Dr Patel on the Impact of Donor-Engrafted Clonal Hematopoiesis on Outcomes With Auto-/Allo-HSCT

Shyam A. Patel, MD, PhD, assistant professor, University of Massachusetts Chan Medical School, discusses the impact of donor-engrafted clonal hematopoiesis on the risk of disease relapse and survival outcomes with allogeneic and autologous hematopoietic stem cell transplant (allo-HSCT; auto-HSCT) in patients with hematologic malignancies.

Patel and colleagues conducted a comprehensive meta-analysis and meta-regression to evaluate the impact of donor-derived clonal hematopoiesis and pretransplant clonal hematopoesis on patient outcomes with allo-HSCT and auto-HSCT, respectively. The investigation evaluated 9 studies on auto-HSCT and 5 with allo-HSCT.

Results showed distinct effects of donor-derived clonal hematopoiesis on clinical outcomes depending on the type of transplant, Patel begins. For patients who underwent auto-HSCT, the pre-transplant clonal hematopoiesis was associated with poorer outcomes across several clinical parameters, including overall survival (OS), progression-free survival (PFS), and an increased risk of therapy-related neoplasms, he reports. These findings indicate that pre-transplant clonal hematopoiesis is a significant negative prognostic factor in auto-HSCT, potentially due to the superior engraftment potential of mutated hematopoietic stem cells compared to their wild-type counterparts, which may lead to worse overall outcomes, Patel explains.

In contrast, the impact of donor-derived clonal hematopoiesis in allo-HSCT showed a more nuanced effect, Patel continues. Although the presence of clonal hematopoiesis did not significantly affect OS, PFS, or non-relapse mortality, it was associated with a decreased risk of disease relapse, he details. This suggests a potential beneficial role of donor-derived clonal hematopoiesis in the context of allo-HSCT, possibly due to a graft-vs-leukemia (GvL) effect that may enhance the antitumor activity of the graft, Patelsays.

Overall, the study highlights a bimodal effect of clonal hematopoiesis, Patel states. Although it is predictive of inferior outcomes with auto-HSCT, it may provide some protective benefits with allo-HSCT, Patel notes. This distinction underscores the need for tailored approaches in screening for clonal hematopoiesis based on the type of stem cell transplant, he emphasizes. For auto-HSCT, prospective CHIP screening of the donor appears crucial due to its association with adverse outcomes with pre-transplant clonal hematopoesis, whereas the utility of such screening is less clear and may not be as critical for those undergoing allo-HSCT, Patelconcludes.