Immunological monitoring of newly diagnosed CML patients treated with bosutinib or imatinib first-line

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Changes in the immune system induced by tyrosine kinase inhibitors (TKI) have been shown to positively correlate with therapy responses in chronic myeloid leukemia (CML). However, only a few longitudinal studies exist and no randomized comparisons between two TKIs have been reported. Therefore, we prospectively analyzed the immune system of newly diagnosed CML patients treated with imatinib (n = 20) or bosutinib (n = 13), that participated in the randomized BFORE trial (NCT02130557). Comprehensive immunophenotyping, plasma protein profiling, and functional assays to determine activation levels of T and NK cells were performed at diagnosis, 3, and 12 months after therapy start. All results were correlated with clinical parameters such as Sokal risk and BCR-ABL load measured according to IS%. At diagnosis, low Sokal risk CML patients had a higher frequency of cytotoxic cells (CD8 + T and NK cells), increased cytotoxic potential of NK cells and lower frequency of naïve and central memory CD4 + T cells. Further, soluble plasma protein profile divided patients into two distinct clusters with different disease burden at diagnosis. During treatment, BCR-ABL IS% correlated with immunological parameters such as plasma proteins, together with different memory subsets of CD4+ and CD8 + T cells. Interestingly, the proportion and cytotoxic potential of NK cells together with several soluble proteins increased during imatinib treatment. In contrast, no major immunological changes were observed during bosutinib treatment. In conclusion, imatinib and bosutinib were shown to have differential effects on the immune system in this randomized clinical trial. Increased number and function of NK cells were especially observed during imatinib therapy.

Detaljer

Författare
  • Anna Kreutzman
  • Bhagwan Yadav
  • Tim H. Brummendorf
  • Bjorn Tore Gjertsen
  • Moon Lee Hee
  • Jeroen Janssen
  • Tiina Kasanen
  • Perttu Koskenvesa
  • Kourosh Lofti
  • Berit Markevärn
  • Ulla Olsson-Strömberg
  • Jesper Stentoft
  • Leif Stenke
  • Stina Söderlund
  • Lene Udby
  • Johan Richter
  • Henrik Hjorth-Hansen
  • Satu Mustjoki
Enheter & grupper
Externa organisationer
  • University of Helsinki
  • Universitätsklinikum der RWTH Aachen
  • Haukeland University Hospital
  • VU University Medical Center
  • Linköping University
  • Norrland University Hospital
  • Uppsala University Hospital
  • Aarhus University Hospital
  • Karolinska University Hospital
  • Skåne University Hospital
  • St. Olav’s University Hospital
  • Norwegian University of Science and Technology
  • University of Bergen
  • Östergötland County Council
  • Uppsala universitet
  • Karolinska Institute
  • Zealand University Hospital
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Hematologi

Nyckelord

Originalspråkengelska
Artikelnummere1638210
TidskriftOncoImmunology
Volym8
Utgåva nummer9
StatusPublished - 2019 jul 13
PublikationskategoriForskning
Peer review utfördJa