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Dasatinib medication causing profound immunosuppression in a patient after haploidentical SCT: functional assays from whole blood as diagnostic clues

Bone Marrow Transplantation volume 48, pages 875–877 (2013)Cite this article

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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.1, 2 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.3 In vitro, as well as in murine studies, dasatinib has been shown to suppress effector memory T-cell function by blocking TCR-triggering via inhibition of the src-kinase Lck.4, 5, 6, 7, 8, 9 Here, we describe a patient after haploidentical SCT for Ph+ ALL, who experienced severe immunosuppression due to dasatinib treatment. Analysis of the patient’s serum samples at different time points, as well as comparison of functional immune assays for T-cell activation either in whole blood or in washed PBMC provides evidence for a direct suppressive effect of dasatinib in the serum of this patient.

To prove this hypothesis, we performed intracellular cytokine staining on PBMC from healthy donors incubating the cells either with 50% patient serum or control serum. T-cell responses were almost completely suppressed when patient serum was present during the incubation phase (Figure 2b).

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  1. Pediatric Hematology, Oncology and Stem Cell Transplantation, Children's Hospital, University of Würzburg, Würzburg, Germany

    M Wölfl, F Langhammer, V Wiegering, M Eyrich & P G Schlegel

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  1. M Wölfl
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  2. F Langhammer
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  3. V Wiegering
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Correspondence to M Wölfl.

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Wölfl, M., Langhammer, F., Wiegering, V. et al. Dasatinib medication causing profound immunosuppression in a patient after haploidentical SCT: functional assays from whole blood as diagnostic clues. Bone Marrow Transplant 48, 875–877 (2013). https://doi.org/10.1038/bmt.2012.246

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