A Clinico-Genotypic Prognostic Index for De Novo Composite Diffuse Large B-Cell Lymphoma Arising from Follicular Lymphoma in Asian patients treated in the Rituximab Era

Abstract

Composite follicular lymphoma with diffuse large B-cell lymphoma (FL/DLBCL) is uncommonly found on lymph node biopsy and represents a rare haematological malignancy. We aim to examine clinicopathological features of patients with FL/DLBCL and investigate predictors of survival outcome. We included in our retrospective study patients with histologically-proven FL/DLBCL at diagnosis (n = 106) and who were subsequently treated with rituximab-based chemoimmunotherapy from 2002-2017 at the National Cancer Centre. The cohort consisted of 34 women and 72 men with a median age of 59 years (range, 24-82). In a multivariate model inclusive of known clinico-pathological parameters at diagnosis, advanced stage (p = 0.0136), presence of MYC and/or BCL6 rearrangement (p = 0.0376) and presence of B symptoms (p = 0.0405) were independently prognostic for worse overall survival (OS). The only remaining independent prognostic variables for worse OS after including first-line treatment data in the model were use of chemotherapy regimens other than R-CHOP (p = 0.0360) and lack of complete response to chemotherapy (p < 0.0001) besides the presence of B symptoms (p = 0.0022). We generated a Clinico-Genotypic Index by point-wise addition of all five adverse parameters (score of 0-1, 2, 3, 4-5) which revealed four prognostic risk groups with a predicted 5-year OS of 100%, 62%, 40% and 0% (p < 0.0001) accounting for 50.0%, 24.5%, 18.9% and 6.6% of the cohort respectively. We propose that R-CHOP should be the recommended first-line regimen for composite FL/DLBCL. Follicular lymphoma (FL) is among the most common subtype of non-Hodgkin lymphoma (NHL), accounting for over one-fifth of NHL worldwide 1 . It is a heterogeneous group of tumours that originate from centrocytes and centroblasts among germinal centre B cells 2 . It is also well-known that FL has a propensity to transform to diffuse large B-cell lymphoma (DLBCL) at a rate of approximately 3% per year for the first 15 years 3,4 . Histological transformation (HT) to DLBCL portends a poor prognosis with a median survival of 14 to 27 months 3,5,6 .Multiple studies have elucidated various clinical and molecular markers predicting for HT and overall survival (OS) post-HT. High-risk Follicular Lymphoma International Prognostic Index (FLIPI), grade 3 histology, stage III or IV disease, low serum albumin and high serum lactate dehydrogenase (LDH) levels are commonly cited as risk factors for HT 5,7-9 . Molecular alterations such as TP53 10 and CDKN2A/B mutations 11 , as well as www.nature.com/scientificreports www.nature.com/scientificreports/ 50.0%, 24.5%, 18.9% and 6.6% of the cohort, with a predicted 5-year OS of 100%, 62%, 40% and 0% and a predicted 5-year PFS of 81%, 60%, 41% and 0% respectively (p < 0.0001) (Table 7) (Fig. 3b).Using the CGI, we were able to more precisely stratify patients into 4 unique prognostic risk groups as compared to the 3 risk groups using the earlier initial prognostic model. Most patients initially categorised as low risk remained in the same group, with 3.3...

Nomogram for Predicting the Overall Survival of Adult Patients With Primary Gastrointestinal Diffuse Large B Cell Lymphoma: A SEER- Based Study

“…The second limitation of this study is its retrospective nature, data integrity, and homogeneity are not guaranteed. Nevertheless, the patient population is relatively sufficient, and the findings of prognostic factors are consistent with other studies (31,36,37). Finally, treatment regimens of included patients were unclear.…”

Diffuse large b-cell lymphoma of the ocular adnexa with flow cytometry analysis and review of the literature

“…It is also important to keep in mind that HT to DLBCL has been shown to be associated with a poor prognosis, with a median survival time of 14−27 months. 20 However, little is known about the contribution of FCM to the diagnosis of HT to DLBCL. In our case of HT of FL to DLBCL (Case 4), CD10 level was markedly high, being 65.5% higher than in other cases.…”