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Advances in the Diagnosis, Prognosis and Treatment of Diffuse Large B-cell Lymphoma

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: 25 December 2024 | Viewed by 8018

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Special Issue Editor

Dr. Gustavo Tapia

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Guest Editor

Department of Pathology, Hospital Germans Trias i Pujol, Universidad Autonoma de Barcelona, 08193 Barcelona, Spain
Interests: hematopathology; lymphoma diagnosis; molecular pathology; lymphomagenesis; HIV-related lymphomas
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin (NHL) lymphoma and constitutes 25–35% of adult NHL in developed countries. In recent years, different morphological variants, molecular subtypes, and clinical–biological entities with an impact on prognosis and treatment have been described. However, there is still a group of DLBCL with heterogeneous features, and a better understanding of their biology is necessary for a precise diagnosis, prognostication, and personalized treatment.

In this Special issue, we aim to collect original and review articles focusing on recent advances in the diagnosis, molecular biology, prognostic factors, and management of DLBCL. We hope that this issue will help in further understanding the biology of DLBCL.

You may choose our Joint Special Issue in Current Oncology.

Dr. Gustavo Tapia
Guest Editor

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Keywords

no-Hodgkin lymphoma
diffuse large B-cell lymphoma
DLBCL
lymphoma treatment
lymphoma diagnosis
lymphoma prognosis
lymphoma biology

Published Papers (4 papers)

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Research

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13 pages, 1825 KiB

Open AccessArticle

Clinical Impact of Single Nucleotide Polymorphism in CD-19 on Treatment Outcome in FMC63-CAR-T Cell Therapy

by Katja Seipel, Mariesol Abbühl, Ulrike Bacher, Henning Nilius, Michael Daskalakis and Thomas Pabst

Cancers 2023, 15(11), 3058; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15113058 - 05 Jun 2023

Cited by 1 | Viewed by 1534

Abstract

Chimeric antigen receptor (CAR)-T cell therapy is effective in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) with response rates of 63–84% and complete response observed in 43–54%. Common germline variants of the target antigen CD19 may elicit different responses to CAR-T cell therapy. The CD19 gene single nucleotide polymorphism rs2904880 encoding leucine or valine at amino acid position 174 of the CD19 antigen was prevalent in 51% of the studied DLBCL patients. In a retrospective comparative analysis of clinical outcome, there were significant differences in CD19 L174 versus V174 carriers: the median time of progression-free survival was 22 vs. 6 months (p = 0.06), overall survival was 37 vs. 8 months (p = 0.11), complete response rates were 51% vs. 30% (p = 0.05), and refractory disease rates were 14% vs. 32% (p = 0.04). The single nucleotide polymorphism in CD19 was shown to influence the treatment outcome in FMC63-anti-CD19-CAR-T cell therapy, and the CD19 minor allele L174 predicted a favorable treatment outcome. Full article

(This article belongs to the Special Issue Advances in the Diagnosis, Prognosis and Treatment of Diffuse Large B-cell Lymphoma)

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Graphical abstract

12 pages, 940 KiB

Open AccessArticle

ctDNA Is Useful to Detect Mutations at Codon 641 of Exon 16 of EZH2, a Biomarker for Relapse in Patients with Diffuse Large B-Cell Lymphoma

by José Díaz-Chávez, Olga Gutiérrez-Hernández, Lucia Taja-Chayeb, Sindy Gutiérrez-Chavarría, Alejandro Avilés-Salas and Myrna Candelaria

Cancers 2022, 14(19), 4650; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14194650 - 24 Sep 2022

Viewed by 1401

Abstract

(1) Background: The epigenetic regulator EZH2 is a subunit of the polycomb repressive complex 2 (PRC2), and methylates H3K27, resulting in transcriptional silencing. It has a critical role in lymphocyte differentiation within the lymph node. Therefore, mutations at this level are implicated in lymphomagenesis. In fact, the mutation at the Y641 amino acid in the EZH2 gene is mutated in up to 40% of B-cell lymphomas. (2) Methods: We compared the presence of exon 16 EZH2 mutations in tumor samples and ctDNA in a prospective trial. These mutations were determined by Sanger sequencing and ddPCR. (3) Results: One hundred and thirty-eight cases were included. Ninety-eight were germinal center, and twenty had EZH2 mutations. Mean follow-up (IQR 25–75) was 23 (7–42) months. The tumor samples were considered the standard of reference. Considering the results of the mutation in ctDNA by Sanger sequencing, the sensibility (Se) and specificity (Sp) were 52% and 99%, respectively. After adding the droplet digital PCR (ddPCR) analysis, the Se and Sp increased to 95% and 100%, respectively. After bivariate analysis, only the presence of double-hit lymphoma (p = 0.04) or EZH2 mutations were associated with relapse. The median Progression free survival (PFS) (95% interval confidence) was 27.7 (95% IC: 14–40) vs. 44.1 (95% IC: 40–47.6) months for the mutated vs. wild-type (wt) patients. (4) Conclusions: The ctDNA is useful for analyzing EZH2 mutations, which have an impact on PFS. Full article

(This article belongs to the Special Issue Advances in the Diagnosis, Prognosis and Treatment of Diffuse Large B-cell Lymphoma)

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Review

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17 pages, 394 KiB

Open AccessReview

Diffuse Large B-Cell Lymphoma in the HIV Setting

by Maria Huguet, José-Tomás Navarro, José Moltó, Josep-Maria Ribera and Gustavo Tapia

Cancers 2023, 15(12), 3191; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15123191 - 15 Jun 2023

Cited by 2 | Viewed by 1648

Abstract

Despite the widespread use of combined antiretroviral therapy (cART) and the subsequent decrease in AIDS-defining cancers, HIV-related lymphomas remain a leading cause of morbidity and mortality in people with HIV (PWH). Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL) subtype in PWH. This lymphoma is a heterogeneous disease including morphological variants and molecular subtypes according to the cell of origin or the mutation profile. In the pre-cART era, treatment with standard-dose chemotherapy induced high rates of toxicity and outcomes were very poor. The introduction of cART and the incorporation of infection prophylaxis allowed the use of conventional intensive chemotherapy regimens used in the general population, such as R-CHOP or R-EPOCH. The use of cART during chemotherapy treatment was initially controversial due to the potential risk of adverse drug–drug interactions. However, the availability of current cART regimens with less potential to cause drug interactions and evidence that cART improves survival rates in NHL strongly support the use of cART in PWH with DLBCL. Consequently, interdisciplinary collaboration between HIV specialists and hemato-oncologists for the management of potential interactions and overlapping toxicities between antiretroviral and antineoplastic drugs is crucial for the optimal treatment of PWH with NHL. Full article

(This article belongs to the Special Issue Advances in the Diagnosis, Prognosis and Treatment of Diffuse Large B-cell Lymphoma)

34 pages, 8093 KiB

Open AccessReview

Large B-Cell Lymphomas in the 5th Edition of the WHO-Classification of Haematolymphoid Neoplasms—Updated Classification and New Concepts

by Katrin S. Kurz, Michaela Ott, Sabrina Kalmbach, Sophia Steinlein, Claudia Kalla, Heike Horn, German Ott and Annette M. Staiger

Cancers 2023, 15(8), 2285; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15082285 - 13 Apr 2023

Cited by 4 | Viewed by 2854

Abstract

The family/class of the large B-cell lymphomas (LBCL) in the 5th edition of the World Health Organization (WHO) classification of haematolymphoid tumors (WHO-HAEM5) features only a few major changes as compared to the 4th edition. In most entities, there are only subtle changes, many of them only representing some minor modifications in diagnostic terms. Major changes have been made in the diffuse large B-cell lymphomas (DLBCL)/high-grade B-cell lymphomas (HGBL) associated with MYC and BCL2 and/or BCL6 rearrangements. This category now consists of MYC and BCL2 rearranged cases exclusively, while the MYC/BCL6 double hit lymphomas now constitute genetic subtypes of DLBCL, not otherwise specified (NOS) or of HGBL, NOS. Other major changes are the conceptual merger of lymphomas arising in immune-privileged sites and the description of LBCL arising in the setting of immune dysregulation/deficiency. In addition, novel findings concerning underlying biological mechanisms in the pathogenesis of the different entities are provided. Full article

(This article belongs to the Special Issue Advances in the Diagnosis, Prognosis and Treatment of Diffuse Large B-cell Lymphoma)

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