Treatment of anemia in low risk myelodysplastic syndromes with granulocyte–macrophage colony-stimulating factor plus recombinant human erythropoietin

Abstract

The aim of this prospective study was to determine whether treatment with a combination of GM-CSF and erythropoietin (rhEpo) can improve the anemia associated with low risk myelodysplastic syndrome (MDS), namely refractory anemia (RA), RA with ring sideroblasts (RAS), and RA with excess of blasts (RAEB) with bone marrow blasts less than 10%. Eligibility criteria included an Hb level of less than 10.5 g/dl for newly diagnosed patients, or symptomatic anemia. GM-CSF was given at a dose of 3 g/kg s.c. on days 1-2, rhEpo at a dose of 60 U/kg s.c. on days 3-5. No treatment was given on days 6-7. Patients were followed-up with full blood count on a weekly basis. The treatment was repeated for a total of 6 weeks. At that time, if a rise in Hb above 1.5 g/dl had not been achieved, the dose of rhEpo increased to 120 U/kg. Post-treatment evaluation was performed at the completion of 12 weeks. Erythroid response was defined as good (GR), if an increase in untransfused Hb values above 2 g/dl or a 100% decrease in red blood cell transfusion requirements, over the treatment period was observed, while an increase in untransfused Hb values 1-2 g/dl or a Ͼ50% decrease in transfusion requirements, were considered as partial response. Responders continued to receive the same treatment until disease progression. Nineteen patients (13 male and six female) with a median age of 69 years were enrolled in the study. The FAB subtypes were: RA one case, RAS eight cases and RAEB 10 cases. Ten of 19 patients (52.6%) responded to the treatment: 7/19 (36.8%) achieved a GR and 3/19 (15.8%) a PR. Six of eight (75%) patients with RAS, one case with RA and 3/10 (30%) of cases with RAEB responded to treatment. Pretreatment serum epo levels were generally low (less than 200 Mu/ml) in responding patients. At the completion of the initial 12 weeks, 8/12 responding patients (5 RAS, 2 RAEB and 1 RA) continued to receive the same treatment. All responding patients with RAS continued to show an erythroid response in a time period from 3 to 24 months, whilst one patient with RA and two with RAEB did not have a continuing response at 2, 4 and 12 months, respectively. The above data suggest that the combination of rhEpo and GM-CSF should be recommended in all cases with RARS. However, the clear indication of this combination for other patients with MDS remains to be determined.

Treatment of Anemia with Erythropoietic Agents in Patients with Hematologic Malignancies

“…[60][61][62][63][64][65][66][67][68][69][70][71][72] To date, there is no clear consensus on the most appropriate dosage regimens for these agents to correct anemia in this patient population. Dosage regimens used in many MDS trials have differed from those used in trials in patients with solid tumors or hematologic malignancies.…”

“…Dosage regimens used in many MDS trials have differed from those used in trials in patients with solid tumors or hematologic malignancies. [60][61][62][63]67,69,71 However, in several studies in MDS, dosage regimens similar to those employed in patients with solid tumors or hematologic malignancies appear to be effective in correcting anemia in this patient population. [64][65][66]68,70,72 Clinical endpoints used to evaluate the efficacy of erythropoietic agents in patients with MDS have also differed from those used in studies in patients with solid tumors or hematologic malignancies.…”

“…In studies of MDS, efficacy has been generally assessed by the proportion of patients with a major erythroid response (Hb increase ≥ 2 g/dL with no transfusions or a 100% decrease in transfusions) or a minor erythroid response (Hb increase of 1-2 g/dL with no transfusions or a ≥ 50% decrease in transfusions). 60,61,[63][64][65][66][67]69,70 Certain characteristics can predispose some patients with MDS to be unresponsive to erythropoietic therapy, including endogenous serum erythropoietin levels > 200 mU/L, the presence of bone marrow blasts, and requirement of transfusions before initiation of erythropoietic therapy. 60,65 Higher pretreatment levels of tumor necrosis factor-α may also be predictive of nonresponse.…”

Recombinant human erythropoietin in combined treatment with granulocyte- or granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes

“…In low-risk MDS Economopoulos (Economopoulos et al 1999) treated 19 patients with GM-CSF (3 lgAE kgAEday SC) on day 1 and 2, followed by EPO (60 U/ kgAEday) on days 3-5 and no treatment on day 6 and 7. This treatment was repeated for a period of 6 weeks after which the dose of EPO could be increased to 120 UAEkgAEday SC.…”

Recombinant human erythropoietin in the treatment of anemic patients with hematological malignancies

“…There are few trials demonstrating the efficiency of erythropoietin plus GM-CSF with response rates varying between 35% and 37% [31,99]. Recently, a randomized study was published that combined GM-CSF in a dose of 0.3-5.0 µg/kg per day and 150 U/kg erythropoietin three times a week or placebo [104].…”