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Yi Chen¹, Jing Zheng¹, Yanyan Qiu¹

¹Fujian Medical University Union Hospital, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fuzhou, Fujian, China.

Frontiers in Oncology

|December 15, 2023

Abstract:

The aim of this study was to examine the characteristics and prognosis of patients with myelodysplastic syndrome (MDS) accompanied by TP53 abnormalities and explore potential prognostic factors and treatment responses. This retrospective analysis included 95 patients with MDS and TP53 abnormalities and 173 patients with MDS without TP53 abnormalities at the Fujian Medical University Union Hospital between January 2016 and June 2023. Among patients with TP53 abnormalities, 26 (27.4%) developed AML during the disease course, with a median transformation time of 5.7 months. Complex karyotypes were observed in 73.1% of patients, and the proportions of -5 or del(5q), -7 or del(7q), +8, and -20 or del(20q) were 81.8%, 54.5%, 30.7%, and 25.0%, respectively. These patients exhibited poor survival, with a median overall survival (OS) of 7.3 months, and had 1- and 2-year OS rates of 42.2% and 21.5%, respectively. The complete response rates for azacitidine monotherapy, venetoclax combined with azacitidine, decitabine monotherapy, and decitabine combined with low-dose chemotherapy were 9.1%, 41.7%, 37.5%, and 33.3%, respectively. Long-term survival was similar among the four treatment groups. Patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) had a median OS of 21.3 months, which trended to be longer than that of patients who did not undergo allo-HSCT (5.6 months; P = 0.1449). Patients with pulmonary infection at diagnosis experienced worse OS than those without pulmonary infection (2.3 months vs. 15.4 months; P < 0.0001). Moreover, 61.9% of patients with pulmonary infection had immune dysfunction, with a ratio of CD4+ to CD8+ T lymphocytes below two. Pulmonary infections and complex karyotypes were independent adverse prognostic factors for OS. In conclusion, TP53 abnormalities in patients with MDS were frequently accompanied by complex karyotypes, and treatments based on hypomethylating agents or venetoclax have limited efficacy. Pulmonary infections associated with immune dysfunction is associated with poor prognosis.

Insights

Myelodysplastic syndrome (MDS) with TP53 abnormalities often presents with complex karyotypes and poor prognosis. Treatments like azacitidine and venetoclax show limited efficacy, while pulmonary infections indicate worse outcomes.

Area of Science:

Hematology
Oncology
Genetics

Background:

Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell disorders.
TP53 gene mutations are associated with a high risk of transformation to acute myeloid leukemia (AML) and poor prognosis in MDS.
Understanding the clinical characteristics and prognostic factors of MDS with TP53 abnormalities is crucial for optimizing patient management.

Purpose of the Study:

To investigate the characteristics and prognosis of patients with MDS and TP53 abnormalities.
To identify potential prognostic factors and evaluate treatment responses in this patient cohort.
To compare outcomes between MDS patients with and without TP53 abnormalities.

Main Methods:

A retrospective analysis of 95 patients with MDS and TP53 abnormalities and 173 patients with MDS without TP53 abnormalities.
Data collected included clinical characteristics, cytogenetic abnormalities, treatment regimens, and survival outcomes.
Statistical analysis was performed to identify prognostic factors and compare treatment efficacy.

Main Results:

MDS patients with TP53 abnormalities frequently exhibited complex karyotypes (73.1%) and a high rate of AML transformation (27.4%) with a median time of 5.7 months.
These patients had significantly poorer overall survival (OS) (median 7.3 months) compared to those without TP53 abnormalities.
Complete response rates varied among treatments: azacitidine (9.1%), venetoclax + azacitidine (41.7%), decitabine (37.5%), and decitabine + low-dose chemotherapy (33.3%).
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) showed a trend towards improved OS (21.3 months vs. 5.6 months).
Pulmonary infection at diagnosis was a significant adverse prognostic factor (OS 2.3 months vs. 15.4 months), often associated with immune dysfunction.

Conclusions:

TP53 abnormalities in MDS are strongly linked to complex karyotypes and poor prognosis.
Current treatments including hypomethylating agents and venetoclax demonstrate limited efficacy in this subgroup.
Pulmonary infections, particularly those associated with immune dysfunction, represent a critical adverse prognostic factor requiring targeted management.

Read full analysis

Keywords:

immune dysfunction myelodysplastic syndrome prognosis pulmonary infection tumor protein 53

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