Central Nervous System Progression/Relapse in Mature T-and NK-Cell Lymphomas

Sep 28, 2026

Non-Hodgkin lymphomas show marked biological heterogeneity across mature B-, T-, and NK-cell subtypes. Mature T- and NK-cell neoplasms are frequently aggressive and comprise about 15% of NHL. In relapsed/refractory disease, outcomes are poor, and secondary CNS involvement correlates with higher mortality, though whether it independently worsens prognosis remains unclear. Potential risk factors include elevated lactate dehydrogenase and multiple extranodal sites. Evidence largely relies on small retrospective series, with no consistent proof that CNS-directed prophylaxis prevents CNS progression/relapse. Ongoing studies aim to define epidemiology and clinicopathologic risk factors to guide prophylactic and systemic therapy decisions.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages21

Reading Time53 min

AccessFree to download

Introduction

Disease heterogeneity and subtype framework

Prognosis and outcomes in PTCL

Clinical context: CNS progression/relapse in MTNKL

cancers Review Central Nervous System Progression/Relapse in Mature T-and NK-Cell Lymphomas Rahul S. Bhansali and Stefan K. Barta * Citation: Bhansali, R.S.; Barta, S.K. Central Nervous System Progression/Relapse in Mature Tand NK-Cell Lymphomas. Cancers 2023, 15, 925. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/cancers15030925](10.3390/cancers15030925) Academic Editor: David Wong Received: 20 December 2022 Revised: 27 January 2023 Accepted: 30 January 2023 Published: 1 February 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . Department of Medicine, Division of Hematology and Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA * Correspondence: [stefan.barta@pennmedicine.upenn.edu](stefan.barta@pennmedicine.upenn.edu); Tel.: +1-215-614-0037 Simple Summary: Mature T-and NK-cell neoplasms are a heterogeneous group of disease entities that comprise about 15% of non-Hodgkin lymphomas. These subtypes are often aggressive, especially in the relapsed/refractory setting. In particular, central nervous system progression/relapse is a rare but devastating outcome for these patients. Moreover, relative infrequency and heterogeneity of tumor biology have precluded the ability to establish standards of care for prophylaxis and treatment of patients with secondary central nervous system involvement. This review describes the epidemiology and risk factors of central nervous system progression/relapse in patients with mature T-and NK-cell lymphomas and discusses the role of prophylaxis and therapy. Abstract: Non-Hodgkin lymphomas (NHL) are cancers of mature B-, T-, and NK-cells which display marked biological heterogeneity between different subtypes. Mature T-and NK-cell neoplasms are an often-aggressive subgroup of NHL and make up approximately 15% of all NHL. Long-term follow up studies have demonstrated that patients with relapsed/refractory disease have dismal outcomes; in particular, secondary central nervous system (CNS) involvement is associated with higher mortality, though it remains controversial whether this independently confers worse outcomes or if it simply reﬂects more aggressive systemic disease. Possible risk factors predictive of CNS involvement, such asan elevated lactate dehydrogenase and more than two sites of extranodal involvement, may suggest the latter, though several studies have suggested that discrete sites of anatomic involvement or tumor histology may be independent risk factors as well. Ultimately, small retrospective case series form the basis of our understanding of this rare but devastating event but have not yet demonstrated a consistent beneﬁt of CNS-directed prophylaxis in preventing this outcome. Nonetheless, ongoing efforts are working to establish the epidemiology of CNS progression/relapse in mature T-and NK-cell lymphomas with the goal of identifying clinicopathologic risk factors, which may potentially help discern which patients may beneﬁt from CNS-directed prophylactic therapy or more aggressive systemic therapy. Keywords: T-cell; NK-cell; lymphoma; lymphocyte; relapse; progression; central nervous system; prophylaxis 1. Introduction Lymphomas are a heterogeneous group of blood cancers with over 70 subtypes deﬁned by the 2022 updates in classiﬁcations of lymphoid neoplasms from the World Health Organization [1,2] and International Consensus Classiﬁcation [3] . These can be broadly subcategorized into mature B-cell and mature T-and NK-cell neoplasms. In this review, we will use the terms mature T-and NK-cell lymphoma (MTNKL) and peripheral T-cell lymphoma (PTCL) interchangeably, unless otherwise speciﬁed

FAQs

How common is CNS progression/relapse in mature T- and NK-cell lymphomas?

CNS progression/relapse in mature T- and NK-cell lymphomas is described as rare and poorly defined compared with B-cell NHL, where reported incidence is higher.

What factors are associated with secondary CNS involvement?

Potential risk factors discussed include elevated lactate dehydrogenase and more than two sites of extranodal involvement, while other studies suggest anatomic sites or tumor histology may independently influence risk.

Is CNS-directed prophylaxis proven to prevent CNS involvement?

Current understanding is based mainly on small retrospective case series, and these studies have not yet demonstrated a consistent benefit of CNS-directed prophylaxis.

Sep 28, 2026

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