Patients with myelofibrosis who harbored multi-hit TP53 mutations were at increased risk for relapse, shorter survival, and leukemic transformation after hematopoietic stem cell transplant (HSCT), according to results of a study published in the Blood.
“TP53 mutations have been associated with poor outcomes in various hematologic malignancies,” the authors wrote in their report, “but no data exist on its role in patients with myelofibrosis undergoing HSCT.”
The study evaluated data from 349 patients with myelofibrosis who were undergoing their first HSCT between 1997 and 2021 from an international, multicenter cohort. There were 14% of patients in the cohort with a TP53 mutation, including 8.6% with multi-hit mutations. The median variant allele frequency was 20.3%.
There were 44% of patients with wild-type TP53 and 35% of patients with single- or multi-hit TP53 mutations who were considered high molecular risk. A complex karyotype was present among 7% of patients with wild-type TP53, none of the patients with single-hit TP53 mutation, and 47% of patients with multi-hit TP53 mutations. Favorable cytogenetics was present among 73%, 68%, and 50% of patients in the wild-type and single- and multi-hit TP53 groups, respectively.
The median overall survival (OS) was significantly shorter among patients with a TP53 mutation with a median of 1.5 years compared with 13.5 years among patients with wild-type TP53 (P <.001). Patients with multi-hit TP53 mutations demonstrated a 6-year OS of 25% compared with 56% with a single-hit mutation and 64% with the wild-type variant.
In a multivariate analysis, shorter OS was significantly associated with the presence of multi-hit TP53 mutations (hazard ratio [HR], 2.12; 95% CI, 1.29-3.49; P =.003), but not single-hit mutations (HR, 1.44; 95% CI, 0.69-3.01; P =.33). Intermediate (HR, 2.44; 95% CI, 1.25-4.79; P =.01), high (HR, 5.11; 95% CI, 2.60-10.03; P <.001)) or very high (HR, 7.53; 95% CI, 3.85-14.74; P <.001). Myelofibrosis Transplant Scoring System scores were also significantly associated with shorter OS. There was no association with myeloablative conditioning.
The cumulative incidence of relapse was 52% with multi-hit TP53 mutations compared with 17% for single-hit mutations and 21% for wild-type variant.
Leukemic transformation was significantly shorter for patients with TP53 mutations with a median of 0.7 and 0.5 years among patients with multi- or single-hit TP53 mutations compared with 2.5 years among patients with the wild-type variant. Of the patients who developed leukemic transformation, 80% harbored a multi-hit TP53 mutations compared with 29% who had wild-type TP53.
The authors concluded that “multi-hit TP53 mutations represents a very high-risk group in myelofibrosis patients undergoing HSCT, whereas single-hit TP53 alone showed similar outcome to non-mutated patients, informing prognostication for survival and relapse.”
Source: hematologyadvisor.com/home/...
Research article:
Impact of TP53 on outcome of patients with myelofibrosis undergoing hematopoietic stem cell transplantation
Full-text Source: ashpublications.org/blood/a...
