TP53 and Complex Karyotype Are High-Risk Factors in HSCT for Myelofibrosis

A recent analysis showed that TP53 and complex karyotype are very high-risk factors in patients with myelofibrosis undergoing hematopoietic stem cell transplantation (HSCT). The results could help inform prognosis and patient counseling, according to research presented at the 2022 ASH Annual Meeting.

“TP53 mutations have been associated with poor outcomes in various hematologic malignancies, but no data exist on its role in patients with myelofibrosis undergoing HSCT,” wrote the authors, led by Nico Gagelmann, MD, of the University Medical Center Hamburg-Eppendorf in Germany. “Although HSCT remains the only curative treatment for myelofibrosis and its numbers continue to increase worldwide, its inherent treatment-related morbidity and mortality make adequate patient counseling crucial.”

The researchers analyzed data from seven US and European centers on patients with myelofibrosis who were having their first HSCT. Of the 349 patients, 49 (13%) had detectable TP53 mutations and 36 (10%) had complex karyotype. In addition, the researchers used current methods for cytogenetic risk stratification: 248 (71%) had favorable cytogenetic risk, 79, (23%) had unfavorable risk, and 22 (6%) had very high-risk (n=22, 6%). Upon analysis, patients with TP53 mutations were heavily represented in the unfavorable cytogenetic risk category, as compared with wild-type cases (39% vs 20%). Patients with complex karyotype were also heavily represented in that category (29% vs 7%).

The researchers then analyzed overall survival (OS). Those with TP53 mutations had six-year OS of 35%, compared to 64% among those without the mutation. The analysis revealed no differences in OS according to the aforementioned cytogenetic risk stratification. Similarly, patients with complex karyotype had a median OS of 1.9 years versus 13.5 years among those with other karyotypes. Patients with TP53 mutations also had a significantly higher risk of relapse (35% vs 17%) as compared to patients with no mutation.

Reference

Gagelmann N, Badbaran A, Salit RB, et al. TP53 and complex karyotype represent a very high-risk group in myelofibrosis undergoing hematopoietic stem cell transplantation: an international collaborative analysis. Abstract #340. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.