Antithymocyte Globulin at Clinically Relevant Concentrations Kills Leukemic Blasts
| Autor: | Poonam Dharmani-Khan, Loree Larratt, Rosy Dabas, Caylib Durand, Don Morris, Rachelle Lee, Maria Theresa Servito, Monica Modi, Faisal Khan, Tiffany Van Slyke, Joseph Brandwein, Andrew Daly, Joanne Luider, Jan Storek |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male endocrine system Globulin Graft vs Host Disease Apoptosis 03 medical and health sciences 0302 clinical medicine Medicine Animals Humans Cytotoxicity Aged Antilymphocyte Serum Aged 80 and over Transplantation Acute leukemia Leukemia biology business.industry Antibody-Dependent Cell Cytotoxicity Hematology Middle Aged medicine.disease Graft-versus-host disease 030220 oncology & carcinogenesis Immunology biology.protein Methotrexate Female Rabbits business Blast Crisis 030215 immunology medicine.drug |
| Zdroj: | Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 22(5) |
| ISSN: | 1523-6536 |
| Popis: | In contrast to cyclosporine or methotrexate, rabbit antithymocyte globulin (ATG) used for graft-versus-host disease (GVHD) prophylaxis with myeloablative conditioning does not increase the risk of relapse after hematopoietic cell transplantation. The reason for this is unknown. We hypothesized that ATG at concentrations achieved with our standard ATG dose of 4.5 mg/kg exerts antileukemic activity. We measured ATG-induced killing of leukemic blasts via complement-dependent cytotoxicity (CDC) and via complement-independent cytotoxicity (CIC) in marrow or blood from 36 patients with newly diagnosed acute leukemia. The median percentage of blasts killed by CDC was 0.3% at 1 mg/L ATG, 2.8% at 10 mg/L ATG, 12.6% at 25 mg/L ATG, and 42.2% at 50 mg/L ATG. The median percentage of blasts killed by CIC after a 4-hour incubation with ATG was 1.9% at 1 mg/L ATG, 7.15% at 10 mg/L ATG, 12.1% at 25 mg/L ATG, and 13.9% at 50 mg/L ATG. CIC appeared to represent a direct induction of apoptosis by ATG. There was a high variability in the sensitivity of the blasts to ATG; at 50 mg/L, the percentage of blasts killed ranged from 2.6% to 97.2% via CDC and from 1.4% to 69.9% via CIC. In conclusion, ATG at clinically relevant concentrations kills leukemic blasts in vitro. Some acute leukemias are highly sensitive to ATG, whereas others are relatively resistant. This finding could lead to personalized administration of ATG. |
| Databáze: | OpenAIRE |
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