Article
Profound, direct and short term inhibition of effector T-cell function by dasatinib in a patient after haploidentical stem cell transplantation
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Published: | March 28, 2013 |
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Dasatinib is a dual tyrosine kinase inhibitor designed to target src kinase and the mutated bcr/abl kinase. It is widely used for the treatment of bcr/abl+ leukemias. As a known side effect, patients taking dasatinib may develop hyperleukocytosis with a predominance of CD8+ T-cells. Furthermore patients taking dasatinib are prone to severe infections indicating immunosuppressive activity of the drug.
Here we describe an 8 year old patient after haploidentical stem cell transplantation for Ph+ ALL, who was put on dasatinib medication due to increased minimal residual disease. Despite good hematologic regeneration and hyperleucocytosis he developed tri-viral disease (CMV and Adenovirus- and EBV reactivation with lymphoproliferative disease). As dasatinib was suspected to functionally impair the patient`s T-cells, we carefully analyzed T-cell activation comparing whole blood assays and assays using washed PBMC. This analysis revealed a strong serum-associated direct immune-suppressive effect, suggesting that the patient’s dasatinib medication interfered with T-cell function. T-cell function itself, as measured using washed PBMC was intact.
In consequence of this analysis, dasatinib medication was stopped and within three days the fever vanished and the patient cleared all three viruses from his blood. Whole blood analysis one week after cessation of dasatinib treatment showed full functional reactivity of the cells.
Profound functional immunosuppression from dasatinib treatment may only be detected in fresh whole blood samples and should be considered even if high CD8+ T-cell counts suggest immune competence.