Treatment of severe aplastic anemia with antithymocyte globulin and cyclosporin A with or without G-CSF in adults: a multicenter randomized study in Japan

Abstract

We report the results of a randomized study to elucidate whether addition of granulocyte colony-stimulating factor (G-CSF) to immunosuppressive therapy is valuable for the treatment of severe aplastic anemia (SAA) in adults. A total of 101 previously untreated patients (median age, 54 years; range, 19 to 75 years) were randomized to receive antithymocyte globulin (ATG) and cyclosporin A (CyA) (G-CSF؊ group) or ATG, CyA, and G-CSF (G-CSF؉ group). In the G-CSF؉ group, the hematologic response rate at 6 months was higher (77% vs 57%; P ‫؍‬ .03) than in the G-CSF؊ group. No differences were observed between the groups in terms of the incidence of infections and febrile episodes. There were no differences between the G-CSF؊ group and the G-CSF؉ group in terms of survival (88% vs 94% at 4 years), and the development of myelodysplastic syndrome (MDS)/acute leukemia (AL) (1 patient vs 2 patients). However, the relapse rate was lower in the G-CSF؉ group compared with the G-CSF؊ group (42% vs 15% at 4 years; P ‫؍‬ .01). Further follow-up is required to elucidate the role of G-CSF in immunosuppressive therapy for adult SAA. (Blood.

Supportive care in severe and very severe aplastic anemia

“…4,34 One study from Japan comparing immunosuppression with or without G-CSF reported a lower relapse rate in the G-CSF group. 5 This was not confirmed in a large European multi-center trial. 4 One must also take into account the potential risk that G-CSF increases the incidence of secondary clonal disorders.…”

“…The individual risk of a patient is mainly determined by the neutrophil, and monocyte counts. [2][3][4][5][6][7][8] During the past two decades, infection-related mortality and invasive fungal infections decreased. 2 However, infections are still the major threat for patients with severe or very severe AA.…”

“…In the most recently published large clinical trials in AA, the most prevalent complications and the major causes of death still were bacterial and fungal infections. [3][4][5] In the following sections, we will summarize recommendations on the major aspects of supportive treatment in AA, that is, prophylaxis and early treatment of infections, transfusion strategy and treatment of iron overload. …”

Hematopoietic growth factors in aplastic anemia patients treated with immunosuppressive therapy-systematic review and meta-analysis

“…All six trials reported overall mortality, five of them at 100 days, 4,16,17,32,34 (Figure 2). Sensitivity analysis for mortality rate at 100 days showed a higher RR (favoring control) with adequate allocation concealment and generation, RR 1.57 (95% CI 0.44-5.55, 3 trials) compared to unclear methods, RR 1.15 (95% CI 0.34-3.84, 2 trials), without a statistically significant result or difference between the subgroups.…”

“…Duplicate publication -1 trial 31 RCTs included in the meta-analysis (n =6) 4,16,17,[32][33][34] © F e r r a t a S t o r t i case analysis were extracted. For the main analysis, all trials were pooled.…”