TP53 Mutasyonlu Akut Myeloid Lösemiye Genel Bakış: Tek Merkez, Gerçek Yaşam Verisi

Öz

Amaç: TP53 mutasyonlu akut myeloid lösemi (AML), agresif hastalık seyri, kemoterapi direnci ve kötü sağkalım sonuçlarıyla karakterize, yüksek riskli ve farklı bir moleküler alt grup olarak tanımlanır. Bu çalışma, TP53 mutasyonlu AML hastalarının klinik özelliklerini, tedavi yanıtlarını ve sağkalım sonuçlarını tek merkezden bir gerçek yaşam kohortunun analiziyle sunmaktadır. Gereç ve Yöntem: Ocak 2023 ile Ocak 2024 tarihleri arasında Ankara Etlik Şehir Hastanesi’nde TP53 mutasyonlu AML tanısı alan dokuz hastanın verileri retrospektif gözlemsel bir çalışmayla incelendi. Hastalar, hasta ile ilgili faktörlere bağlı olarak yoğun veya yoğun olmayan indüksiyon rejimleriyle tedavi edildi. Sitogenetik ve moleküler anomaliler kaydedildi ve tedavi yanıtları Avrupa Lösemi Ağı (ELN) 2022 kılavuzuna göre değerlendirildi. Birincil sonlanım noktası genel sağkalım idi. Bulgular: Tanı anındaki medyan yaş 65 olup, hastaların %55,5’i kadındı. Olguların %66,7’sinde kompleks karyotip gözlendi ve iki hastada çoklu-vuruş TP53 mutasyonları tespit edildi. Yoğun indüksiyon tedavisi (7+3) ile tedavi edilen hastaların %75’inde tam yanıta ulaşılırken, azasitidin-venetoklaks rejimi alan hastaların %60’ında tam veya kısmi yanıt elde edildi. Tanıdan sonraki 12 ay içinde altı hasta, çoğunlukla enfeksiyon nedeniyle hayatını kaybederken, hayatta kalan üç hasta allojeneik hematopoetik kök hücre nakli (AHKHN) yapılan hastalardı. Tüm kohortun ortanca genel sağkalımı 9 ay idi. AHKHN yapılan hastalarda genel sağkalım anlamlı şekilde daha uzundu (p=0,01). Sonuç: TP53 mutasyonlu AML’nin prognozu halen son derece kötü olmaya devam etmektedir ve bu durum hasta sonuçlarını iyileştirmek için yeni tedavi yaklaşımlarının geliştirilmesine acil ihtiyaç duyulduğunu göstermektedir. AHKHN potansiyel bir sağkalım faydası sunsa da, etkili köprüleme tedavileri ve nakil sonrası yönetim, bu yüksek riskli popülasyonda sonuçların iyileştirilmesinde kritiktir.

Anahtar Kelimeler

• Akut myeloid lösemi
• kök hücre nakli
• sağkalım
• tedavi
• TP53 mutasyonu

Overview of Acute Myeloid Leukemia with TP53 Mutation: Single Center, Real-Life Data

Öz

Objective: Acute myeloid leukemia (AML) with TP53 mutations represents a distinct and high-risk molecular subgroup characterized by aggressive disease progression, chemoresistance, and poor survival outcomes. This study provides a single-center analysis of clinical characteristics, treatment responses, and survival outcomes in a real-world cohort of patients with TP53-mutated AML. Material and Method: A retrospective observational study was conducted at Ankara Etlik City Hospital, analyzing nine patients diagnosed with TP53-mutated AML between January 2023 and January 2024. Patients were treated with intensive or less intensive induction regimens based on patient-related factors. Cytogenetic and molecular abnormalities were recorded, alongside treatment responses were assessed per the European Leukemia Net 2022 guidelines. The primary endpoint was overall survival. Results: The median age at diagnosis was 65 years, with 55.5% female patients. Complex karyotypes were observed in 66.7% of cases, and multi-hit TP53 mutations were identified in two patients. A complete response was achieved in 75% of patients treated with intensive induction therapy (7+3), while a complete or partial response was achieved in 60% of patients receiving the azacitidine-venetoclax regimen. Six patients died within 12 months, predominantly due to infection, while the three surviving patients underwent for allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median overall survival (OS) of the entire cohort was 9 months. Patients with TP53-mutated AML who underwent allo-HSCT exhibited significantly prolonged OS (p=0.01). Conclusion: The prognosisof TP53-mutated AML remains particularly poor, highlighting an urgent need for the development of novel therapeutic approaches to improve patient outcomes. While allo-HSCT offers a potential survival benefit, effective bridging therapies and post-transplant management are critical for improving outcomes in this high-risk population

Anahtar Kelimeler

• Acute myeloid leukemia
• stem cell transplantation
• survival
• TP53 mutation
• treatment

Destekleyen Kurum

No relevant financial support.

Etik Beyan

Per the principles outlined in the Declaration of Helsinki, the Institutional Review Board of the xxx Hospital reviewed and approved the study protocol (Date: 31-07-2024, Number: AEŞK-BADEK-2024-592).

Kaynakça

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