Which Patients with Myelofibrosis Have the Highest Post-HSCT Relapse Rate?

Multihit TP53 mutations characterize a “very high-risk group” of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) in myelofibrosis, according to a recent study.

Nico Gagelmann, MD, of University Medical Center Hamburg-Eppendorf in Germany, and colleagues conducted the research and published their findings in Blood.

They conducted the research because mutated TP53 has been “associated with poor outcomes in various hematologic malignancies,” but “no data exist on its role” in patients with myelofibrosis undergoing HSCT.

Dr. Gagelmann and colleagues included an international, multicenter cohort of 349 patients with myelofibrosis in the study. They detected mutated TP53 in 49 (13%) patients, with 30 of those patients showing a multihit configuration. The median variant allele frequency was 20.3%.

Most patients (71%) had a “favorable” cytogenetic risk, while 23% had an “unfavorable” cytogenetic risk, and 6% had a “very high” cytogenetic risk. The study’s authors detected a complex karyotype in 36 patients (10%).

The median survival of patients with mutated TP53 was 1.5 years, significantly lower than the median survival of 13.5 years for patients with wild-type TP53 (P<.001). This “outcome was driven” by the multihit TP53 mutation constellation, Dr. Gagelmann and colleagues wrote. The six-year survival rate was 25% in patients with multihit TP53 mutations, 56% in those with a single-hit TP53 mutation, and 64% in those with wild-type TP53.

The “outcome was independent of current transplant-specific risk factors and conditioning intensity,” according to the study’s authors.

The cumulative incidence of relapse was 52% in patients with multihit TP53 mutations, 17% in those with single-hit TP53 mutations, and 21% in those with wild-type TP53.

Leukemic transformation occurred in 10 patients with mutated TP53 (20%), eight of whom had a multihit constellation. In patients with wild-type TP53, leukemic transformation occurred in seven patients (2%). The median time to leukemic transformation was 0.7 years for those with multihit TP53 mutations, while it was half a year in those with single-hit TP53 mutations, and 2.5 years for those with wild-type TP53.

“In summary, multihit TP53 [mutations] represents a very high-risk group in myelofibrosis patients undergoing HSCT, whereas single-hit TP53 [mutations] alone showed similar outcome to nonmutated patients, informing prognostication for survival and relapse together with current transplant-specific tools,” Dr. Gagelmann and colleagues concluded.

Reference

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