Mosaic chromosomal alterations in hematopoietic cells and clinical outcomes in patients with multiple myeloma.

Autor: Husby S; Department of Hematology, Rigshospitalet, Denmark, Copenhagen N, Denmark. simon.husby.01@regionh.dk.; Biotech Research and Innovation Centre, BRIC, University of Copenhagen, Copenhagen, Denmark. simon.husby.01@regionh.dk., Tulstrup M; Department of Hematology, Rigshospitalet, Denmark, Copenhagen N, Denmark.; Biotech Research and Innovation Centre, BRIC, University of Copenhagen, Copenhagen, Denmark., Harsløf M; Department of Hematology, Rigshospitalet, Denmark, Copenhagen N, Denmark.; Biotech Research and Innovation Centre, BRIC, University of Copenhagen, Copenhagen, Denmark., Nielsen C; Department of Clinical Immunology, Odense University Hospital, Odense, Denmark.; Centre for Cellular Immunotherapy of Haematological Cancer, Odense, Denmark., Haastrup E; Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark., Ebbesen LH; Department of Hematology, Aarhus University Hospital, Aarhus, Denmark., Klarskov Andersen M; Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark., Pertesi M; Division of Hematology and Transfusion Medicine, Lund University, Lund, Sweden., Brieghel C; Department of Hematology, Rigshospitalet, Denmark, Copenhagen N, Denmark., Niemann CU; Department of Hematology, Rigshospitalet, Denmark, Copenhagen N, Denmark., Nilsson B; Division of Hematology and Transfusion Medicine, Lund University, Lund, Sweden., Szabo AG; Department of Hematology, Rigshospitalet, Denmark, Copenhagen N, Denmark., Andersen NF; Department of Hematology, Aarhus University Hospital, Aarhus, Denmark., Abildgaard N; Hematology Research Unit, Department of Hematology, Odense University Hospital, and Department of Clinical Research, University of Southern Denmark, Odense, Denmark., Vangsted A; Department of Hematology, Rigshospitalet, Denmark, Copenhagen N, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Grønbæk K; Department of Hematology, Rigshospitalet, Denmark, Copenhagen N, Denmark.; Biotech Research and Innovation Centre, BRIC, University of Copenhagen, Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2024 Nov; Vol. 38 (11), pp. 2456-2465. Date of Electronic Publication: 2024 Sep 02.
DOI: 10.1038/s41375-024-02396-3
Abstrakt: Mosaic chromosomal alterations (mCAs) in hematopoietic cells increase mortality and risk of hematological cancers and infections. We investigated the landscape of mCAs and their clinical consequences in 976 patients with multiple myeloma undergoing high-dose chemotherapy and autologous stem cell support (ASCT) with median 6.4 years of follow-up. mCAs were detected in the stem cell harvest product of 158 patients (16.2%). Autosomal aberrations were found in 60 patients (6.1%) and affected all chromosomes. Loss of chromosome X was found in 51 females (12.7%) and loss of chromosome Y in 55 males (9.6%). Overall survival and progression were similar between carriers of autosomal mCAs and non-carriers. In contrast, female patients with loss of the X chromosome had longer overall survival (age-adjusted[a.a.] HR 0.54, 95% CI 0.32-0.93, p = 0.02), lower risk of progression (a.a. HR 0.55, 95% CI 0.35-0.87; p = 0.01), and better post-transplant response (higher degree of complete response (CR) or very good partial response (VGPR)). The reason for this substantial effect is unknown. Additionally, myeloma clones in the stem cell product was confirmed by mCA analysis in the few patients with multiple mCAs (n = 12 patients). Multiple mCAs conferred inferior overall survival (a.a. HR 2.0, 95% CI 1.02-3.84; p = 0.04) and higher risk of myeloma progression (a.a. HR 3.36, 95% CI 1.67-6.81; p < 0.001), which is presumed to be driven by suspected myeloma contaminants.
(© 2024. The Author(s).)
Databáze: MEDLINE
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