Long-term outcome of a randomized controlled study in patients with newly diagnosed severe aplastic anemia treated with antithymocyte globulin and cyclosporine, with or without granulocyte colony-stimulating factor: a Severe Aplastic Anemia Working Party Trial from the European Group of Blood and Marrow Transplantation

Abstract

This follow-up study of a randomized, prospective trial included 192 patients with newly diagnosed severe aplastic anemia receiving antithymoglobulin and cyclosporine, with or without granulocyte colony-stimulating factor (G-CSF). We aimed to evaluate the long-term effect of G-CSF on overall survival, event-free survival, probability of secondary myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), clinical paroxysmal nocturnal hemoglobinuria, relapse, avascular osteonecrosis and chronic kidney disease. The median follow-up was 11.7 years (95% CI, 10.9-12.5). The overall survival rate at 15 years was 57±12% in the group given G-CSF and 63±12% in the group not given G-CSF (P=0.92); the corresponding event-free survival rates were 24±10% and 23±10%, respectively (P=0.36). In total, 9 patients developed MDS or AML, 10 only a clonal cytogenetic abnormality, 7 a solid cancer, 18 clinical paroxysmal nocturnal hemoglobinuria, 8 osteonecrosis, and 12 chronic kidney disease, without any difference between patients treated with or without G-CSF. The cumulative incidence of MDS, AML or isolated cytogenetic abnormality at 15 years was 8.5±3% for the G-CSF group and 8.2±3% for the non-G-CSF group (P=0.90). The cumulative incidence of any late event including myelodysplastic syndrome or acute myeloid leukemia, isolated cytogenetic abnormalities, solid cancer, clinical paroxysmal nocturnal hemoglobinuria, aseptic osteonecrosis, chronic kidney disease and relapse was 50±12% for the G-CSF group and 49±12% for the non-G-CSF group (P=0.65). Our results demonstrate that it is unlikely that G-CSF has an impact on the outcome of severe aplastic anemia; nevertheless, very late events are common and eventually affect the prognosis of these patients, irrespectively of their age at the time of immunosuppressive therapy (NCT01163942).

Copyright© 2020 Ferrata Storti Foundation.

Figures

Figure 1

Outcomes of patients with severe aplastic anemia treated with horse antithymocyte globulin and cyclosporine with or without granulocyte colony-stimulating factor. (A, B) Overall survival (A) and event-free survival (B) of patients with severe aplastic anemia treated with horse antithymocyte globulin and cyclosporine with or without granulocyte colony-stimulating factor. Events included relapse, non-response at day 120, subsequent stem cell transplantation, myelodysplastic syndrome/acute myeloid leukemia, solid cancer, paroxysmal nocturnal hemoglobinuria or death. G-CSF: granulocyte colony-stimulating factor.

Figure 2

Overall survival and event-free survival according to age groups. (A, B) Overall survival (A) and event-free survival (B) of patients with severe aplastic anemia treated with horse antithymocyte globulin and cyclosporine with or without granulocyte colony-stimulating factor according to age groups at time of randomization: patients

Figure 3

Cumulative incidence of late complications of patients with severe aplastic anemia treated with horse antithymocyte globulin and cyclosporine with or without granulocyte colony-stimulating factor. (A) Cumulative incidence of relapse of patients with severe aplastic anemia (SAA) treated with horse antithymocyte globulin (ATG) and cyclosporine (CSA) with or without granulocyte colony-stimulating factor (G-CSF). (B) Cumulative probability of being transplanted (death without transplant is the competing event) of patients with SAA treated in first-line with horse ATG and CSA with or without G-CSF. (C) Cumulative incidence of clonal evolution to a hematologic malignancy (myelodysplastic syndrome/acute myeloid leukemia or isolated cytogenetic abnormality) of patients with SAA treated with horse ATG and CSA with or without G-CSF. (D) Cumulative incidence of any late event (relapse, myelodysplastic syndrome/acute myeloid leukemia, isolated cytogenetic abnormality, solid cancer, clinical paroxysmal nocturnal hemoglobinuria, aseptic osteonecrosis, chronic kidney disease) of patients with SAA treated with horse ATG and CSA with or without G-CSF.