scholarly journals Maintenance treatment of patients with myelodysplastic syndromes using recombinant human granulocyte colony-stimulating factor

Blood ◽  
1990 ◽  
Vol 76 (1) ◽  
pp. 36-43 ◽  
Author(s):  
RS Negrin ◽  
DH Haeuber ◽  
A Nagler ◽  
Y Kobayashi ◽  
J Sklar ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Myelodysplastic Syndromes ◽  
Red Blood Cell Transfusion ◽  
Granulocyte Colony Stimulating Factor ◽  
Risk Of Infection ◽  
Colony Stimulating Factor ◽  
Transfusion Requirements ◽  
Increased Risk ◽  
Stimulating Factor

Myelodysplastic syndromes (MDS) are characterized by chronic refractory cytopenias resulting in increased risk of infection, bleeding, and conversion to acute leukemia. In an effort to improve these cytopenias we have treated 18 patients over a 6- to 8-week period with increasing daily subcutaneous doses of recombinant human granulocyte colony- stimulating factor (G-CSF). Sixteen patients responded with improvement in neutrophil counts. On cessation of treatment these counts returned to baseline values over a 2- to 4-week period. To maintain these improved blood counts 11 patients were treated with G-CSF for more prolonged periods. Ten patients again responded with an increase in total leukocyte counts (1.6- to 6.4-fold) and absolute neutrophil counts (ANC) (3.6- to 16.3-fold), with responses persisting for 3 to 16 months. A significantly decreased risk of developing bacterial infections was noted during periods with ANC greater than 1,500/mm3 as compared with periods of time with ANC less than 1,500/mm3. Two anemic patients had a greater than 20% rise in hematocrit over the study period, and 2 additional patients had a decrease in red blood cell transfusion requirements during G-CSF treatment. Bone marrow myeloid maturation improved in 7 of 9 maintenance phase patients. Three patients progressed to acute myeloid leukemia during treatment. The drug was generally well-tolerated and no severe toxicities were noted. These data demonstrated that G-CSF administered to MDS patients by daily subcutaneous administration was well-tolerated and effective in causing persistent improvement of the neutrophil levels and marrow myeloid maturation. These effects were associated with a decreased risk of infection and, in some patients, with decreased red blood cell transfusion requirements.

Maintenance treatment of patients with myelodysplastic syndromes using recombinant human granulocyte colony-stimulating factor

Blood ◽  
1990 ◽  
Vol 76 (1) ◽  
pp. 36-43 ◽  
Author(s):  
RS Negrin ◽  
DH Haeuber ◽  
A Nagler ◽  
Y Kobayashi ◽  
J Sklar ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Myelodysplastic Syndromes ◽  
Red Blood Cell Transfusion ◽  
Granulocyte Colony Stimulating Factor ◽  
Risk Of Infection ◽  
Colony Stimulating Factor ◽  
Transfusion Requirements ◽  
Increased Risk ◽  
Stimulating Factor

Abstract Myelodysplastic syndromes (MDS) are characterized by chronic refractory cytopenias resulting in increased risk of infection, bleeding, and conversion to acute leukemia. In an effort to improve these cytopenias we have treated 18 patients over a 6- to 8-week period with increasing daily subcutaneous doses of recombinant human granulocyte colony- stimulating factor (G-CSF). Sixteen patients responded with improvement in neutrophil counts. On cessation of treatment these counts returned to baseline values over a 2- to 4-week period. To maintain these improved blood counts 11 patients were treated with G-CSF for more prolonged periods. Ten patients again responded with an increase in total leukocyte counts (1.6- to 6.4-fold) and absolute neutrophil counts (ANC) (3.6- to 16.3-fold), with responses persisting for 3 to 16 months. A significantly decreased risk of developing bacterial infections was noted during periods with ANC greater than 1,500/mm3 as compared with periods of time with ANC less than 1,500/mm3. Two anemic patients had a greater than 20% rise in hematocrit over the study period, and 2 additional patients had a decrease in red blood cell transfusion requirements during G-CSF treatment. Bone marrow myeloid maturation improved in 7 of 9 maintenance phase patients. Three patients progressed to acute myeloid leukemia during treatment. The drug was generally well-tolerated and no severe toxicities were noted. These data demonstrated that G-CSF administered to MDS patients by daily subcutaneous administration was well-tolerated and effective in causing persistent improvement of the neutrophil levels and marrow myeloid maturation. These effects were associated with a decreased risk of infection and, in some patients, with decreased red blood cell transfusion requirements.

scholarly journals Prolonged administration of granulocyte colony-stimulating factor (filgrastim) to patients with Fanconi anemia: a pilot study

Blood ◽  
1996 ◽  
Vol 88 (5) ◽  
pp. 1588-1593 ◽  
Author(s):  
WR Rackoff ◽  
A Orazi ◽  
CA Robinson ◽  
RJ Cooper ◽  
BP Alter ◽  
...  
Keyword(s):  
Blood Cell ◽  
Fanconi Anemia ◽  
Red Blood Cell ◽  
Hemoglobin Level ◽  
Red Blood Cell Transfusion ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Prolonged Administration ◽  
Cd34 Cells ◽  
Stimulating Factor

Abstract This report examines the effect of filgrastim (granulocyte colony- stimulating factor, [G-CSF] in 12 patients with neutropenia [absolute neutrophil count [ANC] < 1,000/mm3]) caused by Fanconi anemia (FA). Two of 14 patients who were evaluated for study entry were ineligible because of unsuspected cytogenetic abnormalities in their bone marrow (BM). G-CSF was started at 5 micrograms/kg/d. All patients had an increase in their ANC at week 8 (mean increase = 15,664/mm3). The median ANC during therapy was 5,030/mm3. Eight of 10 patients who completed 40 weeks on study maintained an ANC > 1,500/mm3 on G-CSF given every-otherday. Four patients had an increase in their platelet count by week 8 without transfusion (maximum increase = 23,000 to 45,000/mm3); however, platelet counts fell toward baseline levels as the G-CSF dose was reduced. BM CFU-MK were increased at week 8 in three of four evaluable patients. Four patients who did not receive red blood cell transfusions had an increase in their hemoglobin level of at least 2.0 g/dL. A fifth patient had a red blood cell transfusion in week 2 and then had a similar increase in hemoglobin level without subsequent transfusion. Eight of 10 patients who completed 40 weeks of treatment showed increases in the percentage of BM CD34+ cells measured by flow cytometry. The same proportion showed increases in peripheral blood CD34+ cells. Increased BM cellularity and myeloid hyperplasia were constant findings and were associated with increased expression of the proliferating cell nuclear antigen. Adverse experiences were mild fever (1 patient) and a new BM cytogenetic abnormality at week 40 (1 patient). This study shows that prolonged administration of G-CSF exerts a stimulatory effect on the BM of FA patients and may be used to maintain a clinically adequate ANC in these patients. G-CSF has beneficial effects on multiple hematopoietic lineages in some patients and may be a good candidate for use in combination cytokine protocols for FA patients with progressive aplastic anemia. G-CSF use results in an increase in circulating CD34+ cells, a finding with important implications for future gene transfer protocols.

scholarly journals Prolonged administration of granulocyte colony-stimulating factor (filgrastim) to patients with Fanconi anemia: a pilot study

Blood ◽  
1996 ◽  
Vol 88 (5) ◽  
pp. 1588-1593 ◽  
Author(s):  
WR Rackoff ◽  
A Orazi ◽  
CA Robinson ◽  
RJ Cooper ◽  
BP Alter ◽  
...  
Keyword(s):  
Blood Cell ◽  
Fanconi Anemia ◽  
Red Blood Cell ◽  
Hemoglobin Level ◽  
Red Blood Cell Transfusion ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Prolonged Administration ◽  
Cd34 Cells ◽  
Stimulating Factor

This report examines the effect of filgrastim (granulocyte colony- stimulating factor, [G-CSF] in 12 patients with neutropenia [absolute neutrophil count [ANC] < 1,000/mm3]) caused by Fanconi anemia (FA). Two of 14 patients who were evaluated for study entry were ineligible because of unsuspected cytogenetic abnormalities in their bone marrow (BM). G-CSF was started at 5 micrograms/kg/d. All patients had an increase in their ANC at week 8 (mean increase = 15,664/mm3). The median ANC during therapy was 5,030/mm3. Eight of 10 patients who completed 40 weeks on study maintained an ANC > 1,500/mm3 on G-CSF given every-otherday. Four patients had an increase in their platelet count by week 8 without transfusion (maximum increase = 23,000 to 45,000/mm3); however, platelet counts fell toward baseline levels as the G-CSF dose was reduced. BM CFU-MK were increased at week 8 in three of four evaluable patients. Four patients who did not receive red blood cell transfusions had an increase in their hemoglobin level of at least 2.0 g/dL. A fifth patient had a red blood cell transfusion in week 2 and then had a similar increase in hemoglobin level without subsequent transfusion. Eight of 10 patients who completed 40 weeks of treatment showed increases in the percentage of BM CD34+ cells measured by flow cytometry. The same proportion showed increases in peripheral blood CD34+ cells. Increased BM cellularity and myeloid hyperplasia were constant findings and were associated with increased expression of the proliferating cell nuclear antigen. Adverse experiences were mild fever (1 patient) and a new BM cytogenetic abnormality at week 40 (1 patient). This study shows that prolonged administration of G-CSF exerts a stimulatory effect on the BM of FA patients and may be used to maintain a clinically adequate ANC in these patients. G-CSF has beneficial effects on multiple hematopoietic lineages in some patients and may be a good candidate for use in combination cytokine protocols for FA patients with progressive aplastic anemia. G-CSF use results in an increase in circulating CD34+ cells, a finding with important implications for future gene transfer protocols.

scholarly journals Maintenance treatment of the anemia of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor and erythropoietin: evidence for in vivo synergy

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4076-4081 ◽  
Author(s):  
RS Negrin ◽  
R Stein ◽  
K Doherty ◽  
J Cornwell ◽  
J Vardiman ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Maintenance Phase ◽  
Infectious Complications ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Erythroid Response ◽  
Transfusion Requirements ◽  
Stimulating Factor

Patients with myelodysplastic syndromes (MDS) have refractory cytopenias leading to transfusion requirements and infectious complications. In vitro marrow culture data have indicated that granulocyte colony stimulating factor (G-CSF) synergizes with erythropoietin (EPO) for the production of erythroid precursors. In an effort to treat the anemia and neutropenia in this disorder, MDS patients were treated with a combination of recombinant human EPO and recombinant human G-CSF. Fifty-five patients were enrolled in the study of which 53 (96%) had a neutrophil response. Forty-four patients were evaluable for an erythroid response of which 21 (48%) responded. An erythroid response was significantly more likely in those patients with relatively low serum EPO levels, higher absolute basal reticulocyte counts and normal cytogenetics at study entry. Seventeen (81%) of the patients who responded to combined G-CSF plus EPO therapy continued to respond during an 8-week maintenance phase. G-CSF was then discontinued and all patients' neutrophil responses were diminished, whereas 8 continued to have an erythroid response to EPO alone. In 7 of the remaining 9 patients, resumption of G-CSF was required for recurrent erythroid responses. The median duration of erythroid responses to these cytokines was 11 months, with 6 patients having relatively prolonged and durable responses for 15 to 36 months. Our results also indicate that approximately one half of responding patients require both G-CSF and EPO to maintain an effective erythroid response, suggesting that synergy between G-CSF and EPO exists in vivo for the production of red blood cells in MDS.

scholarly journals A randomized study of erythropoietin and granulocyte colony-stimulating factor (G-CSF) versus placebo and G-CSF for patients with Hodgkin's and non-Hodgkin's lymphoma undergoing autologous bone marrow transplantation

Blood ◽  
1994 ◽  
Vol 83 (10) ◽  
pp. 2823-2828 ◽  
Author(s):  
NJ Chao ◽  
JR Schriber ◽  
GD Long ◽  
RS Negrin ◽  
M Catolico ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Red Blood Cell Transfusions ◽  
Autologous Bone ◽  
Stimulating Factor

Abstract Anemia is a universal finding in patients undergoing autologous bone marrow transplantation (BMT). Effective therapies to increase the number of autologous red blood cells could result in a lower morbidity and mortality associated with red blood cell transfusions. We examined whether the addition of erythropoietin (Epo) to intensive therapy supported by progenitor cell transplantation and granulocyte colony- stimulating factor (G-CSF) would result in a lower requirement for red blood cell transfusions. Thirty-five patients with lymphoma were randomized to receive Epo versus placebo. Epo (600 U/kg three times per week) or placebo was begun 3 weeks before administration of high-dose therapy. Epo was held during the week of the preparatory regimen, and restarted on the day after BMT. All patients also received G-CSF following BMT. No significant differences were noted between the two groups in terms of patient characteristics at pretreatment or post-BMT evaluation. There were no differences in the total number of red blood cell units transfused (median Epo: 8 v placebo: 6, P = .22) nor the number of platelet transfusions given (median Epo: 12 v placebo 5, P = .14). Engraftment of granulocytes (absolute neutrophil count > or = 500/microL) occurred in a median of 12 days (range, 9 to 33) for the patients receiving Epo and G-CSF, compared with a median of 10 days (range, 8 to 22) for those receiving placebo and G-CSF (P = .70). Likewise, there were no differences in the time to platelet count > or = 20,000/microL without further transfusions with a median of 22 days (range, 15 to 150+) for those receiving Epo and G-CSF compared with a median of 20 days (range, 11 to 54) for those patients receiving placebo and G-CSF (P = .28). The combination of G-CSF and Epo as administered in this study appears to be safe but does not result in an improvement in the total number of red blood cell transfusions or total number of single donor platelet units transfused.

scholarly journals Recombinant human granulocyte colony-stimulating factor increases circulating burst forming unit-erythron and red blood cell production in patients with severe human immunodeficiency virus infection

Blood ◽  
1990 ◽  
Vol 75 (11) ◽  
pp. 2137-2142 ◽  
Author(s):  
SA Miles ◽  
RT Mitsuyasu ◽  
K Lee ◽  
J Moreno ◽  
K Alton ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Binding Capacity ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Erythroid Progenitors ◽  
Humoral Factors ◽  
Immunodeficiency Virus ◽  
Stimulating Factor

Erythropoietin (EPO) is a major regulatory factor controlling red blood cell (RBC) production in humans. Although other humoral factors can alter the proliferation of committed early erythroid progenitors in vitro, no factor other than EPO has been clearly shown to induce proliferation of these cells in vivo. In a clinical trail of recombinant granulocyte colony-stimulating factor (G-CSF) and recombinant EPO in patients with advanced human immunodeficiency virus (HIV) infection, we noted reticulocytosis and increases in hemoglobin when G-CSF was administered before the administration of EPO. Subsequent studies demonstrated a significant increase in circulating burst forming unit-erythron (BFU-E) during daily recombinant G-CSF therapy. This increase was both time- and dose-dependent. The magnitude of increase in BFU-E correlated with the magnitude of increase in neutrophils and was associated with a mean increase in reticulocytes of 32,363/microL and a significant increase in mean hemoglobin of 1.04 +/- 0.34 g/dL over an 18-day interval. There was a significant increase in iron binding capacity and decreases in iron saturation and ferritin levels. In patients who were not recently transfused, there was an associated fall in endogenous erythropoietin levels. The increase in RBC production was most marked in patients who were severely anemic, transfusion-dependent, and who had elevated pretreatment EPO levels. There was no correlation between the increase in BFU-E and endogenous EPO levels or the time since last dose of zidovudine. The addition of recombinant EPO therapy three times weekly to patients did not result in further significant increases in BFU-E but did significantly increase hemoglobin. Our data suggest that recombinant G-CSF may be one of the hematopoietic factors that influences production of BFU-E and RBCs in humans.

scholarly journals Recombinant human granulocyte colony-stimulating factor increases circulating burst forming unit-erythron and red blood cell production in patients with severe human immunodeficiency virus infection

Blood ◽  
1990 ◽  
Vol 75 (11) ◽  
pp. 2137-2142 ◽  
Author(s):  
SA Miles ◽  
RT Mitsuyasu ◽  
K Lee ◽  
J Moreno ◽  
K Alton ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Binding Capacity ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Erythroid Progenitors ◽  
Humoral Factors ◽  
Immunodeficiency Virus ◽  
Stimulating Factor

Abstract Erythropoietin (EPO) is a major regulatory factor controlling red blood cell (RBC) production in humans. Although other humoral factors can alter the proliferation of committed early erythroid progenitors in vitro, no factor other than EPO has been clearly shown to induce proliferation of these cells in vivo. In a clinical trail of recombinant granulocyte colony-stimulating factor (G-CSF) and recombinant EPO in patients with advanced human immunodeficiency virus (HIV) infection, we noted reticulocytosis and increases in hemoglobin when G-CSF was administered before the administration of EPO. Subsequent studies demonstrated a significant increase in circulating burst forming unit-erythron (BFU-E) during daily recombinant G-CSF therapy. This increase was both time- and dose-dependent. The magnitude of increase in BFU-E correlated with the magnitude of increase in neutrophils and was associated with a mean increase in reticulocytes of 32,363/microL and a significant increase in mean hemoglobin of 1.04 +/- 0.34 g/dL over an 18-day interval. There was a significant increase in iron binding capacity and decreases in iron saturation and ferritin levels. In patients who were not recently transfused, there was an associated fall in endogenous erythropoietin levels. The increase in RBC production was most marked in patients who were severely anemic, transfusion-dependent, and who had elevated pretreatment EPO levels. There was no correlation between the increase in BFU-E and endogenous EPO levels or the time since last dose of zidovudine. The addition of recombinant EPO therapy three times weekly to patients did not result in further significant increases in BFU-E but did significantly increase hemoglobin. Our data suggest that recombinant G-CSF may be one of the hematopoietic factors that influences production of BFU-E and RBCs in humans.

Sign in / Sign up

Export Citation Format

Share Document