Patient-Specific Measurable Residual Disease Markers Predict Outcome in Patients With Myelodysplastic Syndrome and Related Diseases After Hematopoietic Stem-Cell Transplantation
(2024) In Journal of Clinical Oncology 42(12). p.1378-1390- Abstract
PURPOSE: Clinical relapse is the major threat for patients with myelodysplastic syndrome (MDS) undergoing hematopoietic stem-cell transplantation (HSCT). Early detection of measurable residual disease (MRD) would enable preemptive treatment and potentially reduced relapse risk.METHODSPatients with MDS planned for HSCT were enrolled in a prospective, observational study evaluating the association between MRD and clinical outcome. We collected bone marrow (BM) and peripheral blood samples until relapse, death, or end of study 24 months after HSCT. Patient-specific mutations were identified with targeted next-generation sequencing (NGS) panel and traced using droplet digital polymerase chain reaction (ddPCR).RESULTSOf 266 included... (More)
PURPOSE: Clinical relapse is the major threat for patients with myelodysplastic syndrome (MDS) undergoing hematopoietic stem-cell transplantation (HSCT). Early detection of measurable residual disease (MRD) would enable preemptive treatment and potentially reduced relapse risk.METHODSPatients with MDS planned for HSCT were enrolled in a prospective, observational study evaluating the association between MRD and clinical outcome. We collected bone marrow (BM) and peripheral blood samples until relapse, death, or end of study 24 months after HSCT. Patient-specific mutations were identified with targeted next-generation sequencing (NGS) panel and traced using droplet digital polymerase chain reaction (ddPCR).RESULTSOf 266 included patients, estimated relapse-free survival (RFS) and overall survival (OS) rates 3 years after HSCT were 59% and 64%, respectively. MRD results were available for 221 patients. Relapse was preceded by positive BM MRD in 42/44 relapses with complete MRD data, by a median of 71 (23-283) days. Of 137 patients in continuous complete remission, 93 were consistently MRD-negative, 39 reverted from MRD+ to MRD-, and five were MRD+ at last sampling. Estimated 1 year-RFS after first positive MRD was 49%, 39%, and 30%, using cutoff levels of 0.1%, 0.3%, and 0.5%, respectively. In a multivariate Cox model, MRD (hazard ratio [HR], 7.99), WHO subgroup AML (HR, 4.87), TP53 multi-hit (HR, 2.38), NRAS (HR, 3.55), and acute GVHD grade III-IV (HR, 4.13) were associated with shorter RFS. MRD+ was also independently associated with shorter OS (HR, 2.65). In a subgroup analysis of 100 MRD+ patients, presence of chronic GVHD was associated with longer RFS (HR, 0.32).CONCLUSIONAssessment of individualized MRD using NGS + ddPCR is feasible and can be used for early detection of relapse. Positive MRD is associated with shorter RFS and OS.
(Less)
- author
- organization
- publishing date
- 2024-04
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Clinical Oncology
- volume
- 42
- issue
- 12
- pages
- 13 pages
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- pmid:38232336
- scopus:85189800901
- ISSN
- 0732-183X
- DOI
- 10.1200/JCO.23.01159
- language
- English
- LU publication?
- yes
- id
- f29ffd88-6292-4fde-9c61-522706ba49b8
- date added to LUP
- 2025-01-14 14:31:36
- date last changed
- 2025-07-16 18:40:36
@article{f29ffd88-6292-4fde-9c61-522706ba49b8,
abstract = {{<p>PURPOSE: Clinical relapse is the major threat for patients with myelodysplastic syndrome (MDS) undergoing hematopoietic stem-cell transplantation (HSCT). Early detection of measurable residual disease (MRD) would enable preemptive treatment and potentially reduced relapse risk.METHODSPatients with MDS planned for HSCT were enrolled in a prospective, observational study evaluating the association between MRD and clinical outcome. We collected bone marrow (BM) and peripheral blood samples until relapse, death, or end of study 24 months after HSCT. Patient-specific mutations were identified with targeted next-generation sequencing (NGS) panel and traced using droplet digital polymerase chain reaction (ddPCR).RESULTSOf 266 included patients, estimated relapse-free survival (RFS) and overall survival (OS) rates 3 years after HSCT were 59% and 64%, respectively. MRD results were available for 221 patients. Relapse was preceded by positive BM MRD in 42/44 relapses with complete MRD data, by a median of 71 (23-283) days. Of 137 patients in continuous complete remission, 93 were consistently MRD-negative, 39 reverted from MRD+ to MRD-, and five were MRD+ at last sampling. Estimated 1 year-RFS after first positive MRD was 49%, 39%, and 30%, using cutoff levels of 0.1%, 0.3%, and 0.5%, respectively. In a multivariate Cox model, MRD (hazard ratio [HR], 7.99), WHO subgroup AML (HR, 4.87), TP53 multi-hit (HR, 2.38), NRAS (HR, 3.55), and acute GVHD grade III-IV (HR, 4.13) were associated with shorter RFS. MRD+ was also independently associated with shorter OS (HR, 2.65). In a subgroup analysis of 100 MRD+ patients, presence of chronic GVHD was associated with longer RFS (HR, 0.32).CONCLUSIONAssessment of individualized MRD using NGS + ddPCR is feasible and can be used for early detection of relapse. Positive MRD is associated with shorter RFS and OS.</p>}},
author = {{Tobiasson, Magnus and Pandzic, Tatjana and Illman, Johanna and Nilsson, Lars and Weström, Simone and Ejerblad, Elisabeth and Olesen, Gitte and Björklund, Andreas and Kittang, Astrid Olsnes and Werlenius, Olle and Lorentz, Fryderyk and Rasmussen, Bengt and Cammenga, Jörg and Weber, Duruta and Lindholm, Carolin and Wiggh, Joel and Dimitriou, Marios and Moen, Ann Elin and Yip Lundström, Laimei and Von Bahr, Lena and Baltzer-Sollander, Karin and Jädersten, Martin and Kytölä, Soili and Walldin, Gunilla and Ljungman, Per and Groenbaek, Kirsten and Mielke, Stephan and Jacobsen, Sten Eirik W. and Ebeling, Freja and Cavelier, Lucia and Smidstrup Friis, Lone and Dybedal, Ingunn and Hellström-Lindberg, Eva}},
issn = {{0732-183X}},
language = {{eng}},
number = {{12}},
pages = {{1378--1390}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Journal of Clinical Oncology}},
title = {{Patient-Specific Measurable Residual Disease Markers Predict Outcome in Patients With Myelodysplastic Syndrome and Related Diseases After Hematopoietic Stem-Cell Transplantation}},
url = {{http://dx.doi.org/10.1200/JCO.23.01159}},
doi = {{10.1200/JCO.23.01159}},
volume = {{42}},
year = {{2024}},
}