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Biol Blood Marrow Transplant ; 22(5): 815-24, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26779931

RESUMEN

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.


Asunto(s)
Citotoxicidad Celular Dependiente de Anticuerpos/efectos de los fármacos , Suero Antilinfocítico/administración & dosificación , Apoptosis/efectos de los fármacos , Crisis Blástica , Enfermedad Injerto contra Huésped , Leucemia , Adulto , Anciano , Anciano de 80 o más Años , Animales , Crisis Blástica/sangre , Crisis Blástica/tratamiento farmacológico , Femenino , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Leucemia/sangre , Leucemia/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Conejos
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