Pathogenic clonal mutations in donors may lead to the proliferation of the same mutations in recipients of hematopoietic stem cell transplantation (HSCT), according to research published in Science Translational Medicine. These mutations may also be linked to post-HSCT morbidity, though further study is necessary to determine this.

Although HSCT can be curative for several hematologic diseases, the procedure carries risk for a variety of post-treatment events. There has been some suggestion that these post-treatment issues are linked to clones of pathogenic mutations present in donor clones.

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The evidence suggests that most, if not all, people over the age of 50 harbor rare, potentially pathogenic hematopoietic clones, but the frequency of pathogenic clones among adolescents and young adults was previously unknown. Given that adolescents and young adults with leukemia tend to have different genomic mutations from elderly patients, adolescents and young adults may have altogether different clonal hematopoietic mutations than individuals more than 50 years old.

For this study, researchers evaluated whether adolescent and young adult donors carry hematopoietic clones with pathogenic mutations that may be undetectable using standard next-generation sequencing, as well as how often any such clones are transferred to HSCT recipients and any effects on the clones thereafter.

Error-corrected sequencing, which has a detection limit of at least 0.0001, was performed on 125 blood and marrow samples from 25 matched unrelated donors and their recipients. Eleven donors showed a median variant allele frequency of clonal mutations of 0.00247; the researchers further determined that 84.2% of the mutations were molecularly pathogenic, and 100% were engrafted in HSCT recipients. At 100 days post-HSCT, all recipients showed clonal expansion.

“We have shown that extremely rare, preexisting clones with pathogenic mutations engrafted the recipients regardless of their initial variant allele frequency,” the researchers concluded. “This pilot study interrogating the prevalence of rare clonal hematopoiesis in the adolescent and young adult population and examining what happens to these clones in unrelated HSCT recipients merits a much larger study with longer follow-up to correlate post-HSCT morbidities with transfer and persistence of donor clones.”


1.     Wong WH, Bhatt S, Trinkaus K, et al. Engraftment of rare, pathogenic donor hematopoietic mutations in unrelated hematopoietic stem cell transplantation [published online January 15, 2020]. Sci Transl Med. doi:10.1126/scitranslmed.aax6249