Prognostic impact of high-grade transformation in low-grade B-cell lymphomas: a systematic review and meta-analysis

Low-grade B-cell lymphomas generally follow an indolent course. Nonetheless, they can occasionally transform into high-grade lymphoma, leading to reduced survival. Despite therapeutic advances that have improved absolute survival in high-grade transformation (HGT) lymphomas, additional survival data are needed for patients with HGT lymphoma. We aimed to perform a pooled analysis of hazard ratios (HRs) comparing HGT lymphoma with low-grade lymphoma and de novo diffuse large B-cell lymphoma (DLBCL) to obtain more robust estimates. Studies reporting overall survival (OS) data comparing HGT lymphoma with low-grade B-cell lymphoma without HGT or de novo DLBCL were identified through a database search (PubMed, Embase, Web of Science, MEDLINE, and the Cochrane Library). Articles were excluded if they met any of the following criteria: (1) not relevant to the study subject; (2) review articles, case reports, or errata; (3) non-English publications; (4) nonclinical studies; or (5) conference abstracts lacking sufficient data. Hazard ratios (HRs) were extracted and pooled. Thirty-eight datasets from 35 selected studies were pooled. The pooled HRs for OS comparing HGT with low-grade B-cell lymphoma were statistically significant and close to 2, regardless of tumor type and treatment era. In the rituximab era, the pooled HR analysis of OS comparing HGT with de novo DLBCL was statistically significant (HR = 1.12). HGT was associated with a consistently inferior prognosis in low-grade B-cell lymphomas, with an approximately twofold increase in mortality risk. The results of this analysis suggest the need for more effective therapeutic strategies for HGT lymphoma.