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

Abstract

Refractory cytopenia of childhood is the most common subtype of myelodysplastic syndrome in children. In this study, we compared the outcome of immunosuppressive therapy using horse antithymocyte globulin (n=46) with that using rabbit antithymocyte globulin (n=49) in 95 patients with refractory cytopenia of childhood and hypocellular bone marrow. The response rate at 6 months was 74% for horse antithymocyte globulin and 53% for rabbit antithymocyte globulin (P=0.04). The inferior response in the rabbit antithymocyte globulin group resulted in lower 4-year transplantation-free (69% versus 46%; P=0.003) and failure-free (58% versus 48%; P=0.04) survival rates in this group compared with those in the horse antithymocyte globulin group. However, because of successful second-line hematopoietic stem cell transplantation, overall survival was comparable between groups (91% versus 85%; P=ns). The cumulative incidence of relapse (15% versus 9%; P=ns) and clonal evolution (12% versus 4%; P=ns) at 4 years was comparable between groups. Our results suggest that the outcome of immunosuppressive therapy with rabbit antithymocyte globulin is inferior to that of horse antithymocyte globulin. Although immunosuppressive therapy is an effective therapy in selected patients with refractory cytopenia of childhood, the long-term risk of relapse or clonal evolution remains. (ClinicalTrial.gov identifiers: NCT00662090).

Figures

Figure 1.

Overview of the 450 patients with refractory cytopenia of childhood. The patients were subdivided according to karyotype and bone marrow cellularity. Of the 332 patients with a normal karyotype, one or two cytogenetic aberrations (excluding 7/7q-), or no result of metaphase cytogenetics and a hypocellular bone marrow, two exhibited progression to refractory anemia with excess blasts before hematopoietic stem cell transplantation (HSCT), 131 received neither immunosuppressive therapy (IST) nor HSCT within 180 days after diagnosis (watch and wait strategy), 115 received IST, and 84 received HSCT from a matched sibling donor (MSD; n = 39), an unrelated donor (UD; n = 44), or a mismatched family donor (MMFD; n = 1) as primary therapy. ND: no data available.

Figure 2.

Overall (A–B), transplantation-free (C), and failure-free (D) survival rates after immunosuppressive therapy (IST) in children with refractory cytopenia of childhood treated with either horse antithymocyte globulin (horse-ATG) or rabbit-ATG. To estimate failure-free survival, death, clonal evolution, a second course of IST, requirement of hematopoietic stem cell transplantation, and relapse were considered to indicate treatment failure (D).