Part II: Hodgkin's lymphoma—diagnosis and treatment

doi:10.1016/S1470-2045(03)01320-2

The Lancet Oncology

Volume 5, Issue 1, January 2004, Pages 19-26

https://doi.org/10.1016/S1470-2045(03)01320-2 Get rights and content

Summary

The outcome of patients with all stages of Hodgkin's lymphoma has improved dramatically over the past few decades. This is mainly due to the use of risk-adapted therapies using intensive polychemotherapeutic regimens in combination with other modalities. Patients with early favourable or unfavourable (intermediate) stage disease receive two or four cycles of chemotherapy, respectively, followed by involved-field radiotherapy (20–30 Gy). Advanced stage Hodgkin's lymphoma is treated more aggressively using six to eight cycles of chemotherapy but the effectiveness of consolidative radiotherapy for patients who show a complete response after chemotherapy alone is still unknown. The main challenge in the near future will be the development of strategies that decrease late morbidity and mortality but retain the same efficacy of current regi- mens. In this paper we review current diagnostic techniques and management strategies used to treat Hodgkin's lymphoma, and the range of new modalities being used to improve long-term outcome and patient quality of life.

Section snippets

Diagnosis and staging

An excisional biopsy of a suspicious lymph node should be done for the initial diagnosis of Hodgkin's lymphoma. The extent of disease is assessed with the four-stage Cotswolds modification of the Ann Arbor classification.¹ Information about prognostic factors such as mediastinal mass, other bulky nodal disease, and the extent of subdiaphragmatic disease is included in this classification (table 1).

Two-thirds of patients with newly diagnosed Hodgkin's lymphoma have radiographical evidence of

Prognostic factors and treatment groups

Despite an enormous effort to define clinically relevant and generally acceptable prognostic factors, stage and systemic B-cell symptoms are still the two major determinants for stratifying patients with Hodgkin's lymphoma. Bulky disease (>10 cm) has recently emerged as a third prognostic factor that meets general acceptance. In the USA, most centres treat patients accord- ing to the traditional classifications of early stages (I–IIA or B) and advanced stages (III–IVA or B; I–IIB with bulky

Early-stage favourable disease

Until recently, early-stage favourable Hodgkin's lymphoma was treated with extended-field irradiation without chemotherapy. However, due to the high incidence of relapse (about 25–30%) and fatal long-term effects (secondary neoplasms or cardiac toxicity), extended-field radiotherapy is now being abandoned by most study groups in favour of combined therapy6, 7 consisting of a short-dura- tion chemotherapy (eg, two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine; ABVD) and

The pioneers: MOPP and ABVD

A few decades ago, patients with advanced stages of Hodgkin's lymphoma were incurable. De Vita and colleagues at the National Cancer Institute achieved a 50% cure rate in patients with advanced-stage disease with a drug combination called MOPP (mechlorethamine, vincristine, procarbazine, and prednisone).9, 10, 11 The same regimen with chlorambucil or cyclophosphamide in place of mechlorethamine showed similar efficacy and was associated with less acute toxicity. The British National Lymphoma

Conclusion

The rationale behind treatment of patients with Hodgkin's lymphoma is to classify patients as having early favourable, unfavourable (intermediate), or advanced-stage disease according to anatomic stage and B-symptoms (and possibly prognostic factors, such as the IPS). Patients with early favourable disease should be treated with a moderate chemotherapy (typically two to four cycles of ABVD) and involved-field radiation (20–30 Gy). Patients with early unfavourable disease should receive four

Search strategy and selection criteria

We identified relevant articles with searches of PubMed with the terms “Hodgkin's disease”, “Hodgkin's lymphoma”, “chemotherapy”, “radiotherapy”, “prognostic factors”. References from relevant articles were also included. Additional papers were selected from the authors personal collections.

Conflicts of interest

None declared.

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Cited by (152)

PET/CT in Hodgkin Lymphoma: An Update
2023, Seminars in Nuclear Medicine
¹⁸F-FDG-PET/CT is now an integral part of the workup and management of patients with Hodgkin's lymphoma (HL). PET/CT is currently routinely performed for staging and for response assessment at the end of treatment. Interim PET/CT is typically performed after 1-4 of 6-8 chemo/chemoimmunotherapy cycles ± radiation for prognostication and potential treatment escalation or de-escalation early in the course of therapy, a concept known as response-or risk-adapted treatment. Quantitative PET is an area of growing interest. Metrics such as the standardized uptake value (SUV), metabolic tumor volume, total lesion glycolysis, and their changes with treatment are being investigated as more reproducible and, potentially, more accurate predictors of response and prognosis. Despite the progress made in standardizing the use of PET/CT in lymphoma, challenges remain, particularly with respect to its limited positive predictive value. This review highlights the most relevant applications of PET/CT in HL, its strengths and limitations, as well as recent efforts to implement PET/CT-based metrics as promising tools for precision medicine. Finally, the value of PET/CT for response assessment to immunotherapy is discussed.
Radiotherapy of lymphomas
2022, Cancer/Radiotherapie
Radiotherapy for Hodgkin lymphomas has evolved a lot over time, but still plays an important role, almost always in addition to chemotherapy, for the management of the early stages. The major objective is to preserve the quality of life of patients who will be cured from this disease in the vast majority of cases. Also, the personalization of the indications for the purpose of de-escalating toxicity is very refined and is essentially based on the pre- and pertherapeutic assessment by FDG-PET. The indications for radiotherapy are more limited for non-Hodgkin lymphomas, but the same principles are found, regardless of the histological type. We present the update of the recommendations of the French society of oncological radiotherapy for radiotherapy of lymphomas, which remains a very evolving field in terms of therapeutic strategy and evaluation.
La radiothérapie des lymphomes hodgkinien a beaucoup évolué au cours du temps, mais garde une place importante, presque toujours en complément de la chimiothérapie, pour la prise en charge des stades précoces. L’objectif majeur est de préserver la qualité de vie des patients qui vont guérir de cette maladie dans l’immense majorité des cas. Aussi, la personnalisation des indications dans un but de désescalade de la toxicité est très nuancée et repose essentiellement sur le bilan pré- et perthérapeutique par la TEP-TDM au fluorodésoxyglucose. Les indications de la radiothérapie sont plus limitées pour les lymphomes non-hodgkiniens, mais on retrouve les mêmes principes, quel que soit le type histologique. Cette revue présente la mise à jour des recommandations de la Société française de radiothérapie oncologique pour la radiothérapie des lymphomes, qui reste un domaine très évolutif en termes de stratégie thérapeutique et d’évaluation.
Application of high-throughput gene sequencing in lymphoma
2021, Experimental and Molecular Pathology
Citation Excerpt :
Most Hodgkin lymphomas (HLs) originate from germinal center B-cells and account for about 10% of newly diagnosed lymphomas. The annual incidence rate of HL is about 3 cases per 100, 000 population (Diehl et al., 2004). Despite advances in treatment and high curability, some patients still succumb to this disease.
As a malignant tumor originating from the lymphoid hematopoietic tissues, lymphoma has an increased incidence in recent years and has ranked among the top ten malignant tumors in the world. But until now, due to the multiple pathological subtypes and the unclear molecular mechanism, it's still difficult to make rapid diagnosis and accurate prognosis assessment for lymphoma patients. Recently, the development of high-throughput gene sequencing technology has provided the possibility to solve these clinical problems. This technology has realized large-scale screening of specific markers for lymphoma at the molecular biology level, followed by discovery of prognostic indicators and biological targets for new drug research. In this paper, we summarize the results of large-scale high-throughput gene sequencing research, and introduce the genetic changes associated with occurrence and prognosis of lymphomas with different pathological subtypes, hoping to further promote the application of this technology in clinical research of lymphoma.
Classical Hodgkin Lymphoma: Clinicopathologic Features, Prognostic Factors, and Outcomes From a 28-Year Single Institutional Experience
2021, Clinical Lymphoma, Myeloma and Leukemia
Classical Hodgkin lymphoma (cHL) is a curable malignancy, with a complete remission rate of approximately 90%. However, relapse remains a significant cause of mortality. Prognostic factors are useful in guiding therapy. This is a large, single-institution study defining the clinicopathologic features, prognostic factors, and treatment outcomes of patients with cHL.
We reviewed 727 patients with cHL treated at H. Lee Moffitt Cancer Center and Research Institute from 1990 to 2017. Data on demographics, laboratory studies, and disease statuses were collected from the institutional database and electronic medical records. Statistical analyses, overall survival (OS), progression-free survival (PFS), and multivariate analyses were performed.
The median age was 35 years. Fifty-four percent of patients were men; 45.6% had advanced stage disease; 82% were treated with ABVD (doxorubicin hydrochloride [adriamycin], bleomycin sulfate, vincristine, and dacarbazine) as frontline therapy; and 70% achieved complete response. The median PFS after first-line treatment was 16.8 years. The median OS of patients with early stage and advanced stage cHL was 19 and 12.9 years, respectively. Poor prognostic factors for OS included older age, advanced stage disease, presence of B symptoms, and a higher International Prognostic Score.
Despite high cure rates, cHL accounted for the cause of death in 47% of patients who died during follow-up. Prognostic factors, such as age, stage at diagnosis, International Prognostic Score, and B symptoms, are helpful to guide treatment. Outcomes observed in this study are comparable with those reported in previously published studies.
Contemporary treatment options for a classical disease: Advanced Hodgkin lymphoma
2020, Critical Reviews in Oncology/Hematology
Advanced classical Hodgkin lymphoma (cHL) is a rare lymphoid disease characterized by the presence of Hodgkin and Reed-Sternberg (HRS) cells. Each year, cHL accounts for 0.5% of all new cancer diagnoses and about 80% are diagnosed with advanced stage disease. Given the significant improvement in cure rates, the focus of treatment has shifted towards minimization of acute and long-term toxicities. PET-adapted strategies have largely been adopted as standard of care in the United States in an attempt to balance toxicities with adequate lymphoma control. However, the appropriate upfront chemotherapy regimen (ABVD versus eBEACOPP) remains controversial.
Hodgkin lymphoma: a review of pathological features and recent advances in pathogenesis
2020, Pathology
Hodgkin lymphoma (HL) is composed of two distinct pathological entities, nodular lymphocyte predominant HL and classic HL, the latter with four subtypes. In contrast with most other human lymphomas, in which the neoplastic cells are a major population of the tumour constituents, the neoplastic ‘Hodgkin (H) and Reed–Sternberg (RS)’ cells usually account for less than 10% of tumour bulk against an inflammatory background. The neoplastic cells of HL are of B-cell lineage (PAX5+) in virtually all cases. HL usually affects young patients with a localised nodal disease and its clinical behaviour is typically indolent. Patients respond well to chemotherapy with cure rates of 80–90% and the recent finding of PD-L1 expression, an immune checkpoint, warrants the use of immunotherapy for some patients with recurrent and/or refractory HL.
The enigmatic RS cells of HL are unique in their abundant cytoplasm and characteristic bilobed nuclei with eosinophilic prominent nucleoli, imparting an ‘owl-eye’ appearance. H cells are mononuclear variants. The viral inclusion-like morphology was a clue on the way to discovering an association between classic HL and Epstein–Barr virus (EBV). However, this association is variable in different geographic regions and in pathological subtypes, and correlates with older age (>60 years) and socioeconomic status, indicating that environmental factors are likely involved in HL pathogenesis. Virus-associated endoplasmic reticulum (ER) stress also may contribute to mechanisms underlying the characteristic morphological features of HRS cells. ER stress has been found to induce aberrant, cytoplasmic cyclin A expression, leading to nuclear hyperdiploidy. Aberrant expression of cyclin A is commonly associated with HRS cell morphology in HL, probably through EBV-latent membrane protein-1 (LMP1) signalling. Shelterin also may play a role in the morphogenesis of multinucleated RS cells. In addition, EBV-positive and -negative HL cases express survival, but not death signals of ER stress at similar levels and EBV-LMP1 transfection increases expression of survival signals in HL cell lines. These data suggest that surviving ER stress may be involved in HL pathogenesis.

View all citing articles on Scopus

: RKT and DR are both Senior Research Fellows in the Molecular Tumor Biology and Tumor Immunology group and JW is Associate Professor, all in Department I of Internal Medicine, University of Cologne, Cologne, Germany. VD is Professor Emeritus. All authors are also members of the Center for Molecular Medicine Cologne, Germany.

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ReviewPart II: Hodgkin's lymphoma—diagnosis and treatment

Summary

Section snippets

Diagnosis and staging

Prognostic factors and treatment groups

Early-stage favourable disease

The pioneers: MOPP and ABVD

Conclusion

Search strategy and selection criteria

Ann Oncol

Ann Oncol

Blood

Int J Radiat Oncol Biol Phys

Radiother Oncol

Am J Med

Blood

Ann Oncol

Ann Oncol

Ann Oncol

Blood

Am J Med

Blood

Lancet

Lancet

Blood

Blood

Blood

Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting

J Clin Oncol

A prognostic score for advanced Hodgkin's disease. International Prognostic Factors Project on Advanced Hodgkin's Disease

N Engl J Med

Two cycles ABVD plus extended field radiotherpay is superior to radiotherpay alone in early stage Hodgkin's disease: Results of the German Hodgkin's Lymphoma study group (GHSH) trial HD7

Blood

Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherpay in patients with early stage unfavourable Hodgkin's lymphoma: results of the HD8 trial of the German Hodgkin's Lymphoma Study Group

J Clin Oncol

Hodgkin's disease

N Engl J Med

Twenty years of MOPP therapy for Hodgkin's disease

J Clin Oncol

Review
Part II: Hodgkin's lymphoma—diagnosis and treatment