First line treatment of aplastic anemia with thymoglobuline in Europe and Asia: Outcome of 955 patients treated 2001‐2012

Abstract

The aim of this study was to assess the outcome of patients with aplastic anemia (AA), receiving rabbit anti-thymocyte globulin (Thymoglobulin, SANOFI) and cyclosporin, as first line treatment. Eligible were 955 patients with AA, treated first line with Thymoglobulin, between 2001 and 2008 (n = 492), or between 2009 and 2012 (n = 463). The median age of the patients was 21 years (range 1-84). Mortality within 90 days was 5.7% and 2.4%, respectively in the two time periods (P = .007).The actuarial 10-year survival for the entire population was 70%; transplant free survival was 64%. Predictors of survival in multivariate analysis, were severity of the disease, patients age and the interval between diagnosis and treatment. Survival was 87% vs 61% for responders at 6 months versus nonresponders (P < .0001). The 10-year survival of nonresponders at 6 months, undergoing a subsequent transplant (n = 110), was 64%, vs 60% for patient not transplantated (n = 266) (P = .1). The cumulative incidence of response was 37%, 52%, 65% respectively, at 90, 180, and 365 days. In multivariate analysis, negative predictors of response at 6 months, were older age, longer interval diagnosis treatment, and greater severity of the disease. In conclusion, early mortality is low after first line treatment of AA with Thymoglobulin, and has been further reduced after year 2008. Patients age, together with interval diagnosis-treament and severity of the disease, remain strong predictors of response and survival.

Multivariate logistic analysis of predictors of response to immunosuppressive therapy in children with aplastic anemia: a double-center study

“…Several factors have been proposed to predict the responsiveness to IST in adult patients with AA, include younger age [12,13], a higher absolute neutrophil count (ANC) [14], a higher absolute reticulocyte count (ARC), a higher actual lymphocyte count (ALC) [15], a higher baseline platelet count [16], a shorter interval between diagnosis and IST [13,17], and higher CSA levels during the 1st-2nd week of IST [18]. However, less data are available from pediatric patients with AA in terms of their responsiveness and risk factors to IST.…”

Prospective randomized trial comparing two doses of rabbit anti‐thymocyte globulin in patients with severe aplastic anaemia

“…The patients were divided into 4 groups; 1·0−2·5 mg/kg/day ( n = 56), 2·6−3·0 mg/kg/day ( n = 29), 3·1−3·5 mg/kg/day ( n = 46), and 3·6−5·0 mg/kg/day ( n = 38). Their results showed that ATG doses did not correlate with response rates at 6 months: 29%, 28%, 35%, and 34%, respectively ( P = 0·85) (Cle et al , ) Bacigalupo et al (). analysed response rates to rabbit ATG in 955 patients with AA from European and Asian countries and found a 52% haematological response rate at 6 months.…”

“…On the other hand, a retrospective study involving Asian cohorts showed equivalent response rates at 6 months between the rabbit ATG group ( n = 158) and horse ATG group ( n = 292) (55% vs. 60%, P = 1·000) (Jeong et al , ). Another retrospective study recently conducted in Europe and Asia revealed a 52% response rate to rabbit ATG treatment at 6 months among the 955 patients enrolled (Bacigalupo et al , ). Accordingly, the response rates reported in the aforementioned large retrospective studies were comparable to those presented in the current prospective study.…”

“…These differences in response rates may perhaps reflect variations in the rabbit ATG dose used among each research centre, considering that the studies from the NIH and EBMT groups used a rabbit ATG dose of 3·5 and 3·75 mg/kg/day for 5 days (Scheinberg et al , ; Marsh et al , ), which was higher than that used in the studies from Asian countries (Jeong et al , ; Bacigalupo et al , ).…”

“…Patients were stratified into three groups according to ATG dose, ≤2·5 ( n = 253), 2·5−3·5 ( n = 278) and ≥3·75 mg/kg/day ( n = 424), in which the response rates were 56%, 60% and 67% in children, and 58%, 42% and 69% in adults ( P < 0·001), respectively. The best responses were seen in both children and adults receiving a dose of ≥3·75 mg/kg/day (Bacigalupo et al , ). Although the reasons for the discrepant results remains unknown, a considerable difference in the ORRs had been found between both studies, suggesting that ethnic factors might have been responsible for the difference in response rates.…”