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

Husby, Simon ; Tulstrup, Morten ; Harsløf, Mads ; Nielsen, Christian ; Haastrup, Eva ; Ebbesen, Lene Hyldahl ; Klarskov Andersen, Mette ; Pertesi, Maroulio LU ; Brieghel, Christian and Niemann, Carsten U. , et al. (2024) In Leukemia 38(11). p.2456-2465
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Leukemia
volume
38
issue
11
pages
10 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:39223296
  • scopus:85202925673
ISSN
0887-6924
DOI
10.1038/s41375-024-02396-3
language
English
LU publication?
yes
id
e105c223-2aec-44d6-9685-1c4c678056e3
date added to LUP
2024-12-16 10:30:58
date last changed
2025-07-01 02:23:06
@article{e105c223-2aec-44d6-9685-1c4c678056e3,
  abstract     = {{<p>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 &lt; 0.001), which is presumed to be driven by suspected myeloma contaminants.</p>}},
  author       = {{Husby, Simon and Tulstrup, Morten and Harsløf, Mads and Nielsen, Christian and Haastrup, Eva and Ebbesen, Lene Hyldahl and Klarskov Andersen, Mette and Pertesi, Maroulio and Brieghel, Christian and Niemann, Carsten U. and Nilsson, Björn and Szabo, Agoston Gyula and Andersen, Niels Frost and Abildgaard, Niels and Vangsted, Annette and Grønbæk, Kirsten}},
  issn         = {{0887-6924}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{2456--2465}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Leukemia}},
  title        = {{Mosaic chromosomal alterations in hematopoietic cells and clinical outcomes in patients with multiple myeloma}},
  url          = {{http://dx.doi.org/10.1038/s41375-024-02396-3}},
  doi          = {{10.1038/s41375-024-02396-3}},
  volume       = {{38}},
  year         = {{2024}},
}