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.
Highlights
Severe aplastic anemia (SAA) is a rare disorder leading to bone marrow failure which, if left untreated, is invariably fatal
Recent data have shown that rabbit antithymocyte globulin (ATG) depletes different lymphocyte subsets compared to horse ATG, and rabbit ATG is more likely to promote the expansion of CD4 + CD25 bright FOXP3+ regulatory T cells [2, 20]. These data establish rabbit and horse ATG as having distinct in vitro and in vivo immunosuppressive properties that should be considered when selecting the formulation of ATG to be utilized in the transplant conditioning regimen. In this paired case report, we demonstrate the unique experience of two monozygotic patients with bone marrow failure and myelodysplastic syndrome (MDS) who received an allogeneic HPSC transplant from the same donor, with the only difference in the transplant regimen being the formulation of ATG used in the preparative regimen
Rabbit ATG resulted in superior graftversus-host disease (GVHD) prophylaxis in twin #1, which came at the cost of impeding donor T cell engraftment placing the patient at risk for graft rejection
Summary
Severe aplastic anemia (SAA) is a rare disorder leading to bone marrow failure which, if left untreated, is invariably fatal. Equine or horse ATG (Atgam) and rabbit ATG (thymoglobulin) are two antithymocyte globulin preparations that are available in the United States of America, for clinical use as immunosuppressive agents Both drugs have been used in off-label applications as conditioning agents for allogeneic HSCT for a variety of disorders including SAA. Case report Twin #1 and twin #2 are two Vietnamese female monozygotic twins who were born prematurely at 8 months of gestation with a birth weight of approximately 1.8 kg each They were both diagnosed with SAA at 2 years of age when they presented with symptoms related to pancytopenia. Peripheral blood counts demonstrated an absolute neutrophil count (ANC) of 417 cells/μl, a platelet count of 16 k/μl, hemoglobin of 10 g/dl, and an absolute reticulocyte count of 61 k/μl She failed a trial of danazol therapy and in April 2002, commenced treatment with horse ATG 40 mg/kg/day for 4 days combined with CSA. A repeat bone marrow biopsy performed in 2004 revealed 5–15 %
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