Primary Mediastinal DLBCL: Evolving Biologic Understanding and Therapeutic Strategies

Zinzani, Pier Luigi; Piccaluga, Pier Paolo

doi:10.1007/s11912-011-0189-5

Cited by 14 publications

(9 citation statements)

References 75 publications

(106 reference statements)

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“…Our results show that CD74 is highly expressed in PMBCL as previously reported in one study . PMBCL has specific clinical and pathological features related to overexpression of an NF‐κB activation signature and nuclear localization of NF‐κB transcription factor complexes . In normal B‐cells, CD74 signaling has been shown to promote cell survival through CD44/PI3K/AKT‐mediated NF‐κB activation.…”

Section: Discussionsupporting

confidence: 84%

High frequency of CD74 expression in lymphomas: implications for targeted therapy using a novel anti‐CD74‐drug conjugate

Song

Molina

et al. 2018

The Journal of Pathology CR

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CD74 is a type II transmembrane glycoprotein that functions as an MHC class II chaperone and displays diverse roles in immune responses. Recently, anti-CD74 immunotherapy has shown promise as an effective treatment strategy for lymphoid neoplasms in preclinical models. Using a human anti-CD74 antibody (SP7219), we defined the expression of CD74 protein in both normal and over 790 neoplastic hematolymphoid tissue samples. We found that CD74 is expressed broadly in normal B-cell compartments including primary and secondary lymphoid follicles and in the thymic medulla. The vast majority of lymphomas expressed CD74, including Hodgkin lymphomas (98%), B-cell lymphomas (96%), extranodal NK/T-cell lymphomas (88%), mature T-cell lymphomas (80%), and plasma cell myeloma (75%). Our findings confirm and expand previous observations regarding the expression of CD74 and suggest that CD74 expression on tumor cells may be directly targeted for immunomodulatory therapy for lymphoid and plasma cell malignancies.

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Section: Discussionsupporting

confidence: 84%

High frequency of CD74 expression in lymphomas: implications for targeted therapy using a novel anti‐CD74‐drug conjugate

Song

Molina

et al. 2018

The Journal of Pathology CR

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“…The clinical and pathological peculiarities of PMLBCL, the high chances of cure documented in literature in more than 20 years of international experience and the long disease-free life-expectancy of cured patients, have always drawn attention in finding out the most suitable first-line approach and the most convenient combination of treatment modalities, on the one hand trying to maximize the long-term clinical outcomes, while on the other reducing the potential harmful consequences of highly toxic combined treatments [20, 21]. …”

Section: Discussionmentioning

confidence: 99%

The treatment of primary mediastinal large B-cell lymphoma: a two decades monocentric experience with 98 patients

et al. 2017

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BackgroundThe purpose of this study is to investigate the most suitable first-line approach and the best combination treatment for primary mediastinal large B-cell lymphoma (PMLBCL) as they have been matter of debate for at least two decades.MethodsOur single centre experience in the treatment of 98 de novo PMLBCL patients over the last 20 years is reviewed. All patients received MACOP-B chemotherapy. Thirty-seven received both rituximab and mediastinal radiotherapy; 30 were irradiated after chemotherapy, although not receiving rituximab and 20 received rituximab without radiotherapy consolidation. Eleven patients received chemotherapy only.ResultsSixty-one (62.2%) patients achieved a complete response after MACOP-B (with or without rituximab); among the 27 (27.6%) partial responders, 21 obtained a complete response after radiotherapy. At the end of their scheduled treatment, 82 patients (83.7%) had a complete and 6 a partial response (6.1%). Eleven patients relapsed within the first 2 years of follow-up. The 17-year overall survival is 72.0% (15 patients died); progression-free and disease-free survival are 67.6% and 88.4%, respectively. A statistically significant difference in overall and progression-free survival was noted among treatment groups, although no disease-free survival difference was documented.ConclusionsOur data indicate that a third-generation regimen like MACOP-B could be considered a suitable first-line treatment. Mediastinal consolidation radiotherapy impacts on survival and complete response rates and remains a good strategy to convert partial into complete responses. Data suggest that radiotherapy may be avoided in patients obtaining a complete response after (immuno)chemotherapy, but this requires confirmation with further ad hoc studies.

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“…The application of more intensive regimens, such as dose adjusted EPOCH (DA-EPOCH-R), with the addition of rituximab appear to obviate the need for radiation, reducing long term complication. 75–77 …”

Section: Mediastinal (Thymic) Large B-cell Lymphoma (Pmbl)mentioning

confidence: 99%

The Histological and Biological Spectrum of Diffuse Large B-Cell Lymphoma in the World Health Organization Classification

2012

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Diffuse large B cell lymphomas (DLBCL) are aggressive B-cell lymphomas that are clinically, pathologically and genetically diverse, in part reflecting the functional diversity of the B-cell system. The focus in recent years has been towards incorporation of clinical features, morphology, immunohistochemistry and ever evolving genetic data into the classification scheme. The 2008 WHO classification reflects this complexity with the addition of several new entities and variants. The discovery of distinct subtypes by gene expression profiling (GEP) heralded a new era with a focus on pathways of transformation as well as a promise of more targeted therapies, directed at specific pathways. Some DLBCLs exhibit unique clinical characteristics with a predilection for specific anatomic sites; the anatomic site often reflects underlying biological distinctions. Recently, the spectrum of EBV-driven B-cell proliferations in patients without iatrogenic or congenital immunosuppression has been better characterized; most of these occur in patients of advanced age, and include EBV-positive large B-cell lymphoma of the elderly. HHV-8 is involved in the pathogenesis of primary effusion lymphoma, which can present as a “solid variant.” Two borderline categories were created; one deals with tumors at the interface between classical Hodgkin lymphoma (cHL) and DLBCL. The second confronts the interface between Burkitt Lymphoma (BL) and DLBCL, so called “B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma” in the 2008 classification. Most cases harbor both MYC and BCL2 translocations, and are highly aggressive. Another interesting entity is ALK+ DLBCL, which renders itself potentially targetable by ALK inhibitors. Ongoing investigations at the genomic level, with both exome and whole genome sequencing, are sure to reveal new pathways of transformation in the future.

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Primary Mediastinal DLBCL: Evolving Biologic Understanding and Therapeutic Strategies

Cited by 14 publications

References 75 publications

High frequency of CD74 expression in lymphomas: implications for targeted therapy using a novel anti‐CD74‐drug conjugate

High frequency of CD74 expression in lymphomas: implications for targeted therapy using a novel anti‐CD74‐drug conjugate

The treatment of primary mediastinal large B-cell lymphoma: a two decades monocentric experience with 98 patients

The Histological and Biological Spectrum of Diffuse Large B-Cell Lymphoma in the World Health Organization Classification

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