Treatment of severe aplastic anemia with antilymphocyte globulin, cyclosporine and two different granulocyte colony-stimulating factor regimens: a GITMO prospective randomized study

Abstract

Background and objectives: In a previous study we showed that patients with severe aplastic anemia (SAA) treated with anti-lymphocyte globulin (ALG), cyclosporin (CyA) and granulocyte colony-stimulating factor (G-CSF) 5 micro g/kg/day had an encouraging outcome. However, failure to respond, delayed responses, partial responses, relapses and early deaths remain significant problems. The aim of the present study was to test whether a higher dose of G-CSF (10 micro g/kg/day) would reduce these complications.

Design and methods: This was a multicenter prospective trial in 77 SAA patients treated with horse ALG (15 mg/kg/day day1-5) and CyA (5 mg/kg/day day 1-180). Patients were randomized to receive G-CSF 5 micro g/kg/day (n=38, group A) or 10 micro g/kg/day (n=39, group B) from day +1 to day +30. All patients then received G-CSF 5 micro g/kg/day from day +31 to day +90. The primary end point of this study was response at day +120. Secondary end points were early deaths, blood counts at day +120, and survival.

Results: At day +120 responses were classified as absent, partial, and complete in 12, 22, and 4 patients in group A and in 23, 7, and 9 patients in group B (p=0.001). At last follow-up these figures were respectively 9, 12, and 17 vs 19, 2, and 18 (p=0.004). Thirteen patients (5 in group A and 8 in group B) died before day 120 (p=0.3). Median peripheral blood counts on day 120 were comparable in the two groups: Hb 10.5 and 9.5 g/dL in group A and B, respectively (p=0.6), Neutrophil counts were 2.4 vs 1.9x10(9)/L in groups A and B (p=0.4) and platelet counts were, respectively, 42 vs 36x10(9)/L (p=0.3). The actuarial survival at 4 years is 72% in group A and 67% in group B (p=0.3).

Interpretation and conclusions: Increasing the dose of G-CSF does not appear to reduce early deaths, does not improve peripheral blood counts nor survival, and may reduce the response rate in patients with SAA receiving ALG and CyA.