Efficacy of rabbit anti-thymocyte globulin in severe aplastic anemia

Abstract

BackgroundA combination of horse anti-thymocyte globulin and cyclosporine produces responses in 60-70% of patients with severe aplastic anemia. We performed a phase II study of rabbit anti-thymocyte globulin and cyclosporine as first-line therapy for severe aplastic anemia. Design and MethodsTwenty patients with severe aplastic anemia treated with rabbit anti-thymocyte globulin were compared to 67 historical control cases with matched clinical characteristics treated with horse anti-thymocyte globulin. ResultsResponse rates at 3, 6 and 12 months were similar for patients treated with rabbit anti-thymocyte globulin or horse anti-thymocyte globulin: 40% versus 55% (P=0.43), 45% versus 58% (P=0.44) and 50% versus 58% (P=0.61), respectively. No differences in early mortality rates or overall survival were observed. We then performed multivariable analyses of response at 6 months and overall survival and identified the presence of a paroxysmal nocturnal hemoglobinuria clone (P=0.01) and a pretreatment absolute reticulocyte count greater than 30¥10 9 /L (P=0.007) as independent predictors of response and younger age (P=0.003), higher pretreatment absolute neutrophil (P=0.02) and absolute lymphocyte counts (P=0.03) as independent predictors of overall survival. None of the immunogenetic polymorphisms studied was predictive of response to immunosupressive therapy. ConclusionsDespite reports suggesting differences in biological activity of different anti-thymocyte globulin preparations, rabbit and horse anti-thymocyte globulin appear to have a similar efficacy for upfront treatment of severe aplastic anemia. (Clinicaltrial.gov: NCT01231841)

Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug

“…The importance of higher reticulocyte numbers as predictors of response to IST have been noted previously, perhaps reflecting residual HSC numbers. 29,30 Why endogenous pathways do not stimulate normalization of the HSPC compartment, if immune attack has abated, particularly given the very high endogenous circulating levels of TPO in patients with SAA, is unclear. 31,32 It is likely that a critical mass of HSPCs is required for bone marrow recovery in patients, although HSPC numbers remain low even in those who normalize blood counts.…”

Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood

“…35,36 However, several recent studies on aplastic anemia showed an inferior response and/or decreased survival after rabbit-ATG compared with those after horse-ATG, [16][17][18][19] whereas other studies described comparable results. [20][21][22] Notably, none of the reports indicated a superior efficacy of rabbit-ATG over horse-ATG. The majority of previous reports in adults with MDS have involved horse-ATG, and there are limited data on the efficacy of rabbit-ATG.…”

“…[17][18][19] No published series of patients with aplastic anemia has shown that rabbit-ATG is superior to horse-ATG in the context of first-line IST. [16][17][18][19][20][21][22] To date, there have only been a few reports on the efficacy of IST with rabbit-ATG in patients with MDS. 10,23,24 In this study, we compared the outcome of IST using horse-ATG with that of IST using rabbit-ATG in a large series of children with RCC.…”

Idiopathic severe aplastic anemia with a delayed response to immunosuppressive therapy: a case report

“…It can produce more profound and prolonged lymphocytopenia 15. In addition, rATG may selectively promote the expansion of regulatory T cells and induce in vivo immune tolerance through this mechanism.…”

“…Manuel G. concluded that despite reports suggesting differences in biological activity of different ATG preparations, rabbit and horse ATG appear to have a similar efficacy for up‐front treatment of severe aplastic anemia 15. Similarly, Shin et al pointed out that the efficacy of both the rATG with CSA and hATG is the same.…”