Treatment of aplastic anaemia (AA) with antilymphocyte globulin (ALG) and methylprednisolone (MPred) with or without androgens: a randomized trial from the EBMT SAA working party

Abstract

134 patients with acquired aplastic anaemia (AA) were given HALG 15 mg/kg/d for 5 d and methylprednisolone for 1 month, and randomized to receive (n = 69) or not (n = 65) oxymetholone 2 mg/kg/d p.o. daily for 4 months. Early mortality (< 120 d) was comparable in the two arms 12/69 (17%) and 11/65 (17%), and correlated with the severity of the disease (39%, 10% and 6% respectively in patients with neutrophil counts (PMN) < 0.2, 0.2-0.5, > 0.5 x 10(9)/l). The response rate at 120 d was significantly greater in patients receiving androgens (56% v 40%; P = 0.04); it was 68% v 48% (P = 0.02) in patients surviving 120 d, and 78% v 27% (P = 0.03) in females with PMN less than 0.5 x 10(9)/l. In a multivariate Cox analysis on patients with less than 0.5 x 10(9)/l PMN, the probability of responding without androgens was reduced compared to the androgen treatment arm (P = 0.05). Survival was comparable in the two groups (71% v 65%). It was superior (74% v 50%), but not significantly (P = 0.1) in females with PMN < or = 0.5 x 10(9)/l receiving androgens. Side-effects, including biochemical abnormalities and virilization, could be controlled and were reversible. In conclusion, the addition of androgens to HALG and methylprednisolone as first line treatment of aplastic anaemia significantly improves the response rate at 4 months, particularly in females with low neutrophil counts, although there is no significant effect on short-term survival. The reversible side-effects warrant the use of androgens as an adjunct to the first course of ALG in females with severe AA.

How I treat acquired aplastic anemia

“…74 However, in a second randomized trial, women receiving ATG1androgens had significantly superior response rates, although comparable survival, as with ATG without androgens. 75 Intensified IST with ATG and androgens produced a 77% response rate and 78% survival at 5 years in a single-center study. 76 We have shown a 59% response rate with testosterone 40 mg /day (5 days/week) in patients with persistent cytopenia after IST.…”

Relapse of aplastic anemia in children after immunosuppressive therapy: a report from the Japan Childhood Aplastic Anemia Study Group

“…5 The severity of disease was determined according to currently used criteria. 13,14 Disease was considered severe if at least two of the following were present: (i) neutrophil count less than 0.5×10 /L with a hypocellular bone marrow. Allogeneic bone marrow transplantation was recommended for those patients with severe or very severe disease who had a matched sibling donor.…”

Antithymocyte globulin with or without cyclosporin A: 11-year follow-up of a randomized trial comparing treatments of aplastic anemia

“…Published information relies on retrospective or registry data 6,8,9 or follow-up is short. 7,[10][11][12][13] Here we report 11-year results of the randomized German trial 7 that demonstrate the potential and the problems associated with the IST approach to aplastic anemia.…”