TY - JOUR
T1 - Mosaic chromosomal alterations in hematopoietic cells and clinical outcomes in patients with multiple myeloma
AU - Husby, Simon
AU - Tulstrup, Morten
AU - Harsløf, Mads
AU - Nielsen, Christian
AU - Haastrup, Eva
AU - Ebbesen, Lene Hyldahl
AU - Klarskov Andersen, Mette
AU - Pertesi, Maroulio
AU - Brieghel, Christian
AU - Niemann, Carsten U.
AU - Nilsson, Björn
AU - Szabo, Agoston Gyula
AU - Andersen, Niels Frost
AU - Abildgaard, Niels
AU - Vangsted, Annette
AU - Grønbæk, Kirsten
PY - 2024/11
Y1 - 2024/11
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Chromosome Aberrations
KW - Female
KW - Follow-Up Studies
KW - Hematopoietic Stem Cell Transplantation/methods
KW - Hematopoietic Stem Cells/metabolism
KW - Humans
KW - Male
KW - Middle Aged
KW - Mosaicism
KW - Multiple Myeloma/genetics
KW - Prognosis
KW - Transplantation, Autologous
KW - Treatment Outcome
U2 - 10.1038/s41375-024-02396-3
DO - 10.1038/s41375-024-02396-3
M3 - Journal article
C2 - 39223296
AN - SCOPUS:85202925673
SN - 0887-6924
VL - 38
SP - 2456
EP - 2465
JO - Leukemia
JF - Leukemia
IS - 11
ER -