TY - JOUR
T1 - Patient-Specific Measurable Residual Disease Markers Predict Outcome in Patients With Myelodysplastic Syndrome and Related Diseases After Hematopoietic Stem-Cell Transplantation
AU - Tobiasson, Magnus
AU - Pandzic, Tatjana
AU - Illman, Johanna
AU - Nilsson, Lars
AU - Weström, Simone
AU - Ejerblad, Elisabeth
AU - Olesen, Gitte
AU - Björklund, Andreas
AU - Olsnes Kittang, Astrid
AU - Werlenius, Olle
AU - Lorentz, Fryderyk
AU - Rasmussen, Bengt
AU - Cammenga, Jörg
AU - Weber, Duruta
AU - Lindholm, Carolin
AU - Wiggh, Joel
AU - Dimitriou, Marios
AU - Moen, Ann Elin
AU - Yip Lundström, Laimei
AU - von Bahr, Lena
AU - Baltzer-Sollander, Karin
AU - Jädersten, Martin
AU - Kytölä, Soili
AU - Walldin, Gunilla
AU - Ljungman, Per
AU - Groenbaek, Kirsten
AU - Mielke, Stephan
AU - Jacobsen, Sten Eirik W
AU - Ebeling, Freja
AU - Cavelier, Lucia
AU - Smidstrup Friis, Lone
AU - Dybedal, Ingunn
AU - Hellström-Lindberg, Eva
PY - 2024/4/20
Y1 - 2024/4/20
N2 - 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.METHODS: Patients 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).RESULTS: Of 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).CONCLUSION: Assessment 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 (ClinicalTrials.gov identifier: NCT02872662).
AB - 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.METHODS: Patients 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).RESULTS: Of 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).CONCLUSION: Assessment 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 (ClinicalTrials.gov identifier: NCT02872662).
KW - Graft vs Host Disease/etiology
KW - Hematopoietic Stem Cell Transplantation/methods
KW - Humans
KW - Leukemia, Myeloid, Acute/genetics
KW - Myelodysplastic Syndromes/therapy
KW - Neoplasm Recurrence, Local/genetics
KW - Neoplasm, Residual/genetics
KW - Prognosis
KW - Prospective Studies
KW - Recurrence
KW - Retrospective Studies
UR - http://www.scopus.com/inward/record.url?scp=85189800901&partnerID=8YFLogxK
U2 - 10.1200/JCO.23.01159
DO - 10.1200/JCO.23.01159
M3 - Journal article
C2 - 38232336
SN - 0732-183X
VL - 42
SP - 1378
EP - 1390
JO - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
IS - 12
ER -