Multi-hit TP53MT impact on transplant outcome in myelofibrosis

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).

For patients with myelofibrosis undergoing hematopoietic stem cell transplantation, multi-hit TP53 mutations (TP53MT) are a very high risk group, while the outcomes of those developing single-hit TP53MT were similar to those without mutations, new research shows. The study included 349 patients, with TP53MT detected in 49, including 30 who had a multi-hit configuration. The median variant allele frequency was 20.3%, while cytogenic risk was favorable for 71%, unfavorable for 23%, and very high for 6%. Thirty-six patients (10%) had complex karyotypes. TP53MT patients had a 1.5-year median survival rate compared with 13.5 years for patients with TP53 wild-type (TP53WT). Six-year survival for multi-hit TP53MT patients was 25%, compared with 56% for single-hit TP53MT patients and 64% for TP53WT carriers. Transplant-specific risk factors and conditioning intensity did not affect outcomes. Single-hit TP53MT patients had a 17% cumulative incidence of relapse vs 52% for multi-hit TP53MT patients and 21% for TP53WT. Ten TP53MT patients had leukemic transformation soon after transplantation compared with seven TP53WT patients. Eight of 10 patients with TP53MT had a multi-hit configuration. The median time to leukemic transformation for multi-hit TP53MT, single-hit TP53MT, and TP53WT was 0.7 years, 0.5 years, and 2.5 years, respectively.

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Tags: hematology, Research, Science, abstract, mutation, results, hematopoietic transplantation