Haploidentical Donors Lead to Similar Results in TP53-Mutated AML

Patients with TP53-mutated acute myeloid leukemia (AML) achieve similar outcomes from allogeneic hematopoietic cell transplantation (allo-HCT) regardless of the donor type, a new report suggests.

The study, a retrospective analysis of more than 400 cases, found overall survival (OS), relapse incidence, and graft-versus-host disease (GVHD)-free survival were comparable whether the transplant came from a haploidentical donor, a matched sibling donor, or a 10/10 matched unrelated donor. The report was published in the American Journal of Hematology.¹

Allo-HCT is important for patients with high-risk AML, such as those with TP53 mutations, because conventional chemotherapy typically only extends survival by a few months, the authors noted. The only potentially curative option for these patients is allo-HCT, and the preferred situation is one in which a human leukocyte antigen (HLA)-matched sibling donor is available. However, that only happens about 30% of the time.² Matched unrelated donors are likewise only available in a minority of cases, the authors said, leaving many patients to use haploidentical donors (haplo-HCT).¹

Early evidence has suggested that haplo-HCT can produce similar outcomes to matched sibling donors and matched unrelated donors, even among high-risk patients.³

The researchers aimed to compare the performance of different types of allo-HCT, and so they consulted the European Society for Bone and Marrow Transplantation registry to retrospectively study patients with TP53 mutation who received their first allo-HCT while in their first complete remission.¹

The investigators identified 451 patients who met the study’s inclusion criteria. The patients each underwent their transplant between 2010 and 2021. Of those, 86 cases used haploidentical donors, 117 used matched siblings, and 248 used matched unrelated donors.

The authors found comparable results among patients in all 3 donor categories. For instance, the 2-year overall survival (OS) rate for the entire cohort was 37.9%, including 36.9% for matched unrelated donors, 33.9% among patients with matched sibling donors, and 46.7% for patients using haploidentical donors.

The overall 2-year relapse incidence was 49.9%, with a rate of 50.8% among patients with matched unrelated donors, 54.2% for patients with matched sibling donors, and 40.8% for patients with haploidentical donors.

Ten percent of donors had grade III-IV acute GVHD at Day 180, with rates of 9.1% for patients with matched unrelated donors, 10.1% for those with matched sibling donors, and 13.6% for patients with haploidentical donors.

Other outcomes, including chronic GVHD; leukemia-free survival; GVHD-free, relapse-free survival; and non-relapse mortality were also similar amongst the groups.

In a multivariate analysis, patients with more recent transplants had a lower risk of acute GVHD, and older patients had a higher risk. Karnofsky performance status scores below 90 were associated with a lower risk of chronic GVHD, and older age increased patients’ risk.

The authors noted that retrospective, real-world studies are essential in evaluating allo-HCT transplants because donor type cannot be prospectively selected. Still, they said the inherent limitations of retrospective, registry-based studies should be factored into the study’s interpretation. For instance, they said the variant allelic frequency of TP53 mutations was not available.

In summary, they said their findings show that the use of haploidentical donors is feasible and appears to have similar outcomes to other types of donors in this patient population.

“This finding has potential clinical relevance in this patient population,” they said.

References

1. Ru Y, Chen J, Ferhat AT, et al. Similar outcome with Haploidentical, matched sibling, or matched unrelated donor hematopoietic cell transplantation for adult patients with adverse-risk TP53-mutated acute myeloid leukemia in first remission: a comparative study from the Global Committee and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Am J Hematol. Published online September 10, 2025. doi:10.1002/ajh.70069

2. Gragert L, Eapen M, Williams E, et al. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N Engl J Med. 2014;371(4):339-348. doi:10.1056/NEJMsa1311707

3. Huang T, Xu L, Zhang X, et al. Haploidentical haematopoietic stem cell transplantation for TP53-mutated acute myeloid leukaemia. Br J Haematol. 2023;200(4):494-505. doi:10.1111/bjh.18538