MRD as Biomarker for Response to Donor Lymphocyte Infusion after Allogeneic Hematopoietic Cell Transplantation in Patients with AML

Author:

Teich Katrin1,Stadler Michael1,Gabdoulline Razif1ORCID,Kandarp Jyoti1ORCID,Wienecke Clara1,Heida Bennet1,Klement Piroska1,Büttner Konstantin1,Venturini Letizia1,Wichmann Martin1,Puppe Wolfram2,Schultze-Florey Christian1ORCID,Koenecke Christian1,Beutel Gernot1,Eder Matthias1,Ganser Arnold1ORCID,Heuser Michael1ORCID,Thol Felicitas1

Affiliation:

1. Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, 30625 Hannover, Germany

2. Department of Virology, Hannover Medical School, 30625 Hannover, Germany

Abstract

Donor lymphocyte infusions (DLIs) can directly target leukemic cells through a graft-versus-leukemia effect and play a key role in the prevention and management of relapse after allogeneic hematopoietic cell transplantation (alloHCT). Predictors of response to DLIs are not well established. We evaluated measurable residual disease (MRD) before, 30 and 90 days after DLI treatment as biomarkers of response. MRD was assessed by next-generation sequencing in 76 DLI-treated acute myeloid leukemia patients. MRD status before DLI treatment was independently prognostic for event-free survival (EFS, p < 0.001) and overall survival (OS, p < 0.001). Within 90 days of DLI treatment, 73% of MRD+ patients converted to MRD− and 32% of patients without remission achieved remission. MRD status 90 days after DLI treatment was independently prognostic for the cumulative incidence of relapse (CIR, p = 0.011) and relapse-free survival (RFS, p = 0.001), but not for OS. To evaluate the role of DLI treatment in MRD− patients, 23 MRD− patients who received DLIs were compared with a control cohort of 68 MRD− patients not receiving DLIs. RFS (p = 0.23) and OS (p = 0.48) were similar between the two cohorts. In conclusion, MRD is prognostic before (EFS, OS) and after (CIR, RFS) DLI treatment and may help in the selection of patients who benefit most from DLIs.

Funder

DJCLS

Deutsche Krebshilfe

BMBF

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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