Validation of Angioimmunoblastic T-Cell Lymphoma (AITL) Score in Korean AITL Patients

Background:

Angioimmunoblastic T cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma (PTCL), accounting for approximately 2% of all non-Hodgkin lymphoma and 20% of PTCLs. AITL generally displays aggressive clinical course and prognosis is poor with 5-year OS (Overall survival) rate of approximately 40%. The International Prognostic Index (IPI), Prognostic Index for PTCL (PIT), and Prognostic Index for AITL (PIAI) have been widely used for the prognostication of AITL patients. Recently, the international T-cell lymphoma project proposed a novel prognostic score, AITL score based on age, ECOG performance status (ECOG PS), serum CRP level and serum B2-microglobulin (B2-M) level. AITL score demonstrated better discriminant power compared with the IPI, PIT, and PIAI. However, the prognostic significance of AITL score has not been validated. In this study, we aim to validate the prognostic significance of AITL score in Korean AITL patients.

Methods:

Between March 2001 and August 2021, 98 patients who were newly diagnosed with AITL were identified in the database of the Asan lymphoma Registry, Asan Medical Center, Seoul, South Korea. After excluding patients with no baseline serum β2-microglobulin level (n=13) and CRP (n=4), 81 patients were included in this retrospective analysis. Key baseline characteristics including age, performance status, stage, serum CRP level, serum B2-M level were collected. The upper limit of normal (ULN) of serum CRP level and serum B2-M level are 6 mcg/mL and 2.4 mcg/mL, respectively. Overall survival (OS) was defined as time from diagnosis to any cause of death. Survival curves were estimated by Kaplan-Meier method and compared using log-rank test. In the multivariate analysis, variables exhibiting a potential association with survival (p < 0.5) in the univariate analysis were included.

Results:

The median age was 61 years (range, 28-83), 47 patients (58.0%) were male, 79 (97.5%) had advanced disease at diagnosis, and 77 (95.1%) had elevated B2-M levels. In addition, two patients (2.5%) had ECOG PS > 2, 31 (38.3%) had extranodal involvement > 1. With a median follow-up duration of 2.0 years, the median OS was 3.6 years.

A total 81 patients were found to be evaluable for the prognostic model. There was no significant difference in OS of patients stratified according to the AITL score, with 2-year OS of 44.4%, 59.2%, and 58.4% for patient with low-risk (0-1 risk factor, n=6, 7.4%), intermediate-risk (2 risk factors, n=43, 53.1%) and high-risk (3-4 risk factors, n=32, 39.5%) groups, respectively (p=0.7). The lack of prognostic significance of the AITL score was mainly due to the fact that most of the patients had elevated B2-M (n=77, 95.1%), and serum B2-M had no significant association with OS in the univariate analysis (HR: 2.44, 95% CI: 0.33-17.79, p=0.379). Thus, we reevaluated the prognostic significance of B2-M by using 2 times of the ULN (2 x ULN, 4.8 mcg/mL). Serum B2-M of > 2 x ULN was significantly associated with poor OS in the univariate analysis (HR: 3.38, 95% CI: 1.75-6.50, p<0.001), and its prognostic significance remained in the multivariate analysis (HR: 2.66, 95% CI:1.09-6.49, p=0.031). Thus, we modified the AITL score using 2 x ULN as a cut-off value for B2-M instead of 1 x ULN (modified AITL score). There was a significance difference in OS of patients according to the modified AITL score with 2-year OS rate of 73.5%, 57.2%, and 40.3% for patient with low-risk (0-1 risk factor, n=31, 38.3%), intermediate-risk (2 risk factors, n=24, 29.6%) and high-risk (3-4 risk factors, n=26, 32.1%) groups, respectively (p=0.004).

Conclusion:

The AITL score failed to be validated in Korean AITL patients due to the fact that most patients had B2-M of > 1 x ULN. Modified AITL score, which adjusted the B2-M cut-off to 2 x ULN provided significant risk stratification of the patients. The optimal cut-off value for B2-M in AITL patients should be validated in future studies.

No relevant conflicts of interest to declare.