Posttransplant MRD and T-cell chimerism status predict outcomes in patients who received allografts for AML/MDS

Loke, Justin, McCarthy, Nicholas, Jackson, Aimee, Siddique, Shamyla, Hodgkinson, Andrea, Mason, John, Crawley, Charles, Gilleece, Maria, Peniket, Andrew, Protheroe, Rachel, Salim, Rahuman, Tholouli, Eleni, Wilson, Keith, Andrew, Georgia, Dillon, Richard, Khan, Naeem, Potter, Victoria, Krishnamurthy, Pramila, Craddock, Charles and Freeman, Sylvie 2023. Posttransplant MRD and T-cell chimerism status predict outcomes in patients who received allografts for AML/MDS. Blood Advances 7 (14) , pp. 3666-3676. 10.1182/bloodadvances.2022009493

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Abstract

Allogeneic stem-cell transplant allows for the delivery of curative graft-versus-leukemia (GVL) in patients with acute myeloid leukemia/myelodysplasia (AML/MDS). Surveillance of T-cell chimerism, measurable residual disease (MRD) and blast HLA-DR expression may inform whether GVL effectiveness is reduced. We report here the prognostic impact of these biomarkers in patients allografted for AML/MDS. One hundred eighty-seven patients from FIGARO, a randomized trial of reduced-intensity conditioning regimens in AML/MDS, were alive and relapse-free at the first MRD time-point and provided monitoring samples for flow cytometric MRD and T-cell chimerism, requested to month+12. Twenty-nine (15.5%) patients had at least 1 MRD-positive result posttransplant. MRD-positivity was associated with reduced overall survival (OS) (hazard ratio [HR], 2.18; P = .0028) as a time-varying Cox variable and remained significant irrespective of pretransplant MRD status in multivariate analyses (P < .001). Ninety-four patients had sequential MRD with T-cell chimerism results at months+3/+6. Patients with full donor T-cell chimerism (FDTC) had an improved OS as compared with patients with mixed donor T-cell chimerism (MDTC) (adjusted HR=0.4; P = .0019). In patients with MDTC (month+3 or +6), MRD-positivity was associated with a decreased 2-year OS (34.3%) vs MRD-negativity (71.4%) (P = .001). In contrast, in the group with FDTC, MRD was infrequent and did not affect the outcome. Among patients with posttransplant MRD-positivity, decreased HLA-DR expression on blasts significantly reduced OS, supporting this as a mechanism for GVL escape. In conclusion, posttransplant MRD is an important predictor of the outcome in patients allografted for AML/MDS and is most informative when combined with T-cell chimerism results, underlining the importance of a GVL effect in AML/MDS.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	American Society of Hematology
ISSN:	2473-9529
Date of First Compliant Deposit:	7 March 2024
Date of Acceptance:	28 March 2023
Last Modified:	15 Mar 2024 10:35
URI:	https://orca.cardiff.ac.uk/id/eprint/166940

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