Controversies in central nervous system prophylaxis of high-risk diffuse large B-cell lymphoma

Abstract

Purpose of review Central nervous system (CNS) relapse in patients with diffuse large B-cell lymphoma (DLBCL) is an uncommon but devastating complication with an overall survival of less than 6 months. This article will review the recent updates on CNS prophylaxis including new potential advances in the identification of high-risk patients. Recent findings The identification of patients at a high risk of CNS relapse is based on clinical and biological features has improved over recent years; however, the of different CNS prophylaxis strategies including intrathecal chemotherapy and high-dose methotrexate have been recently questioned in several large retrospective studies. The analysis of cell-free circulating tumor DNA (ctDNA) in the cerebrospinal fluid has been shown to identify patients with a high risk of CNS involvement and work is ongoing to identify how this can be used as a prognostic biomarker. Summary Recent clinical retrospective data have questioned the effectiveness of intrathecal and high-dose methotrexate in the prevention of CNS relapse in high-risk DLBCL patients. The role of more sensitive methods to detect CNS involvement and the benefit of novel therapies in CNS relapse prevention are currently under evaluation.

Drug Selection and Posology, Optimal Therapies and Risk/Benefit Assessment in Medicine: The Paradigm of Iron-Chelating Drugs

“…The pharmacological aspects of medicinal drugs including the selection and application of effective dose protocols are critical for the treatment of patients in all diseases. For example, individual variations in drug responses [1], differences among populations [2], different drug formulations [3], single or multiple drug administration [4] and different routes of drug administration [5] all have different effects on treatments. Similarly, the need for optimal, target-specific therapies including drug combinations as well as other parameters will also effect overall treatments [6][7][8][9][10].…”