Cancers

Editorial

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Open AccessEditorial

Hodgkin Lymphoma—The Spectrum from Diagnostics to Molecular Science, Movement and Current Treatment Approaches

by Sylvia Hartmann

Cancers 2023, 15(10), 2726; https://doi.org/10.3390/cancers15102726 - 12 May 2023

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Abstract

A total of fourteen papers on Hodgkin lymphoma (HL) are published within this Special Issue, including six reviews, seven original articles and one commentary [...] Full article

(This article belongs to the Special Issue Hodgkin Lymphoma)

Research

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11 pages, 1446 KiB

Open AccessArticle

Outcomes of Patients with Positive Interim Positron Emission Tomography (PET) Continuing ABVD in the Clinical Setting

by Serena Zheng, Kanika Gupta, Piyush Goyal, Reiko Nakajima, Laure Michaud, Connie Lee Batlevi, Paul A. Hamlin, Steven Horwitz, Anita Kumar, Matthew J. Matasar, Alison J. Moskowitz, Craig H. Moskowitz, Ariela Noy, M. Lia Palomba, David J. Straus, Gottfried Von Keudell, Lorenzo Falchi, Joachim Yahalom, Andrew D. Zelenetz, Anas Younes, Gilles Salles, Heiko Schöder and Erel Joffe Show full author list Hide full author list

Cancers 2023, 15(6), 1760; https://doi.org/10.3390/cancers15061760 - 14 Mar 2023

Cited by 6 | Viewed by 1866

Abstract

Recent prospective clinical trial data suggest that patients with Hodgkin’s lymphoma who continue treatment with ABVD, despite failing to attain a complete metabolic response on interim PET (PET2+), may fare better than previously published. We describe the outcomes of PET2+ patients who continued [...] Read more.

Recent prospective clinical trial data suggest that patients with Hodgkin’s lymphoma who continue treatment with ABVD, despite failing to attain a complete metabolic response on interim PET (PET2+), may fare better than previously published. We describe the outcomes of PET2+ patients who continued ABVD and compare the performance of a quantitative measure based on the lesion-to-liver SUV ratio (LLS qPET2+) to that of the subjective Deauville criteria (dvPET2+). We analyzed all patients with newly diagnosed advanced-stage Hodgkin lymphoma treated with frontline ABVD at the Memorial Sloan Kettering Cancer Center between 2008 and 2017. Eligibility was set to correspond with the RATHL inclusion criteria. Images were reviewed by two nuclear medicine physicians and discordant cases were resolved with a third expert in consensus. qPET2+ was defined as LLS ≥ 1.3. We identified 227 patients of whom 25% (57) were qPET2+, but only 14% (31) were dvPET2+. Forty-eight patients (84%) continued ABVD with a 3-year PFS of 70% for qPET2+ and 64% for dvPET2+. In conclusion, interim PET interpretation in clinical practice may be associated with a higher rate of scans deemed positive. Irrespective of the criteria for PET2 positivity, a subset of patients may continue ABVD without a dismal outcome. Full article

(This article belongs to the Special Issue Hodgkin Lymphoma)

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13 pages, 1872 KiB

Open AccessArticle

Histological Subtypes Drive Distinct Prognostic Immune Signatures in Classical Hodgkin Lymphoma

by Claire Lamaison, Juliette Ferrant, Pauline Gravelle, Alexandra Traverse-Glehen, Hervé Ghesquières, Marie Tosolini, Cédric Rossi, Loic Ysebaert, Pierre Brousset, Camille Laurent and Charlotte Syrykh

Cancers 2022, 14(19), 4893; https://doi.org/10.3390/cancers14194893 - 6 Oct 2022

Cited by 3 | Viewed by 1804

Abstract

Despite the success of standard front-line chemotherapy, 20% of classical Hodgkin lymphoma (cHL) patients still relapse or have refractory disease (r/r), and a subset of them die due to disease progression. There is a critical lack of predictive factors for early identification of [...] Read more.

Despite the success of standard front-line chemotherapy, 20% of classical Hodgkin lymphoma (cHL) patients still relapse or have refractory disease (r/r), and a subset of them die due to disease progression. There is a critical lack of predictive factors for early identification of those r/r patients who may benefit from new therapeutic strategies. This study aimed to evaluate the dynamic expression of 586 immune-related genes in a cohort of 42 cHL patients including 30 r/r cHL after first-line chemotherapy. Gene expression profiling (GEP) using NanoString technology identified a 19-gene immune signature at diagnosis predictive of cHL relapse, but dependent on histological subtypes. Genes related to tumor survival were found upregulated while genes related to B-lineage were downregulated at diagnosis in r/r nodular sclerosis cHL. In contrast to the mixed-cellularity subtype, comparative GEP analyses between paired diagnosis/relapse biopsies of nodular sclerosis cHL showed 118 differentially expressed genes, supporting an immune contexture switch at relapse with upregulation of immunosuppressive cytokines, such as LGALS1 and TGFB1, and downregulation of the T-cell co-stimulatory receptor ICOS. These results indicate that the predictive value of immune signature in cHL is strongly influenced by histological subtype which should be considered when assessing new immunotherapy target strategies. Full article

(This article belongs to the Special Issue Hodgkin Lymphoma)

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16 pages, 4497 KiB

Open AccessArticle

Immunosuppressive Microenvironment and Efficacy of PD-1 Inhibitors in Relapsed/Refractory Classic Hodgkin Lymphoma: Checkpoint Molecules Landscape and Macrophage Populations

by Artem Gusak, Liudmila Fedorova, Kirill Lepik, Nikita Volkov, Marina Popova, Ivan Moiseev, Natalia Mikhailova, Vadim Baykov and Alexander Kulagin

Cancers 2021, 13(22), 5676; https://doi.org/10.3390/cancers13225676 - 12 Nov 2021

Cited by 20 | Viewed by 3196

Abstract

To date, the impact of the tumor microenvironment on the prognosis of patients with classic Hodgkin lymphoma (cHL) during anti-PD-1 therapy has been studied insufficiently. This retrospective study included 61 primary samples of lymph nodes from patients who had relapsed/refractory (r/r) cHL and [...] Read more.

To date, the impact of the tumor microenvironment on the prognosis of patients with classic Hodgkin lymphoma (cHL) during anti-PD-1 therapy has been studied insufficiently. This retrospective study included 61 primary samples of lymph nodes from patients who had relapsed/refractory (r/r) cHL and were treated with nivolumab. Repeated samples were obtained in 15 patients at relapse or disease progression after immunotherapy. Median follow-up was 55 (13–63) months. The best overall response rate and progression-free survival (PFS) were analyzed depending on the expression of CD68, CD163, PD-1, LAG-3, TIM-3, CTLA-4, TIGIT, CD163/c-maf in the tumor microenvironment in primary and sequential biopsies. The combination of CD163/c-maf antibodies was used for the identification of M2 macrophages (M2). A low number of macrophages in primary samples was associated with inferior PFS during nivolumab treatment (for CD163-positive cells p = 0.0086; for CD68-positive cells p = 0.037), while a low number of M2 with higher PFS (p = 0.014). Complete response was associated with a lower level of M2 (p = 0.011). In sequential samples (before and after nivolumab therapy) an increase in PD-1 (p = 0.011) and LAG-3 (p = 0.0045) and a depletion of CD68 (p = 0.057) and CD163 (p = 0.0049)-positive cells were observed. The study expands understanding of the cHL microenvironment structure and dynamics during nivolumab therapy in patients with r/r cHL. Full article

(This article belongs to the Special Issue Hodgkin Lymphoma)

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14 pages, 2434 KiB

Open AccessArticle

Landscape of 4D Cell Interaction in Hodgkin and Non-Hodgkin Lymphomas

by Sylvia Hartmann, Sonja Scharf, Yvonne Steiner, Andreas G. Loth, Emmanuel Donnadieu, Nadine Flinner, Viola Poeschel, Stephanie Angel, Moritz Bewarder, Julia Bein, Uta Brunnberg, Alessandro Bozzato, Bernhard Schick, Stephan Stilgenbauer, Rainer M. Bohle, Lorenz Thurner and Martin-Leo Hansmann

Cancers 2021, 13(20), 5208; https://doi.org/10.3390/cancers13205208 - 17 Oct 2021

Cited by 11 | Viewed by 2469

Abstract

Profound knowledge exists about the clinical, morphologic, genomic, and transcriptomic characteristics of most lymphoma entities. However, information is currently lacking on the dynamic behavior of malignant lymphomas. This pilot study aimed to gain insight into the motility of malignant lymphomas and bystander cells [...] Read more.

Profound knowledge exists about the clinical, morphologic, genomic, and transcriptomic characteristics of most lymphoma entities. However, information is currently lacking on the dynamic behavior of malignant lymphomas. This pilot study aimed to gain insight into the motility of malignant lymphomas and bystander cells in 20 human lymph nodes. Generally, B cells were faster under reactive conditions compared with B cells in malignant lymphomas. In contrast, PD1-positive T cells did not show systematic differences in velocity between reactive and neoplastic conditions in general. However, lymphomas could be divided into two groups: one with fast PD1-positive T cells (e.g., Hodgkin lymphoma and mantle cell lymphoma; means 8.4 and 7.8 µm/min) and another with slower PD1-positive T cells (e.g., mediastinal grey zone lymphoma; mean 3.5 µm/min). Although the number of contacts between lymphoma cells and PD1-positive T cells was similar in different lymphoma types, important differences were observed in the duration of these contacts. Among the lymphomas with fast PD1-positive T cells, contacts were particularly short in mantle cell lymphoma (mean 54 s), whereas nodular lymphocyte-predominant Hodgkin lymphoma presented prolonged contact times (mean 6.1 min). Short contact times in mantle cell lymphoma were associated with the largest spatial displacement of PD1-positive cells (mean 12.3 µm). Although PD1-positive T cells in nodular lymphocyte-predominant Hodgkin lymphoma were fast, they remained in close contact with the lymphoma cells, in line with a dynamic immunological synapse. This pilot study shows for the first time systematic differences in the dynamic behavior of lymphoma and bystander cells between different lymphoma types. Full article

(This article belongs to the Special Issue Hodgkin Lymphoma)

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15 pages, 2063 KiB

Open AccessArticle

Deregulated miRNAs Contribute to Silencing of B-Cell Specific Transcription Factors and Activation of NF-κB in Classical Hodgkin Lymphoma

by Julia Paczkowska, Joanna Janiszewska, Adam Ustaszewski, Julia Bein, Marcin Skalski, Agnieszka Dzikiewicz-Krawczyk, Natalia Rozwadowska, Martin-Leo Hansmann, Sylvia Hartmann and Maciej Giefing

Cancers 2021, 13(13), 3131; https://doi.org/10.3390/cancers13133131 - 23 Jun 2021

Cited by 5 | Viewed by 2866

Abstract

A hallmark of classical Hodgkin lymphoma (cHL) is the attenuation of B-cell transcription factors leading to global transcriptional reprogramming. The role of miRNAs (microRNAs) involved in this process is poorly studied. Therefore, we performed global miRNA expression profiling using RNA-seq on commonly used [...] Read more.

A hallmark of classical Hodgkin lymphoma (cHL) is the attenuation of B-cell transcription factors leading to global transcriptional reprogramming. The role of miRNAs (microRNAs) involved in this process is poorly studied. Therefore, we performed global miRNA expression profiling using RNA-seq on commonly used cHL cell lines, non-Hodgkin lymphoma cell lines and sorted normal CD77⁺ germinal centre B-cells as controls and characterized the cHL miRNome (microRNome). Among the 298 miRNAs expressed in cHL, 56 were significantly overexpressed and 23 downregulated (p < 0.05) compared to the controls. Moreover, we identified five miRNAs (hsa-miR-9-5p, hsa-miR-24-3p, hsa-miR-196a-5p, hsa-miR-21-5p, hsa-miR-155-5p) as especially important in the pathogenesis of this lymphoma. Target genes of the overexpressed miRNAs in cHL were significantly enriched (p < 0.05) in gene ontologies related to transcription factor activity. Therefore, we further focused on selected interactions with the SPI1 and ELF1 transcription factors attenuated in cHL and the NF-ĸB inhibitor TNFAIP3. We confirmed the interactions between hsa-miR-27a-5p:SPI1, hsa-miR-330-3p:ELF-1, hsa-miR-450b-5p:ELF-1 and hsa-miR-23a-3p:TNFAIP3, which suggest that overexpression of these miRNAs contributes to silencing of the respective genes. Moreover, by analyzing microdissected HRS cells, we demonstrated that these miRNAs are also overexpressed in primary tumor cells. Therefore, these miRNAs play a role in silencing the B-cell phenotype in cHL. Full article

(This article belongs to the Special Issue Hodgkin Lymphoma)

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13 pages, 1141 KiB

Open AccessArticle

Interaction between ERAP Alleles and HLA Class I Types Support a Role of Antigen Presentation in Hodgkin Lymphoma Development

by Peijia Jiang, Rianne N. Veenstra, Annika Seitz, Ilja M. Nolte, Bouke G. Hepkema, Lydia Visser, Anke van den Berg and Arjan Diepstra

Cancers 2021, 13(3), 414; https://doi.org/10.3390/cancers13030414 - 22 Jan 2021

Cited by 8 | Viewed by 2806

Abstract

Genetic variants in the HLA region are the strongest risk factors for developing Hodgkin lymphoma (HL), suggesting an important role for antigen presentation. This is supported by another HL-associated genomic region which contains the loci of two enzymes that process endogenous proteins to [...] Read more.

Genetic variants in the HLA region are the strongest risk factors for developing Hodgkin lymphoma (HL), suggesting an important role for antigen presentation. This is supported by another HL-associated genomic region which contains the loci of two enzymes that process endogenous proteins to peptides to be presented by HLA class I, i.e., endoplasmic reticulum aminopeptidase 1 (ERAP1) and ERAP2. We hypothesized that ERAP and HLA class I type interact in HL susceptibility, as shown previously for several autoimmune diseases. We detected ERAP1 and ERAP2 expression in tumor cells and cells in the microenvironment in primary HL tissue samples. Seven ERAP SNPs and ERAP1 haplotypes showed strong associations with RNA and protein levels of ERAP1 and ERAP2 in LCLs and HL cell lines. Analysis of HLA class I types, ERAP SNPs and ERAP haplotypes by direct genotyping or imputation from genome-wide association data in 390 HL patients revealed significant interactions between HLA-A11, rs27038 and the rs27038 associated ERAP haplotype, as well as between HLA-Cw2 and rs26618. In conclusion, our results show that ERAP and HLA class I interact in genetic susceptibility to HL, providing further evidence that antigen presentation is an important process in HL susceptibility and pathogenesis. Full article

(This article belongs to the Special Issue Hodgkin Lymphoma)

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13 pages, 413 KiB

Open AccessArticle

Defining the Inflammatory Plasma Proteome in Pediatric Hodgkin Lymphoma

by Jennifer E. Agrusa, Brooks P. Scull, Harshal A. Abhyankar, Howard Lin, Nmazuo W. Ozuah, Rikhia Chakraborty, Olive S. Eckstein, Nitya Gulati, Elmoataz Abdel Fattah, Nader K. El-Mallawany, Rayne H. Rouce, ZoAnn E. Dreyer, Julienne Brackett, Judith F. Margolin, Joseph Lubega, Terzah M. Horton, Catherine M. Bollard, M. Monica Gramatges, Kala Y. Kamdar, Kenneth L. McClain, Tsz-Kwong Man and Carl E. Allen Show full author list Hide full author list

Cancers 2020, 12(12), 3603; https://doi.org/10.3390/cancers12123603 - 2 Dec 2020

Cited by 7 | Viewed by 2703

Abstract

Hodgkin lymphoma (HL) histopathology is characterized by rare malignant Reed–Sternberg cells among an inflammatory infiltrate. We hypothesized that characteristics of inflammation in pediatric HL lesions would be reflected by the levels of inflammatory cytokines or chemokines in pre-therapy plasma of children with HL. [...] Read more.

Hodgkin lymphoma (HL) histopathology is characterized by rare malignant Reed–Sternberg cells among an inflammatory infiltrate. We hypothesized that characteristics of inflammation in pediatric HL lesions would be reflected by the levels of inflammatory cytokines or chemokines in pre-therapy plasma of children with HL. The study objectives were to better define the inflammatory pre-therapy plasma proteome and identify plasma biomarkers associated with extent of disease and clinical outcomes in pediatric HL. Pre-therapy plasma samples were obtained from pediatric subjects with newly diagnosed HL and healthy pediatric controls. Plasma concentrations of 135 cytokines/chemokines were measured with the Luminex platform. Associations between protein concentration and disease characteristics were determined using multivariate permutation tests with false discovery control. Fifty-six subjects with HL (mean age: 13 years, range 3–18) and 47 controls were analyzed. The cytokine/chemokine profiles of subjects with HL were distinct from controls, and unique cytokines/chemokines were associated with high-risk disease (IL-10, TNF-α, IFN-γ, IL-8) and slow early response (CCL13, IFN-λ1, IL-8). TNFSF10 was significantly elevated among those who ultimately relapsed and was significantly associated with worse event-free survival. These biomarkers could be incorporated into biologically based risk stratification to optimize outcomes and minimize toxicities in pediatric HL. Full article

(This article belongs to the Special Issue Hodgkin Lymphoma)

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Review

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14 pages, 553 KiB

Open AccessReview

Minimising the Toxicities of First Line Hodgkin Lymphoma Treatment in the Modern Era

by Annabel M. Follows and Anna Santarsieri

Cancers 2022, 14(21), 5390; https://doi.org/10.3390/cancers14215390 - 1 Nov 2022

Cited by 5 | Viewed by 2641

Abstract

Striking advances in the treatment of Hodgkin lymphoma over the last 30 years have culminated in high rates of disease-free survival in younger patients with early and advanced stage disease. In this review we focus on strategies that have evolved over recent years [...] Read more.

Striking advances in the treatment of Hodgkin lymphoma over the last 30 years have culminated in high rates of disease-free survival in younger patients with early and advanced stage disease. In this review we focus on strategies that have evolved over recent years to reduce short and long-term toxicities of treatment. These strategies include the selection of first-line chemotherapy, the stratification of patients based on initial response and subsequent adaptation of treatment, the addition of novel agents (e.g., brentuximab vedotin), the removal of specific drugs (e.g., bleomycin), the use of drug substitution, and the removal of consolidation radiotherapy based on interim and end of treatment PET assessment. While these strategies have successfully reduced toxicity of Hodgkin lymphoma therapy, the cornerstone of treatment continues to be combination chemotherapy and radiotherapy with significant short- and long-term side effects. To further reduce toxicity while maintaining or improving efficacy, we shall need to incorporate novel agents into our first-line treatment algorithms, and several such potentially practice-changing trials are underway. Full article

(This article belongs to the Special Issue Hodgkin Lymphoma)

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21 pages, 3394 KiB

Open AccessReview

The Grey Zones of Classic Hodgkin Lymphoma

by Jan Bosch-Schips, Massimo Granai, Leticia Quintanilla-Martinez and Falko Fend

Cancers 2022, 14(3), 742; https://doi.org/10.3390/cancers14030742 - 31 Jan 2022

Cited by 14 | Viewed by 6294

Abstract

Classic Hodgkin lymphoma (CHL) is a well-defined neoplasm characterized by the presence of a minority of pathognomonic Hodgkin and Reed–Sternberg (HRS) cells in a reactive inflammatory background. Although genotypically of B cell origin, HRS cells exhibit a downregulated B cell program and therefore [...] Read more.

Classic Hodgkin lymphoma (CHL) is a well-defined neoplasm characterized by the presence of a minority of pathognomonic Hodgkin and Reed–Sternberg (HRS) cells in a reactive inflammatory background. Although genotypically of B cell origin, HRS cells exhibit a downregulated B cell program and therefore are set apart from other B cell lymphomas in the current WHO classification. However, cases with morphological and phenotypic features overlapping with CHL have been recognized, and the category of B cell lymphoma—unclassifiable—with features intermediate between diffuse large B cell lymphoma (DLBCL) and CHL, also termed grey zone lymphoma, was first introduced into the WHO classification in 2008 as provisional entity. These cases, as well as others raising a differential diagnosis of CHL can present diagnostic problems, as well as therapeutic challenges. Whereas some of these lymphomas only represent biologically unrelated morphological mimics, others, especially mediastinal grey zone lymphoma, exhibit genetic and gene expression profiles which overlap with CHL, indicating a true biological relationship. In this review, we address areas of diagnostic difficulties between CHL and other lymphoma subtypes, discuss the biological basis of true grey zone lymphoma based on recent molecular studies and delineate current concepts for the classification of these rare tumors. Full article

(This article belongs to the Special Issue Hodgkin Lymphoma)

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15 pages, 1498 KiB

Open AccessReview

Hodgkin Lymphoma in People Living with HIV

by Jose-Tomas Navarro, José Moltó, Gustavo Tapia and Josep-Maria Ribera

Cancers 2021, 13(17), 4366; https://doi.org/10.3390/cancers13174366 - 29 Aug 2021

Cited by 17 | Viewed by 4283

Abstract

Despite widespread use of combined antiretroviral therapy (cART) and increased life expectancy in people living with HIV (PLWH), HIV-related lymphomas (HRL) remain a leading cause of cancer morbidity and mortality for PLWH, even in patients optimally treated with cART. While the incidence of [...] Read more.

Despite widespread use of combined antiretroviral therapy (cART) and increased life expectancy in people living with HIV (PLWH), HIV-related lymphomas (HRL) remain a leading cause of cancer morbidity and mortality for PLWH, even in patients optimally treated with cART. While the incidence of aggressive forms of non-Hodgkin lymphoma decreased after the advent of cART, incidence of Hodgkin lymphoma (HL) has increased among PLWH in recent decades. The coinfection of Epstein–Barr virus plays a crucial role in the pathogenesis of HL in the HIV setting. Currently, PLWH with HRL, including HL, are treated similarly to HIV-negative patients and, importantly, the prognosis of HL in PLWH is approaching that of the general population. In this regard, effective cART during chemotherapy is strongly recommended since it has been shown to improve survival rates in all lymphoma subtypes, including HL. As a consequence, interdisciplinary collaboration between HIV specialists and hemato-oncologists for the management of potential drug–drug interactions and overlapping toxicities between antiretroviral and antineoplastic drugs is crucial for the optimal treatment of PLWH with HL. In this article the authors review and update the epidemiological, clinical and biological aspects of HL presenting in PLWH with special emphasis on advances in prognosis and the factors that have contributed to it. Full article

(This article belongs to the Special Issue Hodgkin Lymphoma)

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14 pages, 2691 KiB

Open AccessReview

FDG-PET/CT for the Management of Post-Chemotherapy Residual Mass in Hodgkin lymphoma

by Andrea Gallamini, Michał Kurlapski and Jan Maciej Zaucha

Cancers 2021, 13(16), 3952; https://doi.org/10.3390/cancers13163952 - 5 Aug 2021

Cited by 6 | Viewed by 4616

Abstract

In the present review, the authors report the published evidence on the use of functional imaging with FDG-PET/CT in assessing the final response to treatment in Hodgkin lymphoma. Despite a very high overall Negative Predictive Value of post-chemotherapy PET on treatment outcome ranging [...] Read more.

In the present review, the authors report the published evidence on the use of functional imaging with FDG-PET/CT in assessing the final response to treatment in Hodgkin lymphoma. Despite a very high overall Negative Predictive Value of post-chemotherapy PET on treatment outcome ranging from 94% to 86%, according to different treatment intensity, the Positive Predicting Value proved much lower (40–25%). In the present review the Authors discuss the role of PET to guide consolidation RT over a RM after different chemotherapy regimens, both in early and in advanced-stage disease. A particular emphasis is dedicated to the peculiar issue of the qualitative versus semi-quantitative methods for End-of Therapy PET scan interpretation. A short hint will be given on the role of FDG-PET to assess the treatment outcome after immune checkpoint inhibitors. Full article

(This article belongs to the Special Issue Hodgkin Lymphoma)

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11 pages, 712 KiB

Open AccessReview

Review of Treatment Options for the Management of Advanced Stage Hodgkin Lymphoma

by Hélène Vellemans and Marc P. E. André

Cancers 2021, 13(15), 3745; https://doi.org/10.3390/cancers13153745 - 26 Jul 2021

Cited by 8 | Viewed by 3293

Abstract

Hodgkin lymphoma (HL) is a lymphoid-type hematologic disease that is derived from B cells. The incidence of this lymphoid malignancy is around 2–3/100,000/year in the western world. Long-term remission rates are linked to a risk-adapted approach, which allows remission rates higher than 80%. [...] Read more.

Hodgkin lymphoma (HL) is a lymphoid-type hematologic disease that is derived from B cells. The incidence of this lymphoid malignancy is around 2–3/100,000/year in the western world. Long-term remission rates are linked to a risk-adapted approach, which allows remission rates higher than 80%. The first-line treatment for advanced stage classical HL (cHL) widely used today is doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP_esc) chemotherapy. Randomized studies comparing these two regimens and a recently performed meta-analysis have demonstrated consistently better disease control with BEACOPP_esc. However, this treatment is not the standard of care, as there is an excess of acute hematological toxicities and therapy-related myeloid neoplasms. Moreover, there is a recurrent controversy concerning the impact on overall survival with this regimen. More recently, new drugs such as brentuximab vedotin and checkpoint inhibitors have become available and have been evaluated in combination with doxorubicin, vinblastine, and dacarbazine (AVD) for the first-line treatment of patients with advanced cHL with the objective of tumor control improvement. There are still major debates with respect to first-line treatment of advanced cHL. The use of positron emission tomography-adapted strategies has allowed a reduction in the toxicity of chemotherapy regimens. Incorporation of new drugs into the treatment algorithms requires confirmation. Full article

(This article belongs to the Special Issue Hodgkin Lymphoma)

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17 pages, 5219 KiB

Open AccessFeature PaperReview

Pitfalls in the Diagnosis of Nodular Lymphocyte Predominant Hodgkin Lymphoma: Variant Patterns, Borderlines and Mimics

by Sheren Younes, Rebecca B. Rojansky, Joshua R. Menke, Dita Gratzinger and Yasodha Natkunam

Cancers 2021, 13(12), 3021; https://doi.org/10.3390/cancers13123021 - 16 Jun 2021

Cited by 25 | Viewed by 14617

Abstract

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) represents approximately 5% of Hodgkin lymphoma and typically affects children and young adults. Although the overall prognosis is favorable, variant growth patterns in NLPHL correlate with disease recurrence and progression to T-cell/histiocyte-rich large B-cell lymphoma or frank [...] Read more.

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) represents approximately 5% of Hodgkin lymphoma and typically affects children and young adults. Although the overall prognosis is favorable, variant growth patterns in NLPHL correlate with disease recurrence and progression to T-cell/histiocyte-rich large B-cell lymphoma or frank diffuse large B-cell lymphoma (DLBCL). The diagnostic boundary between NLPHL and DLBCL can be difficult to discern, especially in the presence of variant histologies. Both diagnoses are established using morphology and immunophenotype and share similarities, including the infrequent large tumor B-cells and the lymphocyte and histiocyte-rich microenvironment. NLPHL also shows overlap with other lymphomas, particularly, classic Hodgkin lymphoma and T-cell lymphomas. Similarly, there is overlap with non-neoplastic conditions, such as the progressive transformation of germinal centers. Given the significant clinical differences among these entities, it is imperative that NLPHL and its variants are carefully separated from other lymphomas and their mimics. In this article, the characteristic features of NLPHL and its diagnostic boundaries and pitfalls are discussed. The current understanding of genetic features and immune microenvironment will be addressed, such that a framework to better understand biological behavior and customize patient care is provided. Full article

(This article belongs to the Special Issue Hodgkin Lymphoma)

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Other

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8 pages, 251 KiB

Open AccessCommentary

Pegfilgrastim in Supportive Care of Hodgkin Lymphoma

by Claudio Cerchione, Davide Nappi, Alessandra Romano and Giovanni Martinelli

Cancers 2022, 14(17), 4063; https://doi.org/10.3390/cancers14174063 - 23 Aug 2022

Cited by 1 | Viewed by 1867

Abstract

Neutropenia and febrile neutropenia are common and potentially life-threating events associated with chemotherapy treatment in Hodgkin lymphoma (HL). Neutropenia-related infectious events could be an issue both for direct clinical consequences and for delay in treatment delivery, affecting final outcomes in a potentially highly [...] Read more.

Neutropenia and febrile neutropenia are common and potentially life-threating events associated with chemotherapy treatment in Hodgkin lymphoma (HL). Neutropenia-related infectious events could be an issue both for direct clinical consequences and for delay in treatment delivery, affecting final outcomes in a potentially highly curable disease. Pegfilgrastim is the pegylated form of filgrastim, the recombinant form of human G-CSF, capable of prevent and mitigate neutropenic effects of chemotherapy, when adopted as primary prophylaxis in several hematological malignancies. No updated version of major international guidelines provides clear indication on prophylaxis use of pegfilgrastim in HL to prevent febrile neutropenia episodes in HL. Moreover, to date, scarce and non-uniform clinical experiences evaluating pegfilgrastim as prophylaxis in HL are present in the literature. Herein, we propose a brief summary of the literature data about efficacy and safety of the use of pegfilgrastim as primary prophylaxis in HL during chemotherapy treatment. Full article

(This article belongs to the Special Issue Hodgkin Lymphoma)

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