Clinical features and outcomes of patients with follicular lymphoma: A real-world study of 926 patients in China
Fenghua GaoTingting ZhangXia LiuZhenjie QuXianming LiuLanfang LiLihua QiuZhengzi QianShiyong ZhouWenchen GongBin MengXiubao RenXianhuo WangHuilai Zhang
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The data about the clinical features and outcomes of Chinese patients with follicular lymphoma (FL) are limited. Here, we conducted a retrospective study to explore the initial treatment strategies and clinical outcomes of Chinese patients with FL in the real world.This study included FL patients who were newly diagnosed in Tianjin Medical University Cancer Institute and Hospital from March 2002 to August 2020.A total of 926 FL patients were enrolled. The median age was 54 years old, and the majority of the Chinese FL patients had advanced-stage disease and Eastern Cooperative Oncology Group(ECOG) <1 but less frequently infiltrated bone marrow. After a median of 38-month follow-up, the 5-year progressive-free survival (PFS) and overall survival (OS) of grade1-3a were 57.8% and 88.7%, respectively, which both are similar to those reported in previous Chinese and Western studies. The co-existence at diagnosis of FL and diffuse large B-cell lymphoma (DLBCL) components (FL/DLBCL) was associated with poor outcomes. The FL grades and proportion of DLBCL component in FL/DLBCL did not have an impact on PFS and OS. The most common regimen with great efficacy and risk-benefit was RCHOP-like followed by R maintenance regimen. The 5-year cumulative hazard of histological transformation (HT) was 4.7% (95% CI, 3.5-5.9); median time to transformation was 23.5 months (range, 2-146 months) after diagnosis. Three-year survival following transformation was 55% (95% CI, 40-70). Patients with stage III-IV, elevated β2 microglobulin (β2-MG), and B symptoms seemed to be more prone to progress within 24 months of frontline therapy (POD24). The FLIPI-2 showed the highest specificity to predict POD24, reflecting the prediction of correctly classifying as low-risk patients, but the FLIPI had the highest sensitivity to predict the risk of progression for critical patients.We revealed the clinical characteristics and outcomes of FL patients in the real world in China, which may provide novel data on prognostic factors and primary treatment of FL, applicable to routine clinical practice.Keywords:
Follicular lymphoma
Regimen
B symptoms
International Prognostic Index
The International Prognostic Index (IPI) is a clinical prognostic tool used for more than 20 years in the risk stratification of patients with de novo diffuse large B cell lymphoma (DLBCL) who rece...
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The International Prognostic Index (IPI) has been a powerful tool for predicting post-treatment outcomes and comparing results across clinical trials in diffuse large B-cell lymphoma (DLBCL) for more than 20 years. Given that rituximab has improved survival across all risk groups since the late 1990s, investigators have created a new prognostic model based on a retrospective analysis of 1650 newly diagnosed DLBCL patients who received induction rituximab-based chemotherapy from 2000 to 2010 at seven centers in the National …
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Follicular lymphoma is the most frequent low-grade lymphoma in western countries, accounting for 25% of all lymphoma cases (Tan & Horning, 2008). Although follicular lymphoma is generally considered a long lasting indolent disorder, survival duration is heterogeneous and precise prognostic evaluation in the Rituximab era is greatly needed (Johnston & Salles, 2008). The Follicular Lymphoma International Prognostic Index (FLIPI) was developed from the retrospective series of a collaborative international working party (Solal-Celigny et al, 2004) and was validated in independent series (Perea et al, 2005; Arcaini et al, 2006; Buske et al, 2006). The same working group recently proposed the Follicular Lymphoma International Prognostic Index 2 (FLIPI2), based on prospectively collected data: β2-microglobulin higher than the upper limit of normal, longest diameter of the largest involved node longer than 6 cm, bone marrow involvement, haemoglobin level lower than 120 g/l and age >60 years were independent predictive factors of progression-free survival (PFS). Using these variables, a prognostic model was devised to identify three groups with different risk levels (Federico et al, 2009). The present analysis aimed to validate the FLIPI2 prognostic score on a large cohort of patients with follicular lymphoma. Our study involved 498 patients consecutively diagnosed with follicular lymphoma between 1980 and 2008 in our Institution. In all cases the diagnosis was based on histological biopsy of pathological material. Diagnosis was made in line with the lymphoma classification in use at the time of diagnosis. 418 had all the parameters needed for FLIPI calculation. 280 patients had all the parameters needed for FLIPI2 calculation: of them 262 were diagnosed after 1995 and 190 were treated with Rituximab (101 received first-line treatment of Rituximab combined with chemotherapy). Continuous variables are summarized as median and range. Categorical variables are reported as count and relative frequency. Survival analysis was carried out using the Kaplan–Meier product-limit method. Overall survival (OS) and PFS was established according to Cheson's criteria (Cheson et al, 2007). Gehan's Wilcoxon test was used to compare survival rates in the different groups. To compare the performance of two predictors in terms of discriminatory power, the Harrell C statistics were used. The C statistic estimates the proportion of correct predictions, i.e. the proportion of all patient pairs in which the predictions and the outcome are concordant (Harrell et al, 1996). If the predicted survival time is greater for the patient who lived longer, the predictions for that pair are said to be concordant with the outcomes. The standard errors and the 95% Confidence Intervals of C statistics were empirically computed with 1000 bootstrap samples. The clinical features of the 498 patients with follicular lymphoma are given in Table SI. After a median follow-up of 4·7 years (range 1–21), 142 patients had died. For the entire series median OS was 12·6 years and the 3- and 5-year OS rates were 91% and 79%, respectively. Median PFS was 3·7 years and the 5- and 10-year PFS survivals rates were 60% and 44%, respectively (Fig SI). Using the FLIPI score, 210 patients (50%) were in the low risk group, 131 patients (31%) in the low-intermediate and 77 patients (19%) in the high risk group. With the FLIPI2 score, 58 patients (21%) of patients were in the low risk group, 166 patients (59%) in the low-intermediate and 56 patients (20%) in the high risk group (Table I). Distribution of FLIPI2 categories according to FLIPI are reported in Table SII. According to FLIPI, the 3-year PFS was 74% for the low risk group, 54% for the intermediate risk and 39% for the high risk group (P = 0·001). Median PFS was 6·8 years for the low risk group, 3·1 years for that of intermediate risk and 2·1 for the high risk group (P = 0·009) (Fig SII). 3-year OS was 98% for the low risk group, 95% for the intermediate risk and 89% for the high risk group (P = 0·009) (Fig SIII). Using FLIPI2, the 3-year PFS was 77% for patients classified as low risk, 61% for intermediate risk, and 39% for the high risk group (P = 0·001). Median PFS was not reached by the low risk group, and was 3·3 years for the intermediate risk and 2·4 years for the high risk group (P = 0·009) (Fig 1). The 3-year OS was 98% for the low risk group, 95% for the intermediate risk, and 89% for the high risk group (P = 0·009) (Fig SIV). PFS was also different in 3 FLIPI2 risk categories in patients treated with Rituximab (P = 0·009). Progression-free survival according to FLIPI2 in 280 patients with follicular lymphoma. Considering low risk FLIPI patients, PFS was statistically shorter for patients with a high β2-microglobulin level (Fig SV). FLIPI2 was also able to identify three risk categories with statistically different PFS in 139 patients of the FLIPI low risk category (Fig SVI). Applying Harrell C statistics to each parameter of two prognostic scores, FLIPI2 produced a more discriminating index compared to FLIPI (Table SIII). Follicular B-cell lymphoma is an indolent disease with a relatively long life expectancy. However, survival duration is quite heterogeneous, with a subset of patients experiencing a poorer outcome. Prognostic assessment at diagnosis is, therefore, an important part of the initial evaluation of follicular lymphoma patients as it allows a rational selection of patients that may benefit from more intensified treatments. In this report we have compared two prognostic indexes for follicular lymphoma (i.e. FLIPI and FLIPI2) in an attempt to determine the value of each of the models. The calculation of the OS and PFS rates according to the FLIPI and FLIPI2 scores strongly corroborate in an independent series of the two scores in detecting risk groups of follicular lymphoma patients. In our analysis, FLIPI2 was found to be somewhat superior to FLIPI: the parameters included in FLIPI2 showed the best performance with Harrell C statistics compared to the parameters of the FLIPI score. Interestingly, FLIPI2 was also able to stratify patients with good prognosis into three risk categories. In conclusion, this study showed in an independent series that the FLIPI2 score is a reproducible prognostic index of clinical utility for the initial prognostic assessment of patients with follicular lymphoma. We would like to thank professor Massimo Federico for helpful discussion. Fig SI. Overall survival and progression free survival of 498 patients with follicular lymphoma. Fig SII. Progression-free survival according to FLIPI in 418 patients with follicular lymphoma. Fig SIII. Overall survival according to FLIPI in 418 patients with follicular lymphoma. Fig SIV. Overall survival according to FLIPI2 in 280 patients with follicular lymphoma. Fig SV. Progression-free survival for FLIPI good risk patients (n = 152) according to b2-microglobulin level. Fig SVI. Progression-free survival for FLIPI low risk patients (n = 139) according to FLIPI2 risk categories. Table SI. Clinical features of 498 patients with follicular lymphoma. Table SII. Distribution of FLIPI and FLIPI2 in 279 patients with both indexes FLIPI and FLIPI2. Table SIII. Performances of FLIPI and FLIPI2 using Harrell C statistics. Please note: Wiley-Blackwell are not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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The International Prognostic Index (IPI) has been the basis for determining prognosis in patients with diffuse large B-cell lymphoma (DLBCL) for the past 20 years. The utility of the IPI must be reassessed in the era of immunochemotherapy. Seven risk factors at diagnosis were identified, and a maximum of 7 points were assigned to each patient. Four risk groups were created: low (0-1), low-intermediate (2-3), high-intermediate (4), and high (5-7). Using MYC and BCL-2 clinical data from the Drum Tower Hospital collected during the rituximab era, we performed a retrospective analysis of patients with DLBCL treated with R-CHOP and built an biological markers adjusted IPI with the goal of improving risk stratification.Clinical features from 60 adults with de novo DLBCL diagnosed from 2008-2013 were assessed for their prognostic significance. The IPI remains predictive, but it cannot identify the high-risk subgroup. Compared with the IPI, the MYC and BCL-2 adjusted-IPI (A-IPI) better discriminated patients in the high-risk subgroup (4-year overall survival [OS]: 33.3%) than did the IPI (4 year OS: 48.0%). In the era of R-CHOP treatment, MYC and BCL-2 adjusted-IPI is more powerful than the IPI for helping guide treatment planning and interpretation of clinical trials.
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Primary bone diffuse large B-cell lymphoma (PB-DLBCL) is a rare DLBCL location variant. We treated 76 PB-DLBCL patients by immuno-chemotherapy, resulting in an 84% sustained complete remission rate and a 78.9% survival over a 4.7-year median follow-up period. Ann Arbor stage IV and high age-adjusted international prognostic index were predictive of adverse outcome in univariate analysis. In multivariate analysis using a Cox model, only aa-IPI predicted long-term survival. While based on a limited number of cases, we suggested that radiotherapy may be useful as a consolidation modality in PB-DLBCL. We also suggested that positron emission tomography/CT scan should be interpreted with caution due to a persistent [18F]fluorodeoxyglucose [18FDG] uptake of bone lesions even after remission in some in PB-DLBCL patients. Our study based on a homogeneous cohort of PB-DLBCL patients confirmed the favorable outcome of this DLBCL variant and support the implementation of prospective clinical trials in this disease.
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The prognostic significance of the t(14;18) in diffuse large B-cell lymphoma is still controversial. To assess the impact of the t(14;18) on patient survival, we investigated 26 patients with diffuse large B-cell lymphoma for the presence of t(14;18). The t(14;18) was detected in 90.9% of patients with high international prognostic index score. The five-year overall survival was 0.0% and 68.75% in positive and negative cases of t(14;18) respectively. The detection of the t(14;18) combined with the international prognostic index score is a useful strategy for more appropriate risk stratification and prediction of outcome of patients with diffuse large B-cell lymphoma.
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The prognostic significance of the t(14;18) in diffuse large B-cell lymphoma is still controversial. To assess the impact of the t(14;18) on patient survival, we investigated 26 patients with diffuse large B-cell lymphoma for the presence of t(14;18). The t(14;18) was detected in 90.9% of patients with high international prognostic index score. The five-year overall survival was 0.0% and 68.75% in positive and negative cases of t(14;18) respectively. The detection of the t(14;18) combined with the international prognostic index score is a useful strategy for more appropriate risk stratification and prediction of outcome of patients with diffuse large B-cell lymphoma.
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