Molecular Subclusters of Follicular Lymphoma: A Report From the Uk's Haematological Malignancy Research Network

Abstract

= 43, 70, 124, by age respectively). All NHL sub-types were more common in males except for Mediastinal B-cell (PMBL) more common in females. For all NHLs combined, survival was not influenced by gender or age but differed by place of care. 2y OS of patients aged 15-24y treated at the 29 Consented Study hospitals was 86% and 74% at other, mostly smaller district hospitals, Hazard Ratio 1.75 (0.94, 3.26). Consented Study Cohort 392 patients were recruited , 15-19y (n = 111), 20-24y (n = 148), 25-29y (n = 133). 27 NHL sub-types were recorded. Presentation with advanced disease was common; of 104 DLBCLs, 15% had NCCI IPI score of 4-5 and 18% had ≥3 extranodal disease sites.Unexpected was frequent failure to respond to first-line therapy in DLBCL and PMBL. 8/81 (10%) DLBCLs with complete treatment records died with refractory disease and 9 (11%) required ≥2 lines to achieve remission. 4/60 (7%) PMBLs died with refractory disease and 19 (32%) remained PET positive after first-line chemotherapy, needing further chemotherapy or radiotherapy to achieve remission.There was variation between hospitals in treatment regimens used for individual diseases. The effect of treatment on survival being most marked for Burkitt's Lymphoma aged 15-24y. Of a total 32 cases, 23 were treated with (R)CODOX-M±IVAC, 7 died (OS 69%); 9 treated on the (R)FAB/LMB96 protocol, 1 died (OS 89%). This observation needs investigation in a randomised trial.Conclusions: NHL in teenage and young adult patients is challenging to manage. Advanced disease and resistance to first line treatment is common. Our findings support treatment of these cases guided by experienced cancer centres. The detailed information gained by this national collaboration provides the evidence base for future trials and treatment strategies.

Integrated single cell analysis reveals co-evolution of malignant B cells and the tumor microenvironment in transformed follicular lymphoma

“…Aiming to develop a predictive tFL tools, bulk sequencing studies have yielded little success (Crouch et al, 2021; Green et al, 2013; Kridel et al, 2016; Okosun et al, 2014; Pasqualucci et al, 2014) and our high precision single cell analysis could only identify cells with a transformed genotype in a subset of the pre-transformed FL biopsies. However, our observations suggest that a more promising avenue for tFL prediction might come from exploring phenotypic features of malignant cells and the composition and spatial architecture of the TME.…”