Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor in Patients with Myelodysplastic Syndromes – a Phase-I/II Trial

Abstract

In einer Phase-I/II-Studie wurde der therapeutische Effekt von rhGM-CSF bei Patienten mit myelodysplastischen Syndromen analysiert. 9 Patienten, für die keine anderen Therapiemöglichkeiten bestanden, erhielten rhGM-CSF in einer Dosierung von 15 μg/m² bis 150 μg/m² als 8stündige i.v.-Infusion für 7 Tage. Nach einem therapiefreien Intervall von 14 Tagen wurde der Therapiezyklus wiederholt. Dosisabhängig stiegen die Leukozyten bei 7 von 9 Patienten an, während die Throm-bozyten nur bei 1 Patienten anstiegen. Veränderungen der Retikulozyten wurden nicht beobachtet. rhGM-CSF wurde gut toleriert, Hauptnebenwirkungen waren leichte lokale Phlebitiden an der Infusions-stelle und Sternalschmerzen nach Bolusinjektion.

Antithymocyte globulin (ATG)-based therapy in patients with myelodysplastic syndromes

“…[4][5][6][7] Therapeutic options are limited. 8 Management strategies used in MDS include growth factors [9][10][11][12][13][14][15][16][17][18] and chemotherapy, [19][20][21] as well as supportive care with antibiotics and transfusions. 22 Allogeneic transplantation, although potentially curative, is a realistic option for only a small proportion of these patients due to patient age and the limited availability of appropriate donors.…”

Endogenous FLT-3 ligand serum levels are associated with disease stage in patients with myelodysplastic syndromes

“…As the majority of MDS patients do not die from acute leukemia but from the consequences of cytopenia, clinical trials have attempted to overcome cytopenia with the use of HGF, [5][6][7][8] despite the potential risk of stimulating the malignant clone. Although factors like G-CSF, 5 GM-CSF 6 or IL-3 7,8 were shown to improve cytopenia for the duration of treatment in a significant number of patients, success in general has been limited.…”

“…To date, no generally accepted treatment is available for MDS except allogeneic bone marrow transplantation. Although several clinical trials have attempted to overcome cytopenias by using hematopoietic growth factors (HGF), [5][6][7][8] success has been limited in part due to an insufficient under- standing of the role of HGF in the pathogenesis and the course of MDS. In the group of patients suffering from refractory anemia (RA) who were treated with G-CSF, 5 GM-CSF 6 or IL-3, 7,8 no increased rate of irreversible transition to overt leukemia occurred as compared to the natural course of the disease.…”

Myelodysplastic Syndromes and Growth Factors

“…In one series from Frankfurt, Germany, four of II patients did have an increase in bone marrow blasts in response to GM-CSF (7). Several other studies have not shown overt transition towards acute leukemia.…”