scholarly journals Long-term follow-up of patients with invasive fungal disease who received adjunctive therapy with recombinant human macrophage colony- stimulating factor

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1422-1427 ◽  
Author(s):  
J Nemunaitis ◽  
K Shannon-Dorcy ◽  
FR Appelbaum ◽  
J Meyers ◽  
A Owens ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Adjunctive Therapy ◽  
Human Macrophage ◽  
Colony Stimulating Factor ◽  
Long Term Follow Up ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Mortality of bone marrow transplant (BMT) patients who develop invasive fungal infection is greater than 80%. Long-term follow-up of 46 consecutive BMT patients who received recombinant human macrophage colony-stimulating factor (rhM-CSF) as adjunctive therapy with standard antifungal treatment who were entered into phase I/II trials at The Fred Hutchinson Cancer Research Center is reported. rhM-CSF (100 micrograms/m2 to 2,000 micrograms/m2; Chiron/Cetus Corporation, Emeryville, CA) was administered from day 0 to 28 after determination of progressive fungal disease. Results of long-term follow-up of fungal infection, relapse, and survival were compared with 58 similar historical controls. Multivariable analysis of the patients who received rhM-CSF showed two factors that significantly correlated with poor survival: Karnofsky score < or = 20% and Aspergillus infection. Overall, survival of patients who received rhM-CSF was greater than that of historical patients (27% v 5%) and was entirely because of a 50% survival rate in patients with Candida infection and Karnofsky scores greater than 20%. Prospective, randomized, controlled trials to determine efficiency of rhM-CSF are indicated and should be directed at patients with invasive candidiasis.

scholarly journals Long-term follow-up of patients with invasive fungal disease who received adjunctive therapy with recombinant human macrophage colony- stimulating factor

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1422-1427
Author(s):  
J Nemunaitis ◽  
K Shannon-Dorcy ◽  
FR Appelbaum ◽  
J Meyers ◽  
A Owens ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Adjunctive Therapy ◽  
Human Macrophage ◽  
Colony Stimulating Factor ◽  
Long Term Follow Up ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Mortality of bone marrow transplant (BMT) patients who develop invasive fungal infection is greater than 80%. Long-term follow-up of 46 consecutive BMT patients who received recombinant human macrophage colony-stimulating factor (rhM-CSF) as adjunctive therapy with standard antifungal treatment who were entered into phase I/II trials at The Fred Hutchinson Cancer Research Center is reported. rhM-CSF (100 micrograms/m2 to 2,000 micrograms/m2; Chiron/Cetus Corporation, Emeryville, CA) was administered from day 0 to 28 after determination of progressive fungal disease. Results of long-term follow-up of fungal infection, relapse, and survival were compared with 58 similar historical controls. Multivariable analysis of the patients who received rhM-CSF showed two factors that significantly correlated with poor survival: Karnofsky score < or = 20% and Aspergillus infection. Overall, survival of patients who received rhM-CSF was greater than that of historical patients (27% v 5%) and was entirely because of a 50% survival rate in patients with Candida infection and Karnofsky scores greater than 20%. Prospective, randomized, controlled trials to determine efficiency of rhM-CSF are indicated and should be directed at patients with invasive candidiasis.

scholarly journals Inhibition of hematopoiesis in normal human long-term marrow cultures treated with recombinant human macrophage colony-stimulating factor

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 651-657 ◽  
Author(s):  
H Mayani ◽  
LJ Guilbert ◽  
SC Clark ◽  
A Janowska-Wieczorek
Keyword(s):  
Inhibitory Activity ◽  
Inhibitory Effect ◽  
Human Macrophage ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Stromal Layer ◽  
Marrow Cultures

Abstract The effects of recombinant human macrophage colony-stimulating factor (rhCSF-1) in long-term marrow cultures (LTMC) established from normal bone marrow cells were examined. When added during the first 3 weeks of culture (every second day, at 15 ng/mL), rhCSF-1 strongly inhibited the growth of all hematopoietic progenitors analyzed (colony-forming unit- MIX [CFU-MIX], CFU-granulocyte macrophage [CFU-GM], CFU-M, CFU-G, burst- forming unit-erythroid). Paralleling the inhibition of progenitors was the complete loss of adipocytes from the stromal layer of rhCSF-1- treated cultures. The inhibitory effect of rhCSF-1 correlated in all instances with the accumulation in the supernatants of these cultures of an activity (different from CSF-1) that inhibited colony formation in semisolid cultures. When addition of rhCSF-1 was delayed 3 weeks, its inhibitory effects were significantly reduced, which correlated with reduced inhibitory activity detected in the supernatants. Analysis of CSF-1 concentration by radioreceptor assay confirmed that added rhCSF-1 increased culture CSF-1 levels and showed that the decreased inhibition observed when rhCSF-1 is added later in culture was not due to decreased CSF-1 levels at that point. In contrast, the ability of rhCSF-1 to inhibit hematopoiesis and accumulate inhibitory activity in LTMC correlated with its rate of utilization, much higher in the first 2 weeks of culture, when the stromal layer was being established, than later. These observations document the inhibitory effect of rhCSF-1 on all aspects of hematopoiesis conducted in cultures that simulate the hematopoietic microenvironment, demonstrate the importance of accessory/stromal cells in mediating the effects of rhCSF-1 in LTMC, and point to an inhibitory activity as the mediating agent.

scholarly journals Long-term follow-up of a phase III study of recombinant human granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid malignancies

Blood ◽  
1993 ◽  
Vol 81 (7) ◽  
pp. 1903-1908
Author(s):  
SN Rabinowe ◽  
D Neuberg ◽  
PJ Bierman ◽  
JM Vose ◽  
J Nemunaitis ◽  
...  
Keyword(s):  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Phase Iii ◽  
Long Term Follow Up ◽  
Macrophage Colony Stimulating Factor ◽  
Autologous Bone ◽  
Macrophage Colony ◽  
Stimulating Factor

One hundred and twenty-eight patients with non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), and acute lymphoblastic leukemia (ALL) previously reported from a phase III trial of rhGM-CSF or placebo following autologous bone marrow transplantation (ABMT) were investigated for the development of late toxicities. Median follow-up is 36 months. No apparent long-term deleterious effects on BM function were observed. Moreover, disease-free survival and overall survival were similar for patients on both treatment arms, arguing for the long- term safety of recombinant human granulocyte macrophage-colony- stimulating factor (rhGM-CSF). The only factors predictive for both a high risk of relapse over time and mortality were having the diagnosis of ALL and/or undergoing ABMT in resistant relapse. We attempted to identify clinical variables before BM harvest, at the time of marrow infusion, or events within the first 100 days posttransplant, which might predict speed of neutrophil recovery in the setting of placebo or rhGM-CSF administration after ABMT. Only previous exposure to agents that deplete stem cells led to a significant delay in neutrophil recovery, suggesting their avoidance in patients who may undergo ABMT. Nevertheless, even those patients benefited from rhGM-CSF. For all patients, rhGM-CSF and agents that deplete stem cells were the strongest independent predictors for neutrophil engraftment. With the increasing use of newer hematopoietic growth factors both alone and in combination, long-term follow-up is essential to confirm the same safety that we report with rhGM-CSF.

scholarly journals Protective Effect of Human Macrophage Colony-Stimulating Factor on Fungal Infection (2)

1995 ◽  
Vol 69 (5) ◽  
pp. 582-589 ◽  
Author(s):  
Hideyuki FUJITA ◽  
Hirotoshi MASUDA ◽  
Tsunetaka NAKAJIMA ◽  
Koji YADA ◽  
Masahiro WATANABE ◽  
...  
Keyword(s):  
Protective Effect ◽  
Fungal Infection ◽  
Human Macrophage ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

scholarly journals Protective Effect of Human Macrophage Colony-Stimulating Factor (hM-CSF) on Fungal Infection (1)

1995 ◽  
Vol 69 (1) ◽  
pp. 60-67 ◽  
Author(s):  
Hideyuki FUJITA ◽  
Hirotoshi MASUDA ◽  
Tsunetaka NAKAJIMA ◽  
Takashi NAKAE ◽  
Yuji NARITA ◽  
...  
Keyword(s):  
Protective Effect ◽  
Fungal Infection ◽  
Human Macrophage ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

scholarly journals Inhibition of hematopoiesis in normal human long-term marrow cultures treated with recombinant human macrophage colony-stimulating factor

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 651-657
Author(s):  
H Mayani ◽  
LJ Guilbert ◽  
SC Clark ◽  
A Janowska-Wieczorek
Keyword(s):  
Inhibitory Activity ◽  
Inhibitory Effect ◽  
Human Macrophage ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Stromal Layer ◽  
Marrow Cultures

The effects of recombinant human macrophage colony-stimulating factor (rhCSF-1) in long-term marrow cultures (LTMC) established from normal bone marrow cells were examined. When added during the first 3 weeks of culture (every second day, at 15 ng/mL), rhCSF-1 strongly inhibited the growth of all hematopoietic progenitors analyzed (colony-forming unit- MIX [CFU-MIX], CFU-granulocyte macrophage [CFU-GM], CFU-M, CFU-G, burst- forming unit-erythroid). Paralleling the inhibition of progenitors was the complete loss of adipocytes from the stromal layer of rhCSF-1- treated cultures. The inhibitory effect of rhCSF-1 correlated in all instances with the accumulation in the supernatants of these cultures of an activity (different from CSF-1) that inhibited colony formation in semisolid cultures. When addition of rhCSF-1 was delayed 3 weeks, its inhibitory effects were significantly reduced, which correlated with reduced inhibitory activity detected in the supernatants. Analysis of CSF-1 concentration by radioreceptor assay confirmed that added rhCSF-1 increased culture CSF-1 levels and showed that the decreased inhibition observed when rhCSF-1 is added later in culture was not due to decreased CSF-1 levels at that point. In contrast, the ability of rhCSF-1 to inhibit hematopoiesis and accumulate inhibitory activity in LTMC correlated with its rate of utilization, much higher in the first 2 weeks of culture, when the stromal layer was being established, than later. These observations document the inhibitory effect of rhCSF-1 on all aspects of hematopoiesis conducted in cultures that simulate the hematopoietic microenvironment, demonstrate the importance of accessory/stromal cells in mediating the effects of rhCSF-1 in LTMC, and point to an inhibitory activity as the mediating agent.

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