Inflammation-Based Glasgow Prognostic Score as an Independent Prognostic Factor in Patients with Angioimmunoblastic T-Cell Lymphoma
Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive subtype of peripheral T-cell lymphoma (PTCL) associated with a poor prognosis. Characterized by systemic symptoms such as lymphadenopathy, B symptoms (fever, night sweats, weight loss), hypergammaglobulinemia, and autoimmune phenomena, AITL presents significant clinical challenges due to its rapid progression and limited treatment efficacy. Recent research has focused on identifying biomarkers to improve risk stratification and guide therapeutic decisions. Among these, the Glasgow Prognostic Score (GPS), a systemic inflammation-based scoring system combining serum C-reactive protein (CRP) and albumin (ALB) levels, has emerged as a potential prognostic tool. This study evaluates the prognostic significance of GPS in AITL and compares its predictive utility with the established Prognostic Index for PTCL (PIT).
Study Design and Patient Characteristics
A retrospective cohort analysis was conducted on 106 patients diagnosed with AITL between 2009 and 2019 at two Chinese medical centers. The cohort had a median age of 63 years (range: 34–84), with 61.3% male patients. Advanced-stage disease (Ann Arbor stage III–IV) was present in 85.8% of cases, while 39.6% exhibited extranodal involvement and 18.9% had bone marrow infiltration. Common clinical features included elevated lactate dehydrogenase (LDH) levels (57.5%), anemia (61.3%), and B symptoms (17.9%). The PIT score, which incorporates age, performance status, LDH, and bone marrow involvement, categorized 45.3% of patients into the high-risk group (PIT 3–4).
The GPS was calculated using pre-treatment CRP and ALB levels:
- GPS 0: CRP ≤10 mg/L and ALB ≥35 g/L (28.3% of patients).
- GPS 1: Either CRP >10 mg/L or ALB <35 g/L (44.3%).
- GPS 2: Both CRP >10 mg/L and ALB <35 g/L (27.4%).
High GPS scores correlated significantly with older age (>60 years, P=0.002), advanced Ann Arbor stage (P<0.001), elevated LDH (P=0.003), low hemoglobin (P<0.001), low platelet counts (P=0.035), and high PIT scores (P<0.001).
Treatment Protocols and Response Rates
First-line chemotherapy regimens included CHOP or CHOP-like therapy (69.8%), EPOCH (20.8%), and GEMOX (9.4%). Patients with GPS 2 were more likely to receive EPOCH or GEMOX (37.9%) compared to GPS 0 (26.7%) and GPS 1 (27.7%). After initial treatment, 52.8% of the entire cohort achieved complete remission (CR). However, CR rates varied markedly by GPS: 73.3% for GPS 0, 46.8% for GPS 1, and 41.4% for GPS 2 (P=0.001).
Survival Outcomes and Prognostic Stratification
With a median follow-up of 50.5 months, the median overall survival (OS) and progression-free survival (PFS) were 52.7 months and 22.0 months, respectively. The estimated 5-year OS and PFS rates were 43.0% and 37.0% for the entire cohort.
GPS-Based Survival Analysis
- OS: Patients with GPS 0 exhibited a 5-year OS rate of 76.0%, compared to 43.4% for GPS 1 and 0% for GPS 2 (P<0.001).
- PFS: Similarly, 5-year PFS rates were 61.0% (GPS 0), 38.7% (GPS 1), and 0% (GPS 2) (P<0.001).
PIT Score Comparison
The PIT score also stratified survival outcomes:
- OS: 5-year OS was 57.4% for PIT 1–2 vs. 25.4% for PIT 3–4 (P=0.002).
- PFS: 5-year PFS was 46.1% for PIT 1–2 vs. 26.5% for PIT 3–4 (P=0.017).
Notably, GPS further refined prognosis within the PIT low-risk group (PIT 1–2). Patients with GPS 0 in this subgroup had superior 5-year OS (88.4%) and PFS (67.7%) compared to GPS 1 (46.5% OS; 39.6% PFS) and GPS 2 (0% for both) (P<0.001). However, GPS did not significantly differentiate outcomes in the high-risk PIT group (PIT 3–4).
Multivariate Analysis and Independent Prognostic Value
Univariate analysis identified age >60 years (P=0.017), elevated LDH (P=0.016), anemia (P=0.006), high GPS (P<0.001), and high PIT (P=0.002) as adverse factors for OS. In multivariate analysis, only GPS retained independent prognostic significance for both OS (hazard ratio [HR]: 5.702, 95% CI: 2.214–14.686, P<0.001) and PFS (HR: 3.324, 95% CI: 1.668–6.626, P=0.001).
Mechanistic Insights and Clinical Implications
The study hypothesizes that elevated GPS reflects a pro-inflammatory tumor microenvironment and systemic metabolic dysfunction. CRP, an acute-phase protein, indicates persistent inflammation driven by cytokines such as IL-6, which promote tumor growth and immune evasion. Hypoalbuminemia, a marker of malnutrition and chronic inflammation, may impair treatment tolerance and recovery. Furthermore, high GPS correlated with elevated LDH and advanced disease stage, suggesting it indirectly measures tumor burden and biological aggressiveness.
In clinical practice, GPS offers a simple, cost-effective tool to stratify AITL patients at diagnosis. Its superiority over PIT in the low-risk subgroup highlights its potential to guide personalized therapy, such as intensifying treatment for GPS 2 patients or de-escalating for GPS 0. However, the study’s retrospective design and single-region cohort limit generalizability, warranting validation in prospective, multicenter studies.
Conclusion
This study establishes the GPS as a robust, independent prognostic marker in AITL, outperforming the PIT score in low-risk patients. By integrating systemic inflammation and nutritional status, GPS provides a holistic view of disease biology and patient fitness, enhancing risk stratification and therapeutic decision-making. Future research should explore the biological pathways linking inflammation to AITL progression and evaluate GPS-guided treatment strategies.
doi.org/10.1097/CM9.0000000000001345
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