Patient-Specific Measurable Residual Disease Markers Predict Outcome in Patients With Myelodysplastic Syndrome and Related Diseases After Hematopoietic Stem-Cell Transplantation

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Patient-Specific Measurable Residual Disease Markers Predict Outcome in Patients With Myelodysplastic Syndrome and Related Diseases After Hematopoietic Stem-Cell Transplantation

Tobiasson, Magnus (author): Karolinska Institutet,Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.;Karolinska Inst, Ctr Hematol & Regenerat Med HERM, Dept Med Huddinge, Stockholm, Sweden

Pandzic, Tatjana (author): Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi

Illman, Johanna (author): Division of Hematology, Helsinki University Hospital, Comprehensive Cancer Center, Helsinki, Finland,Helsinki Univ Hosp, Comprehens Canc Ctr, Div Hematol, Helsinki, Finland

Nilsson, Lars (author): Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Lund, Sweden,Skane Univ Hosp, Dept Hematol Oncol & Radiat Phys, Lund, Sweden

Weström, Simone (author): Uppsala universitet,Karolinska Institutet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi

Ejerblad, Elisabeth (author): Uppsala universitet,Karolinska Institutet,Hematologi

Olesen, Gitte (author): Department of Hematology, Aarhus University Hospital, Aarhus, Denmark,Aarhus Univ Hosp, Dept Hematol, Aarhus, Denmark

Björklund, Andreas (author): Karolinska Institutet,Karolinska Univ Hosp Huddinge, Karolinska Comprehens Canc Ctr, Dept Cellular Therapy & Allogene Stem Cell Transp, Stockholm, Sweden

Olsnes Kittang, Astrid (author): Department of Medicine, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway,Haukeland Hosp, Dept Med, Bergen, Norway.;Univ Bergen, Dept Clin Sci, Bergen, Norway

Werlenius, Olle (author): Section of Hematology and Coagulation, Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden,Sahlgrens Univ Hosp, Dept Med, Sect Hematol & Coagulat, Gothenburg, Sweden

Lorentz, Fryderyk (author): Department of Hematology, Norrlands University Hospital, Umeå, Sweden,Norrlands Univ Hosp, Dept Hematol, Umeå, Sweden

Rasmussen, Bengt, 1970- (author): Örebro universitet,Institutionen för medicinska vetenskaper,Department of Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden,Örebro Univ, Fac Med & Hlth, Dept Med, Örebro, Sweden

Cammenga, Jörg (author): Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Lund, Sweden; Division of Molecular Medicine and Gene Therapy, Lund University, Lund, Sweden,Skane Univ Hosp, Dept Hematol Oncol & Radiat Phys, Lund, Sweden.;Lund Univ, Div Mol Med & Gene Therapy, Lund, Sweden

Weber, Duruta (author): Department of Hematology, Odense University Hospital, Odense, Denmark,Odense Univ Hosp, Dept Hematol, Odense, Denmark

Lindholm, Carolin (author): Department of Hematology, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Huddinge, Centre for Hematology and Regenerative Medicine (HERM), Karolinska Institute, Stockholm, Sweden,Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.;Karolinska Inst, Ctr Hematol & Regenerat Med HERM, Dept Med Huddinge, Stockholm, Sweden

Wiggh, Joel (author): Department of Hematology, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Huddinge, Centre for Hematology and Regenerative Medicine (HERM), Karolinska Institute, Stockholm, Sweden,Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.;Karolinska Inst, Ctr Hematol & Regenerat Med HERM, Dept Med Huddinge, Stockholm, Sweden

Dimitriou, Marios (author): Karolinska Institutet,Karolinska Inst, Ctr Hematol & Regenerat Med HERM, Dept Med Huddinge, Stockholm, Sweden

Moen, Ann Elin (author): Department of Hematology, Oslo University Hospital, Rikshospitalet, Oslo, Norway,Oslo Univ Hosp, Dept Hematol, Rikshosp, Oslo, Norway

Yip Lundström, Laimei (author): Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden,Karolinska Inst, Inst Environm Med, Div Biostat, Stockholm, Sweden

von Bahr, Lena (author): Section of Hematology and Coagulation, Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden,Sahlgrens Univ Hosp, Dept Med, Sect Hematol & Coagulat, Gothenburg, Sweden

Baltzer-Sollander, Karin (author): Department of Genetics, HUS Diagnostic Centre, Helsinki University Hospital and University of Helsinki, Helsinki, Finland,Helsinki Univ Hosp, HUS Diagnost Ctr, Dept Genet, Helsinki, Finland.;Univ Helsinki, Helsinki, Finland

Jädersten, Martin (author): Karolinska Institutet,Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.;Karolinska Inst, Ctr Hematol & Regenerat Med HERM, Dept Med Huddinge, Stockholm, Sweden

Kytölä, Soili (author): Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden,Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden

Walldin, Gunilla (author): Department of Medicine, Huddinge, Centre for Hematology and Regenerative Medicine (HERM), Karolinska Institute, Stockholm, Sweden,Karolinska Inst, Ctr Hematol & Regenerat Med HERM, Dept Med Huddinge, Stockholm, Sweden

Ljungman, Per (author): Karolinska Institutet,Karolinska Univ Hosp Huddinge, Karolinska Comprehens Canc Ctr, Dept Cellular Therapy & Allogene Stem Cell Transp, Stockholm, Sweden

Groenbaek, Kirsten (author): Department of Hematology, Rigshospitalet, Copenhagen, Copenhagen, Denmark,Rigshospitalet, Dept Hematol, Copenhagen, Denmark

Mielke, Stephan (author): Karolinska Institutet,Karolinska Univ Hosp Huddinge, Karolinska Comprehens Canc Ctr, Dept Cellular Therapy & Allogene Stem Cell Transp, Stockholm, Sweden.;Karolinska Inst, Dept Lab Med, Stockholm, Sweden

Jacobsen, Sten Eirik W. (author): Department of Medicine, Huddinge, Centre for Hematology and Regenerative Medicine (HERM), Karolinska Institute, Stockholm, Sweden,Karolinska Inst, Ctr Hematol & Regenerat Med HERM, Dept Med Huddinge, Stockholm, Sweden

Ebeling, Freja (author): Division of Hematology, Helsinki University Hospital, Comprehensive Cancer Center, Helsinki, Finland,Helsinki Univ Hosp, Comprehens Canc Ctr, Div Hematol, Helsinki, Finland

Cavelier, Lucia (author): Department of Genetics, HUS Diagnostic Centre, Helsinki University Hospital and University of Helsinki, Helsinki, Finland,Helsinki Univ Hosp, HUS Diagnost Ctr, Dept Genet, Helsinki, Finland.;Univ Helsinki, Helsinki, Finland

Smidstrup Friis, Lone (author): Department of Hematology, Rigshospitalet, Copenhagen, Copenhagen, Denmark,Rigshospitalet, Dept Hematol, Copenhagen, Denmark

Dybedal, Ingunn (author): Department of Hematology, Oslo University Hospital, Rikshospitalet, Oslo, Norway,Oslo Univ Hosp, Dept Hematol, Rikshosp, Oslo, Norway

Hellström-Lindberg, Eva (author): Department of Hematology, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Huddinge, Centre for Hematology and Regenerative Medicine (HERM), Karolinska Institute, Stockholm, Sweden,Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.;Karolinska Inst, Ctr Hematol & Regenerat Med HERM, Dept Med Huddinge, Stockholm, Sweden

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Karolinska Institutet Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden;Karolinska Inst, Ctr Hematol & Regenerat Med HERM, Dept Med Huddinge, Stockholm, Sweden (creator_code:org_t)

American Society of Clinical Oncology, 2024
2024
English.
In: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 42:12, s. 1378-1390

Related links:: https://urn.kb.se/re...; show more...; https://doi.org/10.1...; http://kipublication...; http://kipublication...; https://urn.kb.se/re...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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).

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Hematology

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By the university: Örebro University; Karolinska Institutet; Uppsala University

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