Aarhus University Seal / Aarhus Universitets segl

Clonal evolution in patients developing therapy-related myeloid neoplasms following autologous stem cell transplantation

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Clonal hematopoiesis (CH) denotes somatic mutations in genes related to myeloid neoplasms present at any variant allele frequency (VAF). Clonal hematopoiesis is associated with increasing age and with a factor 6 increase in the risk of developing therapy-related myeloid neoplasms (tMNs) following autologous stem cell transplantation (ASCT). However, the impact of specific mutations on progression from CH to tMN has yet to be unraveled, and it remains unclear whether mutations directly impact or even drive the development of tMN. We performed deep sequencing in longitudinal samples from a cohort of 12 patients with either multiple myeloma or lymphoma who developed tMN following ASCT. Nine patients had one or more mutations that could be tracked longitudinally. Seven patients had clonal expansion from time of ASCT to diagnosis of tMN. Of these, six patients had CH at VAF < 2% at baseline. The median VAF of non-DNMT3A clones increased from 1% (IQR 0.7%-10.0%) at time of ASCT to 37% (IQR 17%-47%) at tMN diagnosis (P = 0.002), while DNMT3A clones showed quiescent trajectories (P = 0.625). Our data provide evidence to support the hypothesis that the development of tMN following ASCT is likely instigated by CH present at VAFs as low as 0.5%, detectable years before tMN onset.

Original languageEnglish
Book seriesBone Marrow Transplantation
Volume57
Issue3
Pages (from-to)460-465
Number of pages6
ISSN0951-3078
DOIs
Publication statusPublished - Mar 2022

See relations at Aarhus University Citationformats

ID: 260332765