In:
Blood Cancer Journal, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-01-28)
Kurzfassung:
Hypomethylating agents (HMA) like azacitidine are licensed for the treatment of acute myeloid leukemia (AML) patients ineligible for allogeneic hematopoietic stem cell transplantation. Biomarker-driven identification of HMA-responsive patients may facilitate the choice of treatment, especially in the challenging subgroup above 60 years of age. Since HMA possesses immunomodulatory functions that constitute part of their anti-tumor effect, we set out to analyze the bone marrow (BM) immune environment by next-generation sequencing of T cell receptor beta ( TRB ) repertoires in 51 AML patients treated within the RAS-AZIC trial. Patients with elevated pretreatment T cell diversity (11 out of 41 patients) and those with a boost of TRB richness on day 15 after azacitidine treatment (12 out of 46 patients) had longer event-free and overall survival. Both pretreatment and dynamic BM T cell metrics proved to be better predictors of outcome than other established risk factors. The favorable broadening of the BM T cell space appeared to be driven by antigen since these patients showed significant skewing of TRBV gene usage. Our data suggest that one course of AZA can cause reconstitution to a more physiological T cell BM niche and that the T cell space plays an underestimated prognostic role in AML. Trial registration : DRKS identifier: DRKS00004519
Materialart:
Online-Ressource
ISSN:
2044-5385
DOI:
10.1038/s41408-022-00615-7
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2022
ZDB Id:
2600560-8
