gms | German Medical Science

21. Jahrestagung der Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI)

Deutsche Gesellschaft für Pädiatrische Infektiologie (DGPI)

25.04. - 27.04.2013, Würzburg

Profound, direct and short term inhibition of effector T-cell function by dasatinib in a patient after haploidentical stem cell transplantation

Meeting Abstract

  • corresponding author presenting/speaker M. Wölfl - Universitätskinderklinik, Pädiatrische Stammzelltransplantation - Würzburg, Deutschland
  • F. Langhammer - Universitätskinderklinik, Pädiatrische Stammzelltransplantation - Würzburg, Deutschland
  • V. Wiegering - Universitätskinderklinik, Pädiatrische Stammzelltransplantation - Würzburg, Deutschland
  • M. Eyrich - Universitätskinderklinik, Pädiatrische Stammzelltransplantation - Würzburg, Deutschland
  • P. G. Schlegel - Universitätskinderklinik, Pädiatrische Stammzelltransplantation - Würzburg, Deutschland

Deutsche Gesellschaft für Pädiatrische Infektiologie. 21. Jahrestagung der Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI). Würzburg, 25.-27.04.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. Doc13dgpi48

doi: 10.3205/13dgpi48, urn:nbn:de:0183-13dgpi486

Published: March 28, 2013

© 2013 Wölfl et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

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.