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) Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood 16 In addition, a number of non-randomized studies showed inferior results for rabbit-ATG in adults and children with aplastic anemia. [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. Methods Selection of patients for immunosuppressive therapyBone marrow and peripheral blood smears and bone marrow biopsies were centrally reviewed by reference pathologists in each country and the diagnosis of RCC was made according to the WHO criteria. 1,25 Fanconi anemia was excluded in all patients. Patients with RCC aged ≤18 years were enrolled in the prospective studies EWOG-MDS-98 (05/1998-12/2006) and EWOG-MDS-2006 (01/2007-08/2011. These studies were approved by the institutional review board of each participating institution. Written informed consent was provided by the patients' parents according to the Declaration of Helsinki.Patients with RCC are treated according to a risk-based strategy (Figure 1). Because of a high risk of disease progression, all patients with monosomy 7/7q-or three or more chromosomal aberrations undergo allogeneic hematopoietic stem cell transplantation (HSCT). 26 For patients without these unfavorable karyot...

Immune suppression for childhood acquired aplastic anemia and myelodysplastic syndrome: where next?

“…In a similar study published in this issue of the Journal, Yoshimi et al 12 prospectively evaluated responses following IST with horse ATG (Lymphoglobulin) until 2007 and rabbit ATG (Thymoglobulin) after 2007 in a selected cohort of children with RCC. All children enrolled in this study were carefully selected to maximize response to IST and minimize disease progression.…”

“…12 While IST can, undoubtedly, always be started earlier than an upfront matched unrelated donor transplant, the time to cellular recovery is slow following IST (typically 3-6 months). In contrast, cellular recovery following matched unrelated donor transplantation is much quicker (normally a month).…”

Loss of B cells and their precursors is the most constant feature of GATA-2 deficiency in childhood myelodysplastic syndrome

“…31,32 Differences between the overlapping categories RCC and AA are a frequent subject of discussion, especially in patients with hypocellular BM and without adverse cytogenetics. The separation of patients into two categories seems to be less relevant because immunosuppressive therapy is indicated for both disease groups, [33][34][35] and there is no difference in prognosis nor in the probability of progression into advanced MDS. 35 We observed significant differences between RCC and AA in a limited number of parameters in BM (decreased in AA: CD34 pos , CD117 pos , granulocytes and erythroid precursors, increased in AA: CD19 pos and lymphocytes).…”

The current perspective of low-grade myelodysplastic syndrome in children

“…IST consisting of antithymocyte globulin (ATG) and cyclosporine has proven to be effective in a subset of children with low-grade MDS, with response rate ranging from 30 to 70 % [5,6,14,15,21]. Some patients with chromosomal abnormalities or multilineage dysplasia were also reported to respond to IST [5,6,14,15,21].…”

“…Some patients with chromosomal abnormalities or multilineage dysplasia were also reported to respond to IST [5,6,14,15,21]. However, patients who received IST remain at risk of clonal evolution and relapse, and the long-term failure-free survival rate was estimated as only 40-50 % [5,21]. As reliable biomarkers that can predict response have not yet identified, candidates for IST should be selected with utmost caution.…”