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 Horse ATG has been replaced by rabbit ATG in many countries due to the unavailability of the former product.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 = .009) and 0% versus 34.0% (P = .04), respectively. On day +100, the probability of proven/probable invasive fungal disease (IFD) was higher in patients conditioned with rabbit ATG, 31.2% versus 5.5%, respectively (P = .04). Earlier cytomegalovirus (CMV) reactivation (40 versus 50 days; P = .02) was observed with rabbit ATG. An inferior lymphocyte count on days +30 (0.360 versus 0.814 × 10(9)/L; P = .01) and +90 (0.744 versus 1.330 × 10(9)/L; P = .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 = .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.