Prognostic Significance of Lymphopenia for Stratification of Patients with Follicular Lymphoma
The therapy of follicular lymphoma (FL) is guided by several prognostic indices, such as the Follicular Lymphoma International Prognostic Index (FLIPI). The retrospective analysis of 736 patients with FL presented below introduces a prognostic model combining FLIPI and absolute lymphopenia into an integrated FLIPI-L index. Absolute lymphopenia is crucial for stratifying patient OS and the risk of transformation.
Prognostic Indices and Risk Stratification of Patients with FL
Follicular lymphoma constitutes one third of all non-Hodgkin lymphomas in the Western Hemisphere. The therapy of FL is guided by several prognostic indices. The original Follicular Lymphoma International Prognostic Index (FLIPI) was composed of 5 clinicobiological criteria, classifying patients into groups with low (FLIPI score 0−1), intermediate (FLIPI score 2), and high (FLIPI score 3−5) risk. Other prognostic indices include the modified FLIPI (extended by cardiovascular risk) or molecular models based on the mutational status of 7 genes.
In several hematologic malignancies and solid tumors, absolute lymphopenia affects patient prognosis. Previous studies have suggested an adverse effect of lymphopenia on the overall survival (OS) of patients with FL. Therefore, a modified FLIPI-L index, extending FLIPI with the lymphopenia factor, was proposed to better predict the risk of disease progression or transformation.
Analysis Methodology
Patients with FL treated between January 1999 and April 2016 were retrospectively included in the analysis. Data on the clinicopathological characteristics of the disease, MYC gene mutational status, and possible disease transformation were extracted from medical records. Absolute lymphopenia was defined as a lymphocyte count < 1.0 × 109/l.
The primary endpoint of the study was overall survival. Survival analysis was performed using the Kaplan-Meier log-rank method. A proportional hazards model, integrating FLIPI and absolute lymphopenia, was created using the Cox proportional hazards model. By adding absolute lymphopenia to FLIPI, the prognostic FLIPI-L index was created.
Results
The analysis included 736 patients, with a median follow-up of 72 months. The 5-year survival of the entire patient cohort reached 81.3%, and the 10-year survival 67.3%. OS at 5 and 10 years was poorer in patients with lymphopenia (69.5% vs. 86.7%, and 51.0% vs. 74.0%, respectively; p < 0.01). OS of patients with combined FLIPI-L 0−1 (low risk), 2−3 (intermediate risk), and 4−6 (high risk) at 5 years was 94.5/89.0/61.0%, and at 10 years 83.9/68.5/34.5%. Based on univariate and multivariate analyses, lymphopenia was identified as an independent predictor of OS.
The combination of FLIPI and absolute lymphopenia into a simplified two-variable model was named the FLIPI-L prognostic index. In this model, FLIPI components are classically assessed with 5 points, and 1 point is awarded for absolute lymphopenia. FLIPI-L can distinguish patients with different OS (log-rank p < 0.01).
During follow-up, the disease transformed in 135 patients (18%). The median time to disease transformation was 32 weeks. Patients with transformation more often had reduced hemoglobin levels, elevated lactate dehydrogenase levels, and lymphopenia (48.9% vs. 27.5%; p < 0.001).
Conclusion
The results of this analysis suggest the key role of lymphopenia as a prognostic biomarker in patients with FL. Patients with lymphopenia have a poorer prognosis regardless of their risk category according to FLIPI. OS of patients with low risk according to FLIPI and concurrent lymphopenia is identical to OS of patients with intermediate risk according to FLIPI without lymphopenia. Similarly, patients with intermediate risk according to FLIPI and lymphopenia have a prognosis comparable to patients with high risk according to FLIPI without lymphopenia. These data suggest that FLIPI score alone is not a sufficient prognostic marker. Integration of FLIPI and lymphopenia into one prognostic index (FLIPI-L) enables better stratification of FL patients by OS and also allows for prediction of the risk of transformation into aggressive lymphoma.
(alz)
Source: Yang G., Mills M., Kim Y. et al. Enhancement of the Follicular Lymphoma International Prognostic Index (FLIPI) with lymphopenia (FLIPI-L): a predictor for overall survival and histologic transformation. Blood Cancer J 2020; 9 (12): 104, doi: 10.1038/s41408-019-0269-6.
Did you like this article? Would you like to comment on it? Write to us. We are interested in your opinion. We will not publish it, but we will gladly answer you.
