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New research · Hematology
Blood · 4d
Cohort studyBlood · 2026

Characteristics of Donor and Recipient Clonal Hematopoiesis in Nonmyeloablative Transplant for Sickle Cell Disease.

Lachelle D Weeks, Donna S Neuberg, Emily M Limerick … Courtney D Fitzhugh
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HematologyCohort study

Sickle cell disease recipients had 3.8-fold higher odds of DNA Damage Response-mutant clonal hematopoiesis.

Characteristics of Donor and Recipient Clonal Hematopoiesis in Nonmyeloablative Transplant for Sickle Cell Disease.

Lachelle D Weeks … Courtney D Fitzhugh
Blood · 2026
Background

Sickle cell disease (sickle cell disease) is an inherited hemoglobinopathy characterized by chronic hemolytic anemia, painful vaso-occlusive episodes, and end-organ damage.

Results
3.8-fold
Sickle cell disease recipients had 3.8-fold higher odds of DNA Damage Response-mutant clonal hematopoiesis.
n = 98 individuals
More results

We used error-corrected DNA sequencing to detect clonal hematopoiesis variants at a variant allele fraction > 0.0005 in blood samples from 98 individuals with sickle cell disease and 72 non-sickle cell disease donor controls who underwent HCT at the NIH between July 2004 and June 2023.

More results

Following HCT, the proportion of sickle cell disease recipients with clonal hematopoiesis increased, driven primarily by mutations in DNMT3A/TET2 and TP53.

All cases of donor-derived clonal hematopoiesis involved DNMT3A/TET2 mutations, while persistent-recipient clonal hematopoiesis involved DNA Damage Response mutations.

“
Conclusion

Larger cohort studies are needed to identify risk factors for developing DDR-CH and MDS/AML in sickle cell disease and to optimize cellular therapy safety in this population.

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