Azacitidine-induced reconstitution of the bone marrow T cell repertoire is associated with superior survival in AML patients.
Blood Cancer J
; 12(1): 19, 2022 01 28.
Article
in En
| MEDLINE
| ID: mdl-35091554
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Azacitidine
/
Bone Marrow
/
T-Lymphocytes
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Leukemia, Myeloid, Acute
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Antimetabolites, Antineoplastic
Type of study:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Aged
/
Aged80
/
Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Blood Cancer J
Year:
2022
Type:
Article
Affiliation country:
Germany