Mosaic Chromosomal Alterations in Hematopoietic Cells and Clinical Outcomes in Patients with Multiple Myeloma

Overview

Journal Leukemia

Specialties Hematology
Oncology

Date 2024 Sep 2

PMID 39223296

Authors

Simon Husby

Morten Tulstrup

Mads Harslof

Christian Nielsen

Eva Haastrup

Lene Hyldahl Ebbesen

Mette Klarskov Andersen

Maroulio Pertesi

Christian Brieghel

Carsten U Niemann

Bjorn Nilsson

Agoston Gyula Szabo

Niels Frost Andersen

Niels Abildgaard

Annette Vangsted

Kirsten Gronbaek

Affiliations

Soon will be listed here.

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 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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