Different Outcomes between Cyclophosphamide Plus Horse or Rabbit Antithymocyte Globulin for HLA-Identical Sibling Bone Marrow Transplant in Severe Aplastic Anemia

Abstract

The standard regimen for HLA-identical sibling bone marrow transplant (BMT) in severe aplastic anemia (SAA) is cyclophosphamide (Cy) and horse antithymocyte globulin (ATG). Horse ATG has been replaced by rabbit ATG in many countries due to the unavailability of the former product. This study was designed to assess if these ATG preparations are interchangeable in the preparative regimen for matched related BMT in SAA. Forty consecutive BMTs were retrospectively analyzed: 20 received Cy plus horse ATG and 20 received Cy plus rabbit ATG as the preparative regimen. Conditioning with rabbit ATG was protective against acute graft-versus-host disease (aGVHD) grades II-IV and moderate-severe chronic GVHD (cGVHD), with incidence rates of 0% versus 35.2% (P 5 .009) and 0% versus 34.0% (P 5 .04), respectively. On day 1100, the probability of proven/probable invasive fungal disease (IFD) was higher in patients conditioned with rabbit ATG, 31.2% versus 5.5%, respectively (P 5 .04). Earlier cytomegalovirus (CMV) reactivation (40 versus 50 days; P 5.02) was observed with rabbit ATG. An inferior lymphocyte count on days 130 (0.360 versus 0.814 Â 10 9 /L; P 5 .01) and 190 (0.744 versus 1.330 Â 10 9 /L; P 5 .006) was noticed in recipients of rabbit ATG. The incidence of stable mixed chimerism was higher in recipients of rabbit ATG (18.2% versus 80%, respectively; P 5 .004). These results suggest that horse and rabbit ATG preparations have different biological and clinical properties and should not be used interchangeably in the preparative regimen for related BMT in SAA.

Anti-thymocyte globulin as graft- versus -host disease prevention in the setting of allogeneic peripheral blood stem cell transplantation: a review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…23,24 Furthermore, a retrospective study from the Brazilian National Cancer Institute in a cohort of 40 patients with aplastic anemia receiving BMT from HLA-identical siblings observed higher incidences of grade II-IV acute GvHD (35% versus 0%, P=0.009) and moderate/severe chronic GvHD (3-year rate: 34% versus 0%, P=0.04) in the 20 patients conditioned with cyclophosphamide plus ATG-h (90 mg/kg total dose) than in those conditioned with cyclophosphamide plus ATG-T (8 mg/kg total dose). 25 These findings might be due to the fact that, in comparison to rabbit ATG, ATG-h induces less profound and less durable lymphopenia, even if it is administered at higher doses. 25,26 Antigens targeted by ATG-T have been well described and include antigens expressed on T cells (such as CD2, CD3, CD4, CD7, or CD8), B cells, natural killer cells, macrophages and dendritic cells, as well as HLA class 1 and HLA-DR. 27 Recognition by ATG-T of B cells and dendritic-cell antigens can also be attributed to the presence of antigen-presenting cells, thymic stromal cells and B cells in thymus fractions, although they are composed mainly of T cells.…”

“…25 These findings might be due to the fact that, in comparison to rabbit ATG, ATG-h induces less profound and less durable lymphopenia, even if it is administered at higher doses. 25,26 Antigens targeted by ATG-T have been well described and include antigens expressed on T cells (such as CD2, CD3, CD4, CD7, or CD8), B cells, natural killer cells, macrophages and dendritic cells, as well as HLA class 1 and HLA-DR. 27 Recognition by ATG-T of B cells and dendritic-cell antigens can also be attributed to the presence of antigen-presenting cells, thymic stromal cells and B cells in thymus fractions, although they are composed mainly of T cells. 27 Furthermore, ATG-T also contains antibodies targeting antigens involved in cell adhesion and cell trafficking, as well as antigens involved in inflammation, apoptosis and cell proliferation.…”

TCR-alpha/beta and CD19 depletion and treosulfan-based conditioning regimen in unrelated and haploidentical transplantation in children with acute myeloid leukemia

“…14 In particular, horse antithymocyte globulin, which was used in our trial, is less immunosuppressive than rabbit anti-thymocyte globulin, which was used in other trials. 19 Another detail that potentially contributed to the better GvHD control in the reports from the Rome group is that rituximab was included in the preparative regimen.…”

Marrow grafts from HLA-identical siblings for severe aplastic anemia: does limiting the number of transplanted marrow cells reduce the risk of chronic GvHD?

“…20 Atta et al described chronic GVHD incidences of 34% and 0%, respectively, comparing horse ATG to rabbit ATG in the conditioning regimen; the shortest follow-up was 8 days. 21 Of note, even though no chronic GVHD was seen with rabbit ATG, survival among patients given horse ATG was comparable, 65% versus 63%, respectively. Moreover, more than half of the patients were still at risk for developing chronic GVHD.…”