In vivo effects of horse and rabbit antithymocyte globulin in patients with severe aplastic anemia
Xingmin Feng,
Phillip Scheinberg,
Angelique Biancotto,
Olga Rios,
Sarah Donaldson,
Colin Wu,
Haiyun Zheng,
Kazuya Sato,
Danielle M. Townsley,
J. Philip McCoy,
Neal S. Young
Affiliations
Xingmin Feng
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
Phillip Scheinberg
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
Angelique Biancotto
Center for Human Immunology, Autoimmunity, and Inflammation, National Institutes of Health, Bethesda, MD
Olga Rios
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
Sarah Donaldson
Washington University School of Medicine, St. Louis, MO
Colin Wu
Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
Haiyun Zheng
Department of Statistics, the George Washington University, Washington, DC
Kazuya Sato
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
Danielle M. Townsley
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
J. Philip McCoy
Center for Human Immunology, Autoimmunity, and Inflammation, National Institutes of Health, Bethesda, MD;Flow Cytometry Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
Neal S. Young
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
We recently reported that rabbit antithymocyte globulin was markedly inferior to horse antithymocyte globulin as a primary treatment for severe aplastic anemia. Here we expand on our findings in this unique cohort of patients. Rabbit antithymocyte globulin was detectable in plasma for longer periods than horse antithymocyte globulin; rabbit antithymocyte globulin in plasma retained functional capacity to bind to lymphocytes for up to 1 month, horse antithymocyte globulin for only about 2 weeks. In the first week after treatment there were much lower numbers of neutrophils in patients treated with rabbit antithymocyte globulin than in patients receiving horse antithymocyte globulin. Both antithymocyte globulins induced a “cytokine storm” in the first 2 days after administration. Compared with horse antithymocyte globulin, rabbit antithymocyte globulin was associated with higher levels of chemokine (C-C motif) ligand 4 during the first 3 weeks. Besides a much lower absolute number and a lower relative frequency of CD4+ T cells, rabbit antithymocyte globulin induced higher frequencies of CD4+CD38+, CD3+CD4−CD8− T cells, and B cells than did horse antithymocyte globulin. Serum sickness occurred around 2 weeks after infusion of both types of antithymocyte globulin. Human anti-antithymocyte globulin antibodies, especially of the IgM subtype, correlated with serum sickness, which appeared concurrently with clearance of antithymocyte globulin in blood and with the production of cytokines. In conclusion, rabbit and horse antithymocyte globulins have very different pharmacokinetics and effects on neutrophils, lymphocyte subsets, and cytokine release. These differences may be related to their efficacy in suppressing the immune system and restoring hematopoiesis in bone marrow failure. Clinicaltrials.gov identifier: NCT00260689.
