Hodgkin’s Lymphoma: Biology and Treatment Strategies for Primary, Refractory, and Relapsed Disease

Diehl, Volker; Stein, Harald; Hummel, Michael; Zollinger, Raphaël; Connors, Joseph M.

doi:10.1182/asheducation-2003.1.225

Cited by 145 publications

(98 citation statements)

References 115 publications

(34 reference statements)

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“…3 Hodgkin's lymphoma is a curable neoplasm given that, after a minimum follow-up of 6 years, more than 90% of patients are still alive and 80% are considered cured. 4 These rewarding results have been obtained by a combination of factors influencing treatment outcome in different ways. These factors can be briefly summarized as: (i) increasing accuracy of staging procedures; (ii) different treatment strategies tailored to well-defined categories of patients with different risks of treatment failure; (iii) the peculiar neoplastic tissue architecture in Hodgkin's lymphoma, which differs from that in more common subtypes of lymphoma such as diffuse large B-cell lymphoma and follicular lymphoma; and (iv) the marked chemosensitivity and radiosensitivity of the tumor.…”

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confidence: 99%

Positron emission tomography scanning: a new paradigm for the management of Hodgkin's lymphoma

Gallamini¹

2010

Haematologica

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T he findings of positron emission tomography (PET), performed very early during ABVD chemotherapy have been proven to be the most important prognostic information for predicting treatment outcome in patients with Hodgkin's lymphoma treated with this chemotherapeutic regimen. 1,2 However, many issues remain controversial, and shared, standard criteria for interpreting PET findings have not yet been determined. It is still unclear, for instance, whether a qualitative approach based on visual assessment should be used, or whether a semi-quantitative approach involving standardized uptake value (SUV) analysis of 2-[ 18 F]fluoro-2-deoxyglucose (FDG) is preferred for PET reporting. In this issue of the Journal, Dann et al. propose a new scoring system for the interpretation of interim PET scans in patients with Hodgkin's lymphoma treated with either ABVD or BEA-COPP chemotherapy. 3 Hodgkin's lymphoma is a curable neoplasm given that, after a minimum follow-up of 6 years, more than 90% of patients are still alive and 80% are considered cured. 4 These rewarding results have been obtained by a combination of factors influencing treatment outcome in different ways. These factors can be briefly summarized as: (i) increasing accuracy of staging procedures; (ii) different treatment strategies tailored to well-defined categories of patients with different risks of treatment failure; (iii) the peculiar neoplastic tissue architecture in Hodgkin's lymphoma, which differs from that in more common subtypes of lymphoma such as diffuse large B-cell lymphoma and follicular lymphoma; and (iv) the marked chemosensitivity and radiosensitivity of the tumor. It can be hypothesized that there is a close relationship between the last two factors: indeed, the tumor tissue in Hodgkin's lymphoma is composed of a few, scattered neoplastic cells called Hodgkin and Reed-Sternberg (HRS) cells, accounting for less than 1% of the total cell count found in biopsy specimens, surrounded by a overwhelming population of non-neoplastic mononuclear bystander cells. 5 These latter cells are recruited by chemokines produced by the HRS cells and induce expression of anti-apoptotic proteins in HRS cells and their immortalization via a paracrine loop. 6 The chemokines responsible for recruitment of cells to the microenvironment, thymus and activation-regulated chemokines (TARC-CCL7) and macrophage-derived chemokines (MDC), selectively attract CCR4-expressing cell subsets, including eosinophils, histiocytes, macrophages, plasma cells, and Th2 and Treg lymphocytes, which are all readily detected at tumor sites. There is convincing evidence that forced expression of CCR4 by these various subsets of cells provides the cells with the capacity to migrate along a TARC gradient, so that the function of the CCR4 receptor is not restricted to the subset of T cells on which it is physiologically expressed. 7 These cells are metabolically very active, produce chemokines to recruit new accessory cells and block apoptosis of the HRS. 8 The role of macrophages in recruiting ...

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confidence: 99%

Positron emission tomography scanning: a new paradigm for the management of Hodgkin's lymphoma

Gallamini¹

2010

Haematologica

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“…Before 1990, Bower et al reported an incidence of PML among patients with LPDs of 0.52% (5 cases in treatment in the 1990s has brought a dramatic reduction in failure and subsequent progression of disease [53]. Another explanation could be that the association between Hodgkin disease and PML is already well known and therefore not worth reporting.…”

Section: Discussionmentioning

confidence: 99%

Changes in the natural history of progressive multifocal leukoencephalopathy in HIV-negative lymphoproliferative disorders: Impact of novel therapies

et al. 2005

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The aims of this study were to evaluate the clinical characteristics of HIV-negative patients affected by lymphoproliferative disorders (LPD) who developed progressive multifocal leukoencephalopathy (PML), to delineate the risk factors, and to analyze whether the new antineoplastic therapies are changing the natural history of this infectious disease. We retrospectively analyzed 46 cases with confirmed LPD-associated PML published from 1958 to 2004. Patients were stratified according to two different time periods: group A included patients diagnosed before 1989, and group B included patients diagnosed since 1990, after introduction of purine analogues. Group A patients (n = 22) had received alkylating agents and/or radiotherapy, and the majority (63.6%) had advanced Hodgkin disease. At univariate analysis, uncontrolled Hodgkin disease was the only risk factor for PML. In group B patients (n = 24), the most frequent treatments received were purine analogues (58.3%) and high-dose therapy with hematopoietic stem cell transplantation (33.3%; HDT/HSCT). B-cell chronic lymphocytic leukemia (45.8%) and aggressive non-Hodgkin lymphoma (24.9%) were the most frequent underlying LPDs. Patients treated with purine analogues were more likely to have active LPD, lower CD4 cell counts, and to be older and male than were HSCT recipients. The median interval from purine analogues or HDT/HSCT to PML was 11 months. In HDT/HSCT recipients, this interval was delayed for 10 months when peri-transplantation rituximab was used. Univariate analysis identified age >55 years, male sex, and CD4 cell counts £0.2 · 10 9 /L as risk factors for PML in patients treated with purine analogues. Mortality rates were 95.4% (group A patients), 90% (purine analogues), and 62.5% (HDT/HSCT recipients). At univariate analysis, the only factor that significantly correlated with recovery from infection was female sex. Our findings indicate (1) the possible reduction in reported cases associated with Hodgkin disease and the increasing number of published cases associated with the new antineoplastic therapies (purine analogues and HDT/ HSCT); (2) among patients treated with purine analogues, PML is more common in male patients with CD4 cell counts £0.2 · 10 9 /L; (3) the use of rituximab after HDT/ HSCT seems to delay the onset of PML; and (4) the prognosis is slightly better in transplant recipients. Am.

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“…Currently, treatment options of HL are tailored to type, stage, patient age, and an assessment of the risk of resistance (Diehl et al, 2003;Klimm et al, 2005). The induction chemotherapy regimens given as the initial treatment for HL are shown in Table 3.…”

Section: Chemotherapy For Early-stage Chlmentioning

confidence: 99%

Epstein-Barr Virus-Associated Classical Hodgkin Lymphoma and Its Therapeutic Strategies

Lee¹

2011

Biomolecules and Therapeutics

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Lymphoma is a type of cancer involving cells of the immune system, and has two major categories: Hodgkin lymphoma (HL) and all other lymphomas (non-HL). Although the two types may display the same symptoms, they are readily distinguishable via microscopic examination, and differ in the way they develop, spread and are treated. HL is a unique clinicopathological disorder characterized by the rare presence of malignant cells (usually accounting for 0.1% to 10% of the cells in the total tumor mass) in a background of a nonneoplastic cellular microenvironment comprising T-and Blymphocytes and other cell types (Weiss et al., 1999). In the United States, about 8,500 new cases of HL were expected to be diagnosed in 2010, and the overall incidence is increasing each year (Maggioncalda et al., 2011).Although the pathogenesis of HL is still largely unknown, the association of HL with Epstein-Barr virus (EBV) infection has been demonstrated in many reports. For examples, HL patients show elevated antibody titers to EBV antigens (Levine et al., 1971), and the risk of developing HL is increased up to three-fold in population that have experienced infectious mononucleosis caused by primary EBV infection (Gutensohn Over the past few decades, our understanding of the epidemiology and immunopathogenesis of Hodgkin lymphoma (HL) has made enormous advances. Consequently, the treatment of HL has changed signifi cantly, rendering this disease of the most curable human cancers. To date, about 80% of patients achieve long-term disease-free survival. However, therapeutic challenges still remain, particularly regarding the salvage strategies for relapsed and refractory disease, which need further identifi cation of better prognostic markers and novel therapeutic schemes. Although the precise molecular mechanism by which Epstein-Barr virus (EBV) contributes to the generation of malignant cells present in HL still remains unknown, current increasing data on the role of EBV in the pathobiology of HL have encouraged people to start developing novel and specifi c therapeutic strategies for EBVassociated HL. This review will provide an overview of therapeutic approaches for acute EBV infection and the classical form of HL (cHL), especially focusing on EBV-associated HL cases. and Cole, 1980), and EBV DNA/RNA can be detected in HL tissues (Brink et al., 1997), suggesting that as a primary event in the development of this disease, EBV infection may play a very crucial role in the pathogenesis of HL. AbstractAccording to a population-based cohort study, the frequency of EBV associated HL among total HL cases varies from 30 to 50% (in certain cases even higher; >90% in developing and underdeveloped countries, and >95% in HIV associated cases), and most of them appear in classical Hodgkin lymphoma (cHL), the major type of HL (Herbst et al., 1991;Pallesen et al., 1991;Ambinder et al., 1993;Leoncini et al., 1996). Since EBV is an oncogenic virus that is able to subvert cellular processes supporting growth and survival, the approach to unravel the f...

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Hodgkin’s Lymphoma: Biology and Treatment Strategies for Primary, Refractory, and Relapsed Disease

Cited by 145 publications

References 115 publications

Positron emission tomography scanning: a new paradigm for the management of Hodgkin's lymphoma

Positron emission tomography scanning: a new paradigm for the management of Hodgkin's lymphoma

Changes in the natural history of progressive multifocal leukoencephalopathy in HIV-negative lymphoproliferative disorders: Impact of novel therapies

Epstein-Barr Virus-Associated Classical Hodgkin Lymphoma and Its Therapeutic Strategies

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