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Peer-reviewedCC BY 4.0Frontiers in Oncology

Measurable residual disease in chronic lymphocytic leukemia in real-world clinical practice: a single-center experience from 2018–2025

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Abstract

PurposeMeasurable residual disease (MRD) is a prognostic marker in chronic lymphocytic leukemia (CLL), although its implementation in routine practice remains less established than in other hematologic malignancies. We evaluated the feasibility and prognostic value of MRD monitoring in a real-world cohort of patients with CLL.Materials and methodsWe retrospectively analyzed 177 unique patients (198 treated episodes) with newly diagnosed (ND) or relapsed/refractory (RR) CLL treated at a single institution between 2018 and 2025. A total of 749 peripheral blood (PB) samples and 64 bone marrow aspirates were assessed using standardized 8-color flow cytometry according to European Research Initiative on CLL (ERIC) recommendations. Undetectable MRD (uMRD) was defined as the absence of detectable CLL cells at a sensitivity of <10−4. Progression-free survival (PFS) was analyzed according to MRD status.ResultsThe median limit of detection in PB was 0.0032%. Undetectable MRD in PB was achieved in 56% (111/198) of patients, most commonly after venetoclax-based therapy (73.0%; 81/111). The rate of uMRD was higher in ND than in RRCLL (62.0% vs. 47.5%). In ND setting, uMRD was associated with prolonged PFS compared with detectable MRD (median PFS 58.0 vs. 34.7 months; HR 2.28, 95% CI 1.20–4.32; p=0.012). No significant PFS difference according to MRD status was observed in the overall RRCLL cohort (HR 1.86, 95% CI 0.81–4.27; p=0.14), consistent with the substantial use of continuous BTKi monotherapy (38%; 31/80). Among biologically high-risk subgroups, the prognostic impact of MRD was particularly evident in patients with unmutated IGHV (HR 2.58, 95% CI 1.57–4.23; p<0.001).ConclusionsOur results confirm that MRD status may serve as a prognostic marker for patients treated with time-limited venetoclax-based regimens. We demonstrate that longitudinal MRD monitoring is feasible in routine clinical practice, supporting the growing role of MRD assessment in treatment optimization and response evaluation in CLL.

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BibTeX
@article{mihalyova2026measurable,
  title = {{Measurable residual disease in chronic lymphocytic leukemia in real-world clinical practice: a single-center experience from 2018–2025}},
  author = {Jana Mihalyova and Klara Lancova and Ingrid Kovacova and Kamila Kutejova and David Zihala and Jana Zuchnicka and Michaela Hornakova and Viktor Kubala and Katarina Hradska and Katerina Benkova and Lucie Broskevicova and Michal Kascak and Ivo Demel and Jaromir Gumulec and Tomas Jelinek and Roman Hajek},
  journal = {Frontiers in Oncology},
  year = {2026},
  month = nov,
  doi = {10.3389/fonc.2026.1918537},
  url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1918537},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Measurable residual disease in chronic lymphocytic leukemia in real-world clinical practice: a single-center experience from 2018–2025
AU  - Jana Mihalyova
AU  - Klara Lancova
AU  - Ingrid Kovacova
AU  - Kamila Kutejova
AU  - David Zihala
AU  - Jana Zuchnicka
AU  - Michaela Hornakova
AU  - Viktor Kubala
AU  - Katarina Hradska
AU  - Katerina Benkova
AU  - Lucie Broskevicova
AU  - Michal Kascak
AU  - Ivo Demel
AU  - Jaromir Gumulec
AU  - Tomas Jelinek
AU  - Roman Hajek
PY  - 2026
DA  - 2026/11/02
JO  - Frontiers in Oncology
DO  - 10.3389/fonc.2026.1918537
UR  - https://www.frontiersin.org/articles/10.3389/fonc.2026.1918537
AB  - PurposeMeasurable residual disease (MRD) is a prognostic marker in chronic lymphocytic leukemia (CLL), although its implementation in routine practice remains less established than in other hematologic malignancies. We evaluated the feasibility and prognostic value of MRD monitoring in a real-world cohort of patients with CLL.Materials and methodsWe retrospectively analyzed 177 unique patients (198 treated episodes) with newly diagnosed (ND) or relapsed/refractory (RR) CLL treated at a single institution between 2018 and 2025. A total of 749 peripheral blood (PB) samples and 64 bone marrow aspirates were assessed using standardized 8-color flow cytometry according to European Research Initiative on CLL (ERIC) recommendations. Undetectable MRD (uMRD) was defined as the absence of detectable CLL cells at a sensitivity of <10−4. Progression-free survival (PFS) was analyzed according to MRD status.ResultsThe median limit of detection in PB was 0.0032%. Undetectable MRD in PB was achieved in 56% (111/198) of patients, most commonly after venetoclax-based therapy (73.0%; 81/111). The rate of uMRD was higher in ND than in RRCLL (62.0% vs. 47.5%). In ND setting, uMRD was associated with prolonged PFS compared with detectable MRD (median PFS 58.0 vs. 34.7 months; HR 2.28, 95% CI 1.20–4.32; p=0.012). No significant PFS difference according to MRD status was observed in the overall RRCLL cohort (HR 1.86, 95% CI 0.81–4.27; p=0.14), consistent with the substantial use of continuous BTKi monotherapy (38%; 31/80). Among biologically high-risk subgroups, the prognostic impact of MRD was particularly evident in patients with unmutated IGHV (HR 2.58, 95% CI 1.57–4.23; p<0.001).ConclusionsOur results confirm that MRD status may serve as a prognostic marker for patients treated with time-limited venetoclax-based regimens. We demonstrate that longitudinal MRD monitoring is feasible in routine clinical practice, supporting the growing role of MRD assessment in treatment optimization and response evaluation in CLL.
SN  - 2234-943X
ER  -