by other investigators. Future alterations in both dose and schedule may retain comparable efficacy yet diminish toxicity.

scholarly journals Characterization of endogenous cytokine concentrations after high-dose chemotherapy with autologous bone marrow support

Blood ◽  
1993 ◽  
Vol 81 (9) ◽  
pp. 2452-2459 ◽  
Author(s):  
J Rabinowitz ◽  
WP Petros ◽  
AR Stuart ◽  
WP Peters
Keyword(s):  
Bone Marrow ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
Tnf Alpha ◽  
High Dose ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Autologous Bone ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Endogenous cytokines are thought to mediate numerous biologic processes and may account for some adverse effects experienced following the administration of recombinant proteins. This study describes the pattern of endogenous cytokine exposure following high-dose chemotherapy. Blood concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), macrophage colony-stimulating factor (M-CSF), and erythropoietin (EPO) were measured by enzyme-linked immunosorbent assay (ELISA) methods in 68 patients receiving the same ablative chemotherapy regimen (cyclophosphamide, cisplatin, carmustine). Patients were grouped according to cellular support (autologous bone marrow [BM] CSF-primed peripheral blood progenitor cells [PBPCs]) and prescribed growth factor (recombinant human granulocyte or granulocyte-macrophage colony-stimulating factor [rHuG- CSF or rHuGM-CSF]). Leukocyte reconstitution was most accelerated in the groups treated with PBPCs and rHuG-CSF. IL-6, M-CSF, and TNF-alpha concentrations were higher in the groups treated with rHuGM-CSF and without PBPCs. Maximal endogenous cytokine concentrations occurred approximately 12 days after BM reinfusion. High concentrations of EPO occurred in patients experiencing significant hypotension despite routine transfusions for hematocrit < 42%. High M-CSF and IL-6 levels were associated with increased platelet transfusion requirements. Concentrations of all four cytokines were significantly higher in patients experiencing renal or hepatic toxicity, with elevations occurring in a predictable sequence and M-CSF elevations occurring first. This report shows that endogenous cytokine concentrations may be influenced by either cellular or CSF support and are associated with differences in platelet reconstitution and organ toxicity.

High-dose chemotherapy with autologous bone marrow transplantation in 50 advanced resistant Hodgkin's disease patients: an Italian study group report.

1988 ◽  
Vol 6 (9) ◽  
pp. 1411-1416 ◽  
Author(s):  
A M Carella ◽  
A M Congiu ◽  
E Gaozza ◽  
P Mazza ◽  
P Ricci ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Progressive Disease ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Autologous Bone

Fifty patients with recurrent Hodgkin's disease have been treated with high-dose therapy followed by autologous bone marrow transplantation. Forty-one patients had extranodal sites of relapse and 31 patients had constitutional symptoms. Two patients had been treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), lomustine, vinblastine, procarbazine, and prednisone (CcVPP), and radiation; 16 patients with MOPP, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), radiation, and lomustine, etoposide, and prednisone (CEP); 20 patients with alternating MOPP/ABVD, and 12 patients with alternating MOPP/ABVD followed by CEP and radiation. Eighteen patients had progressive disease during alternating MOPP/ABVD protocol alone or during conventional salvage therapy; 32 patients had had a complete remission with first-line therapy but later relapsed, 25 of them having received conventional salvage therapy; 12 achieved no response or progression ("resistant-relapse" patients); and 13 responded partially or completely ("sensitive-relapse" patients). Complete remission occurred in 24 patients (48%) with a median duration of 24 months and 16 patients (32%) achieved partial response with a median duration of 9 months, for an overall response rate of 80%. Ten patients failed to respond and died in progressive disease 1 to 10 months (median, 6 months) after transplantation. Toxicity was significant including infections (20%), liver enzymes and alkaline phosphatase elevations (100%), and carmustine lung toxicity (7%). There were two treatment-related deaths; one patient died of Pseudomonas aeruginosa septicemia and another patient died of cerebral hemorrhage. These results validate the procedure of high-dose therapy followed by autologous bone marrow transplantation in inducing remission in these advanced, highly-treated patients. Clearly, the question of whether high-dose therapy and transplantation will eventually supersede new conventional salvage therapies will be addressed after controlled clinical studies.

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