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

A special issue of Current Oncology (ISSN 1718-7729).

Deadline for manuscript submissions: closed (15 November 2023) | Viewed by 2817

Special Issue Editor


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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
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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 Cancers.

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

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Published Papers (1 paper)

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Research

14 pages, 1531 KiB  
Article
Low-Frequency PPM1D Gene Mutations Affect Treatment Response to CD19-Targeted CAR T-Cell Therapy in Large B-Cell Lymphoma
by Katja Seipel, Michèle Frey, Henning Nilius, Dilara Akhoundova, Yara Banz, Ulrike Bacher and Thomas Pabst
Curr. Oncol. 2023, 30(12), 10463-10476; https://doi.org/10.3390/curroncol30120762 - 13 Dec 2023
Cited by 4 | Viewed by 2141
Abstract
Chimeric antigen receptor T (CAR T)-cell therapy has become a standard treatment option for patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). Mutations in the PPM1D gene, a frequent driver alteration in clonal hematopoiesis (CH), lead to a gain of [...] Read more.
Chimeric antigen receptor T (CAR T)-cell therapy has become a standard treatment option for patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). Mutations in the PPM1D gene, a frequent driver alteration in clonal hematopoiesis (CH), lead to a gain of function of PPM1D/Wip1 phosphatase, impairing p53-dependent G1 checkpoint and promoting cell proliferation. The presence of PPM1D mutations has been correlated with reduced response to standard chemotherapy in lymphoma patients. In this study, we analyzed the impact of low-frequency PPM1D mutations on the safety and efficacy of CD19-targeted CAR T-cell therapy in a cohort of 85 r/r DLBCL patients. In this cohort, the prevalence of PPM1D gene mutations was 20% with a mean variant allele frequency (VAF) of 0.052 and a median VAF of 0.036. CAR T-induced cytokine release syndrome (CRS) and immune effector cell-associated neuro-toxicities (ICANS) occurred at similar frequencies in patients with and without PPM1D mutations. Clinical outcomes were globally worse in the PPM1D mutated (PPM1Dmut) vs. PPM1D wild type (PPM1Dwt) subset. While the prevalent treatment outcome within the PPM1Dwt subgroup was complete remission (56%), the majority of patients within the PPM1Dmut subgroup had only partial remission (60%). Median progression-free survival (PFS) was 3 vs. 12 months (p = 0.07) and median overall survival (OS) was 5 vs. 37 months (p = 0.004) for the PPM1Dmut and PPM1Dwt cohort, respectively. Our data suggest that the occurrence of PPM1D mutations in the context of CH may predict worse outcomes after CD19-targeted CAR T-cell therapy in patients with r/r DLBCL. Full article
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