Patients with myelofibrosis (MF) and multihit TP53 mutations appear to have a poorer response to hematopoietic stem cell transplantation (HSCT), with a higher rate of relapse and shorter time to leukemic transformation, according to a recently published study in Blood.

Although TP53 gene mutations have been linked to high-risk disease, resistance to treatment, and rapid leukemic transformation in several myelodysplastic syndromes, its prognostic value in MF has not been fully elucidated, the researchers noted. Furthermore, its influence in the context of HSCT has not yet been reported, they added.

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“Here, we aimed to investigate the impact of [TP53 mutations] and cytogenetics on outcomes of patients with myelofibrosis undergoing HSCT, using a large collaborative international cohort,” the authors wrote.

Mutations in the selected patients were detected through next-generation sequencing. To further analyze the role of TP53 in the overall outcomes, the authors divided patients with TP53 mutations into a multihit group (patients with 2 or more distinct mutations) and a single-hit group. The primary endpoint of the study was overall survival, and secondary endpoints included leukemic transformation, nonrelapse mortality, and progression-free survival.

After a median 6-year follow-up, overall survival was 30% greater in patients without any TP53 mutations. Comparison between the multihit and single-hit groups revealed that the former had a median overall survival of 25% compared to 56% in the latter.

Similarly, patients with TP53 mutations had a significantly higher relapse rate than patients without TP53 mutations. The relapse rate of patients with a multihit configuration was 35% higher than that in the single-hit constellation group. Analysis of the rate of leukemic transformation revealed similar results.

The authors noted that despite the worse outcomes associated with multihit TP53 mutations, HSCT remains the best therapeutic alternative for these patients. However, the combination of venetoclax with hypomethylating has shown strong results and could serve as a potential bridge for patients with multihit TP53 mutations and HSCT.

“Our data are not only of immediate clinical relevance for the transplant and non-transplant community, but also highlight the need for translational and clinical studies focused on understanding the mechanism of [TP53 mutations] specifically in patients with myelofibrosis,“ the authors wrote.


Gagelmann N, Badbaran A, Salit RB, et al. Impact of TP53 on outcome of patients with myelofibrosis undergoing hematopoietic stem cell transplantation. Blood. Published online March 20, 2023. doi:10.1182/blood.2023019630