A phase II trial of recombinant human granulocyte colony‐stimulating factor in the myelodysplastic syndromes

Abstract

We conducted a phase II study of the intravenous administration of a glycosylated recombinant human granulocyte colony-stimulating factor (rhG-CSF) for 7-14 d in 41 patients with the myelodysplastic syndromes (MDS). Administration of rhG-CSF elicited striking rises in both leucocyte and neutrophil counts in the majority of the patients irrespective of the FAB subtypes of MDS. The rises in neutrophil counts were dose dependent and 5 micrograms/kg/d of rhG-CSF yielded approximately an 8-fold increase in neutrophil counts. Leucocytes and neutrophil counts started to increase shortly after the first injection of 5 micrograms/kg, was maintained at significantly elevated levels during 14 d of treatment, and returned to the pretreatment levels within several days following discontinuation of rhG-CSF. The action of rhG-CSF was specific for neutrophils since leucocytosis was due exclusively to neutrophilic increase associated with an increased marrow myeloid maturation. There were no consistent changes in the monocyte, eosinophil, lymphocyte, platelet or reticulocyte counts. After treatment, the percentage of marrow blast cells was reduced in eight of 13 evaluable patients with refractory anaemia with an excess of blasts (RAEB) or RAEB in transformation (RAEB-t). No patients developed acute leukaemia during the treatment or in the immediate follow-up period. The treatment was well tolerated with only minimal toxicity. The results suggest that rhG-CSF is a safe and effective way to promptly improve neutropenia in MDS patients.

Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial

“…Granulocytecolony-stimulating factor (G-CSF) and granulocyte macrophagecolony-stimulating factor (GM-CSF) increase neutrophil counts, do not increase the risk for leukemia, and have no effect on survival. [2][3][4] When combined with myeloid cytokines, rHuEPO can have synergistic effects on erythropoiesis in vitro. 5,6 Some clinical studies have shown that the combination of rHuG-CSF and rHuEPO has a better response rate (40%-50%) than rHuEPO alone.…”

Revisiting Use of Growth Factors in Myelodysplastic Syndromes

“…The majority of MDS patients with neutropenia respond to G-CSF (Kobayashi et al, 1989;Yoshida et al, 1991;Kaczmarski et al, 1993;.…”

“…It has been suggested that rHuG-CSF should be considered when there is no response to EPO after 6-8 weeks of therapy (Steensma et al, 2006). It has not been shown yet that rhG-CSF alone can improve survival in MDS patients (Kobayashi et al, 1989;Negrin et al, 1989;Ohyashuki et al, 1989;Negrin et al, 1990;Yoshida et al, 1991;Kaczmarski 1993). In association with a hypomethylating agent or lenalidomide or in case of severe infection, G-CSF can be used for the management of neutropenia after chemotherapy.…”

Acute Myelogenous Leukemia with a t(2;17;4)(p13;q21;p16) Aberration: Effective Treatment with All-Trans Retinoic Acid and Granulocyte Colony-Stimulating Factor.

“…The gene coding granulocyte colonystimulating factor (G-CSF) is located on chromosome 17ql 1.2 to 21, proximal to the breakpoint oft(15;17) in APL (8). During treatment with G-CSF, an increase in neutrophil counts is observed in patients with MDS, and in someof these patients increases in reticulocytes, and platelets counts have also been found (9,10). ATRAshows a synergistic effect with G-CSFon several leukemia cells in vitro (1 1).…”