Feasibility and eligibility of retreatment with rabbit anti-T lymphocyte globulin for aplastic anemia previously treated with horse anti-thymocyte globulin

Horse anti-thymocyte globulin (h-ATG) and rabbit anti-T lymphocyte globulin (r-ATG) are widely used for patients with acquired aplastic anemia (AA). Although these globulins have improved clinical outcomes, one-third of the cases with AA are refractory to the first course of ATG, and another third relapse after an initial successful treatment [1]. The efficacy of an additional course of h-ATG was investigated by Tichelli [2] and they reported a 63% response rate (27 out of 43 patients responded). Currently, r-ATG can be used as substitute for h-ATG for patients who have failed the first course of h-ATG. In Japan, Iki et al. [3] reported the efficacy of retreatment with h-ATG for 21 cases of AA that failed the first course of ATG as 61.9%, however, there are hardly any studies that are done on retreatment with r-ATG because the product became commercially available in April 2001 and so far the first choice ATG for AA has been h-ATG. Here, we report our clinical experience of r-ATG treatment for AA, which had previously been treated with h-ATG. During the period from January 2001 to January 2005, we performed immunosuppressive therapy with r-ATG on a total of 9 transfusion-dependent AA patients, who had failed the previous treatment with horse ATG (four relapsed after successful treatment with h-ATG, and five did not respond). The severity of disease was evaluated at the start of r-ATG therapy. Severe AA was defined as satisfying at least two of the followings: (1) absolute neutrophil count \0.5 9 10/l; (2) absolute reticulocyte count \60 9 10/l; (3) platelet count \20 9 10/l [4, 5]. All cases were given r-ATG (Zetbulin , Nippon Zoki Pharmaceutical Co., Ltd., Osaka, Japan) at a dose of 5 mg/kg per day for 5 consecutive days according to the manufacture’s instruction. Oral prednisone at 1 mg/kg per day or intravenous methylprednisone at 2 mg/kg per day were administered from day 1 to 10 for prophylaxis of serum sickness and then tapered within a few weeks. According to physicians’ decision, patients no. 1 and 2 received concomitant cyclosporine A (CsA) at the start and 3 months after the treatment and patients no. 5, 6, 7, and 8 received granulocyte colony stimulating factor (G-CSF). Hematological response was evaluated 6 months after treatment according to the definition published by Camitta [6]. The patients’ characteristics and the results of our investigation are summarized in Table 1. All patients completed a 5-day course of r-ATG without any anaphylactoid reactions or related severe adverse reactions. Although one patient had moderate serum sickness, additional corticosteroid administration resulted in prompt recovery. No severe infections (bacterial, fungal or pneumocystis pneumonia) were observed during the 6-month observation period. Four out of nine patients (44%) who were previously treated with h-ATG obtained a satisfactory response after treatment with r-ATG. The response rate of patients who had relapsed after successful h-ATG treatment was high (three out of four; 75%). On the other hand, the response rate of patients who were refractory to pre-treatment with h-ATG was poor (one out of five; 20%). These results resemble the data of Scheinberg et al. [7] that has recently been reported. In their investigation the response rate to retreatment with r-ATG/CsA for patients who had once responded h-ATG/CsA was 66% and for those who had failed to h-ATG was 30%. K. Miura (&) Y. Hatta S. Kobayashi Y. Iriyama K. Takei J. Takeuchi Department of Hematology and Rheumatology, Division of Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi Ward, Tokyo, Japan e-mail: javis@med.nihon-u.ac.jp