Conditioning with rabbit versus horse ATG dramatically alters clinical outcomes in identical twins with severe aplastic anemia transplanted with the same allogeneic donor

Abstract

Severe aplastic anemia (SAA) is a rare disorder leading to bone marrow failure, which if left untreated, is invariably fatal. Conventional therapies with immunosuppressive therapy or allogeneic hematopoietic stem cell transplantation (HSCT) are highly effective. HSCT can offer a greater outcome in younger patients who have an available HLA match-related donor. Recent studies showing the addition of antithymocyte globulin (ATG) to the conditioning regimen improves engraftment and reduces the risk of graft-versus-host disease (GVHD).There are currently two ATG preparations in the USA, equine (or horse) and rabbit ATG. These agents are pharmacologically distinct, having significant differences in their pharmacokinetics and in vivo immunosuppressive effects [N Engl J Med 365(5):430–438, 2011]. Here, we report a case of two monozygotic twins with constitutional SAA that evolved to myelodysplastic syndrome (MDS) who both underwent allogeneic peripheral blood stem cell transplantation (PBSC) from the same single HLA antigen mismatched sibling donor with the only difference in the transplant regimen being the type of ATG used in the preparative regimen; one twin received horse ATG and the other received rabbit ATG during conditioning. This report emphasizes that dramatic differences in donor T cell chimerism and clinical outcomes including GVHD can occur as a consequence of the type of ATG that is utilized in the transplant conditioning regimen. These differences highlight that these agents should not be considered interchangeable drugs when used in this setting.

Upfront haploidentical transplant for acquired severe aplastic anemia: registry-based comparison with matched related transplant

“…Our findings showed that the HID cohort without in vitro T cell depletion had myeloid (97.75 vs. 97.10%) and platelet (96.63 vs. 95.65%) engraftment rates comparable to those of the MRD cohort. As analyzed in our previous research [21], the reasons for these encouraging engraftment outcomes in mismatched transplants may be multifactorial, including adding BU to CY + ATG for intensified conditioning [36, 37], using G-CSF-mobilized grafts [38] and combining CsA, MTX, and MMF as GVHD prophylaxis.…”

Clinical outcomes in adult patients with aplastic anemia: A single institution experience

“…9,14,15 The dissimilar nature of the two ATG preparations is further highlighted by the dramatic differences they have on donor T cell engraftment, and the risk of acute and chronic GVHD when utilized in the transplant conditioning regimen under identical settings. 16 …”

Anti‐thymocyte globulin improves survival free from relapse and graft‐versus‐host disease after allogeneic peripheral blood stem cell transplantation in patients with Philadelphia‐negative acute lymphoblastic leukemia: An analysis by the Acute Leukemia Working Party of theEBMT

“…Rabbit ATG, in comparison with the horse formulation, is in turn associated with more effective lymphocyte depletion and enhancement of the number and function of regulatory T cells . The beneficial effect of the addition of a rabbit formulation instead of the horse formulation of ATG to the conditioning regimen before allogeneic bone marrow transplantation for severe aplastic anemia on clinical outcomes, including GVHD, was recently demonstrated . All the aforementioned differences may influence both immunosuppressive and potential antileukemic properties of the drug and indicate that the 3 available ATG formulations should not be considered interchangeable agents.…”