Treatment of Myelodysplastic Syndrome With Low-Dose Human Granulocyte Colony-Stimulating Factor: A Multicenter Study

Abstract

The objective of this study was to determine the hematopoietic effects and toxicity of low-dose granulocyte colony-stimulating factor (G-CSF) in myelodysplastic syndrome (MDS) patients with neutropenia. Recombinant human G-CSF (Lenograstim) was administered by daily subcutaneous injection with an initial dosage of 0.5 microg/kg per day for 2 weeks. Patients not responding to the initial dosage received the escalated dosage, 1 to 2 microg/kg per day for 2 weeks. Eligibility criteria were the following: French-American-British disease classification subtype refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), or refractory anemia with excess blasts (RAEB) with an absolute neutrophil count (ANC) of <1.5 x 10(9)/L. Criteria indicating response to treatment were ANC of >1.5 x 10(9)/L and doubling of ANC on at least 2 occasions. Thirty-two MDS patients were recruited from 6 university hospitals. Eighteen patients had RA, 4 had RARS, and 10 had RAEB. Median age was 56.4 years (range, 28-87 years). Twenty-six patients (81.2%) had an increase in ANC from a median of 0.94+/-0.35 x 10(9)/L to 4.24+/-3.78 x 10(9)/L. Three of 6 patients who did not respond to the initial dosage responded to the escalated dosage of 1 microg/kg per day. Eighteen (81.8%) of 22 patients with RA or RARS responded compared with 8 (80%) of 10 patients with RAEB. The response rates in patients with ANCs of <0.5 x 10(9)/L. 0.5 to <1.0 x 10(9)/L, and 1.0 to 1.5 x 10(9)/L were 80%, 70%, and 88.2%, respectively. The side effects were minimal. No significant changes in hemoglobin levels or platelet counts were observed. In conclusion, low-dose G-CSF administered by subcutaneous injection is well tolerated and effective in improving neutropenia in MDS patients.

Infectious complications in patients with myelodysplastic syndromes: A review of the literature with emphasis on patients treated with 5‐azacitidine

“…In most of the trials, treatment with G-CSF let to increased ANC. [42][43][44][45][46] However, none of the trials could demonstrate improvement in overall survival. Moreover, the effect of G-CSF on malignant clones remains unclear, with studies reporting preferential stimulation of, for example, monosomy seven clones while others do not.…”

“…Several trials have investigated the role of granulocytic growth factors in patients with MDS. In most of the trials, treatment with G‐CSF let to increased ANC . However, none of the trials could demonstrate improvement in overall survival.…”

Haemopoietic growth factors in the treatment of myelodysplastic syndrome

“…These growth factors have acceptable toxicity without significant stimulation of leukaemic myelopoiesis or subsequent progression into AML, as demonstrated in controlled studies [52][53][54][55][56].…”

“…Association of EPO and G-CSF determinate a response rate of ∼ 40 -60% in the lowest risk MDS [69]. In addition, G-CSF is effective in increasing peripheral neutrophil counts and reduces infections in MDS with acceptable toxicity without significant stimulation of leukaemic myelopoiesis [49][50][51][52][53][54][55][56]. The options are more limited for an HGF-based treatment of thrombocytopenia: recombinant IL-11 is actually the only FDA approved drug for the prevention of the severe thrombocytopenia after myelosuppressive chemotherapy [69].…”