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Hodgkin's lymphoma

Medical Professionals

Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Hodgkin's lymphoma article more useful, or one of our other health articles.

Synonym: Hodgkin's disease

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What is Hodgkin's lymphoma?

Hodgkin's lymphoma is a malignant tumour of the lymphatic system that is characterised histologically by the presence of multinucleated giant cells (Reed-Sternberg cells) and associated abnormal and smaller mononuclear cells originating from B lymphocytes in the germinal centres of lymphoid tissue.


Accurate classification of the type and accurate staging of the disease will determine the most favourable treatment options and prognosis. Hodgkin's lymphoma is classified into two distinct entities:1

  • Classical Hodgkin's lymphoma (more common):

    • Nodular sclerosis.

    • Mixed cellularity.

    • Lymphocyte-rich.

    • Lymphocyte-depleted.

  • Nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL).

There is no difference in the prognosis or management of the different subtypes of classical Hodgkin's lymphoma. In Europe and North America, nodular sclerosis classical Hodgkin's lymphoma accounts for 70% of all classical Hodgkin's lymphoma. Lymphocyte-depleted classical Hodgkin's lymphoma is more prevalent in immunocompromised patients and is seen more commonly in developing countries, where it has a strong association with Epstein-Barr virus (EBV) infection.2

NLPHL is distinct histologically and Reed-Sternberg cells are not present, it has a risk of transformation to high-grade non-Hodgkin's lymphoma and is managed differently from classical Hodgkin's lymphoma. The rest of this article is about classical Hodgkin's lymphoma.

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How common is Hodgkin's lymphoma? (Epidemiology)2

  • The annual incidence of Hodgkin's lymphoma in the UK is 2.7/100,000 with a slight male predominance.

  • There is a peak in incidence in young adults aged 20-34 years, with a further peak observed over 70 years.

Risk factors

  • EBV has been found in the Reed-Sternberg cells of about 50% of patients with Hodgkin's lymphoma.

  • Patients who have previously developed mononucleosis have an increased risk of developing Hodgkin's lymphoma.

  • Other risk factors include human immunodeficiency virus (HIV), immunosuppression and cigarette smoking.

Symptoms of Hodgkin's lymphoma (presentation)

  • Most patients present with an enlarged but otherwise asymptomatic lymph node, typically in the lower neck or supraclavicular region.

  • Mediastinal masses are frequent and are sometimes discovered on a routine CXR.

  • Patients might complain of chest discomfort with a cough or dyspnoea.

  • Systemic symptoms of drenching night sweats, unexplained fever >38°C, and weight loss of >10% over six months, are termed B symptoms and are identified in approximately 25% of patients.2

  • Alcohol-induced pain at sites of nodal disease is specific but occurs in fewer than 10% of patients.

  • Findings on examination include lymphadenopathy, hepatomegaly, splenomegaly, and superior vena cava syndrome; there may also be features caused by paraneoplastic syndromes - eg, cerebellar degeneration, neuropathy or Guillain-Barré syndrome.

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The National Institute for Health and Care Excellence (NICE) provides separate recommendations for adults and for children and young people to reflect that there are different referral pathways. Young people (aged 16 to 24) may be referred using either pathway depending on their age and local arrangements.

  • Consider a suspected cancer pathway referral for Hodgkin's lymphoma in adults presenting with unexplained lymphadenopathy.

  • When considering referral, take into account any associated symptoms, particularly fever, night sweats, shortness of breath, pruritus, weight loss or alcohol-induced lymph node pain.

NICE has recommended that a person should receive a diagnosis or ruling out of cancer within 28 days of being referred urgently by their GP for suspected cancer.

Children and young people

  • Consider a very urgent referral (for an appointment within 48 hours) for specialist assessment for Hodgkin's lymphoma in children and young people presenting with unexplained lymphadenopathy.

  • When considering referral, take into account any associated symptoms, particularly fever, night sweats, shortness of breath, pruritus or weight loss.

Differential diagnosis

Diagnosing Hodgkin's lymphoma (investigations)2 4

  • FBC: to exclude leukaemia, mononucleosis and other causes of lymphadenopathy. The degree of any anaemia, leukocytosis and lymphopenia are prognostic indicators.

  • Tests for possible differential diagnoses - eg, tests for infectious mononucleosis.

  • ESR: an ESR of greater than 70 carries an unfavourable prognosis.

  • Liver function and serum protein tests: the level of any rise in lactate dehydrogenase (LDH) and fall in albumin levels has prognostic significance.

  • HIV tests are necessary in patients with suspected Hodgkin's lymphoma.

  • Fine needle aspiration samples should not normally be used as the sole tissue for diagnosis.

  • Lymph node biopsy:

    • Pathological diagnosis should be made from a sufficiently large specimen or excisional lymph node biopsy to provide samples for fresh frozen and formalin-fixed samples.

    • Excisional node biopsy is better than fine needle or core needle biopsy, as it allows the diagnosis of lymphomas based on the morphology of the lymph node, which is not offered by needle biopsy.

  • CXR: assess any intrathoracic lymphadenopathy and mediastinal expansion.

  • CT scans of the thorax and abdomen are required for staging Hodgkin's lymphoma.

  • Lymphangiography: may be useful if there is subdiaphragmatic presentation of Hodgkin's lymphoma with equivocal abdominal CT findings, or there is subdiaphragmatic presentation of Hodgkin's lymphoma with the intention to treat with radiotherapy alone.

  • Gallium scans: can be useful if CT scanning produces equivocal results. They are performed if mediastinal or hilar nodes are involved and as a baseline in patients with bulky disease, for better determination of response during and after therapy.

  • Bone marrow biopsy is indicated for staging purposes.

Staging and risk assessment

  • Blood evaluation should include full blood count, ESR, renal function, liver function, bone profile, testing for HIV, and hepatitis B and C serology.

  • Positron emission tomography (PET) staging is recommended. A bone-marrow biopsy is usually not required. Staging laparotomy is not recommended.

  • Early-stage patients should be classified as favourable or unfavourable.

  • Advanced-stage patients should be allocated an International Prognostic Score (IPS).
    Patients should be offered fertility preservation/counselling where appropriate.

Stages of Hodgkin's lymphoma

Patients with early-stage disease should be classified into favourable or unfavourable prognosis, depending on the presence or absence of mediastinal adenopathy, presence of symptoms, level of ESR and number of lymph node sites involved.2

Ann Arbor staging system for Hodgkin's lymphoma:

  • Stage I: involvement of one lymph-node region or lymphoid structure (eg, spleen, thymus, Waldeyer's ring).

  • Stage II: two or more lymph-node regions on the same side of the diaphragm.

  • Stage III: lymph nodes on both sides of the diaphragm.

    • Stage III (1): with splenic, hilar, coeliac, or portal nodes.

    • Stage III (2): with para-aortic, iliac, or mesenteric nodes.

  • Stage IV: involvement of extranodal site(s) beyond that designated E (see below).

  • Modifying features:

    • A: no symptoms.

    • B: fever, drenching night sweats, weight loss greater than 10% in six months.

    • X: bulky disease: greater than a third widening of mediastinum or greater than 10 cm maximum diameter of nodal mass.

    • E: involvement of single, contiguous, or proximal extranodal site.

Disease is further classified into limited, intermediate or advanced:

  • Limited disease: up to IIB with no risk factors.

  • Intermediate disease: up to IIB with at least three involved lymph-node areas or high ESR (ESR over 50 mm/h without B symptoms, or over 30 mm/h with B symptoms; B symptoms are defined as fever, night sweat, weight loss).

  • Advanced disease:

    • Stage IIB with large mediastinal mass (more than one third of the horizontal chest diameter) or extranodal disease.

    • Any stage III or above.

Management of Hodgkin's lymphoma2 4 5

Before treatment, patients should be assessed for risk of acute and/or long-term complications. Cardiac and pulmonary function tests are mandatory, and consultation with an ear, nose and throat specialist should be considered (particularly for patients with involvement of the head and neck region).

The patient may also need reproductive counselling if they have not yet started a family, as treatment may compromise fertility. For male patients, pre-treatment semen cryopreservation should be offered where possible. For female patients, pre-treatment review of options with a fertility specialist should be considered.

Initial therapy is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early-stage disease are typically treated with combined modality strategies with courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced-stage disease receive a longer course of chemotherapy often without radiation therapy. Newer agents including brentuximab vedotin are now being incorporated into frontline therapy and these new combinations are becoming a standard of care.

High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD-1 blockade, non-myeloablative allogeneic transplant or participation in a clinical trial should be considered.

Both chemotherapy and radiation therapy increase the risk of developing secondary solid tumours - eg, cancers of the lung, breast, and stomach.

Vaccinations: polyvalent pneumococcal vaccine and influenza vaccine should be given to all patients with Hodgkin's lymphoma. Meningococcal group C conjugate vaccine and Haemophilus influenzae type b vaccine are also recommended, especially for patients receiving treatment and those with asplenia or splenic dysfunction.6


  • Effective but carries an increased risk of leukaemia. The peak in risk is seen about five years after the initiation of chemotherapy. The risk is higher in patients who undergo splenectomy and who have advanced disease; the risk is unaffected by concomitant radiation therapy.

  • Chemotherapy is normally based on certain combinations:

    • ABVD: doxorubicin (used to be called Adriamycin®), bleomycin, vinblastine and dacarbazine.

    • BEACOPP: consists of bleomycin, etoposide, doxorubicin (Adriamycin®), cyclophosphamide, vincristine (Oncovin®), procarbazine and prednisolone.

    • If therapy is required in pregnancy, the general consensus is that ABVD is the regimen of choice if multi-agent chemotherapy is to be used.

  • Any patient with severe neutropenia should be given antibiotic prophylaxis with chemotherapy. Neutropenia should not delay ABVD delivery for the majority of patients.

  • Recombinant human granulocyte colony-stimulating factor (rhG-CSF) stimulates the production of neutrophils and may reduce the duration of chemotherapy-induced neutropenia and thereby reduce the incidence of associated sepsis.6


  • Involved-site radiotherapy (ISRT) is the standard of care for HL treated with combined-modality therapy.

  • The dose for favourable (GHSG) early-stage disease should be 20 Gy.

  • The dose for most other indications is 30 Gy, but for partial responses a boost to 36– 45 Gy may be considered.

Treatment regimes

There is some variation between the different guidelines and local guidelines should always be followed. The following regimes are recommended by the British Society of Haematology. The choice of treatment will depend on the stage of the disease, the histological subtype and favourable prognostic factors:

Early-stage disease:
Early favourable disease:

  • Start with 2 cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) followed by an interim PET scan.

  • For early favourable disease and a negative interim PET scan, a total of 2–3 cycles of ABVD followed by radiotherapy. For early favourable disease and a negative interim PET scan, it may be appropriate to omit radiotherapy following discussion with a radiation oncologist. These patients should receive a total of 3 or 4 cycles of ABVD.

Early unfavourable disease:

  • 2 cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisolone (eBEACOPP) and 2 cycles of ABVD followed by a PET.

  • With a positive scan, patients should be offered radiotherapy. For early unfavourable disease, an alternative standard is 2 cycles of ABVD followed by interim PET.

  • If interim PET-negative, patients have 1–2 further cycles of ABVD with radiotherapy or complete a total of 6 cycles of chemotherapy with the last four being AVD without radiotherapy.

  • For early-stage disease with a positive PET scan after 2 cycles of ABVD, consider 2 cycles of eBEACOPP followed by radiotherapy.

PET/CT response should be reported according to Deauville criteria: a Deauville score (DS) of 1 or 2 is ‘negative’ and 4 or 5 ‘positive’. DS 1–3 is considered complete metabolic response.

Advanced-stage disease:

  • Aged up to 60 years with advanced-stage HL: either ABVD or eBEACOPP with an interim PET scan after 2 cycles.

  • ABVD-treated patients:

    • If interim PET is negative (D1–3), bleomycin should be omitted from the remaining 4 cycles of treatment. The benefits of radiotherapy remain uncertain but may be considered.

    • If the interim PET is positive (D4–5) without progression, then intensification to 4 cycles of eBEACOPP should be considered.

    • If iPET is positive (D4–5), end-of-treatment radiotherapy should be considered.

  • eBEACOPP-treated patients:

    • Substituting procarbazine for dacarbazine is reasonable.

    • If interim PET is negative (D1–3) only 2 further cycles of eBEACOPP should be administered, or alternatively patients can be de-escalated to ABVD × 4 with no requirement for radiotherapy consolidation.

    • If the interim PET is positive (D4–5) patients should complete a total of 6 cycles of eBEACOPP.

  • For all patients who are interim PET-positive (D4–5), an end-of-treatment PET scan is indicated and if positive, patients should be considered for biopsy or interval scanning and/or radiotherapy.

  • Patients who develop progressive disease on therapy should be considered for treatment intensification with transplantation.

Teenagers and young adults

  • Long-term risks of organ toxicity, secondary cancer and impact on fertility should be discussed.

  • Referral to a fertility specialist/for fertility preservation should always be offered, if timing permits prior to treatment.


  • Delaying commencement of chemotherapy until post delivery would not be standard practice and should be done with caution.

  • ABVD is preferred unless specifically contra-indicated.

  • Radiotherapy should be delayed until after delivery if possible.

Elderly patients

  • Elderly patients should be formally assessed for fitness to receive combination chemotherapy with a comorbidity assessment.

  • ‘Frail’ patients should not usually be offered conventional anthracycline-based combination chemotherapy; chlorambucil, vinblastine, procarbazine and prednisolone (ChlVPP) may be appropriate.

  • ‘Non-frail’ patients should be offered anthracycline-based combination chemotherapy with or without radiotherapy with the aim of achieving complete remission. Treating elderly non-frail patients with ABVD may be reasonable, but the use of bleomycin requires extreme caution and AVD is preferred.

  • Limiting ABVD to 3 cycles, if this achieves PET negativity, may be appropriate for early and advanced-stage elderly patients.

  • Alternative anthracycline-containing regimens including cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) and doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisolone (ACOPP) may be appropriate.

Primary resistant and relapsed classical Hodgkin's lymphoma7

  • Repeat biopsy is recommended for patients thought to have relapsed, and should be considered in those who have residual lesions after treatment. PET/CT is the preferred restaging modality after salvage therapy (high-dose chemotherapy).

  • ASCT is the standard treatment for patients with primary resistant disease or with relapsed disease who achieve an adequate response to salvage chemotherapy. ASCT is not recommended in those failing to achieve an adequate response.

  • The choice of a first-line salvage regime in patients eligible for ASCT should be based on individual patient factors. Regimens containing stem cell toxic agents (eg, carmustine and melphalan) should be avoided if possible until stem cells have been successfully collected and cryopreserved if ASCT is planned.

  • In patients not eligible for ASCT, combined therapy (chemotherapy and radiotherapy) should be considered especially in:

    • Early-stage relapse.

    • Patients who have not received prior radiotherapy or who have relapsed outside of the initial radiotherapy field.

  • In patients unlikely to tolerate the toxicities associated with more intensive regimens, palliation with either a single agent or with a multi-agent oral regimen with or without intravenous vinblastine should be considered.

  • Early consideration of involvement of palliative care services is recommended, particularly in those not eligible for high-dose therapy.

  • For patients who do not respond to high-dose chemotherapy with ASCT, brentuximab vedotin, palliative chemotherapy, non-myeloablative allogeneic transplant or participation in a clinical trial should be considered.8 9

  • Allogeneic transplantation using a reduced-intensity conditioning regimen is the treatment of choice for younger patients with a suitable donor and chemo-sensitive disease following failure of ASCT.

  • A second autologous transplant is a reasonable clinical option in selected patients with late relapse following ASCT.

  • The use of radiotherapy should be considered in cases of local relapse or relapse at sites where local disease is dominating the clinical picture.

  • Salvage radiotherapy alone may be considered a reasonable treatment option in selected patients not eligible for ASCT, especially for older patients with relapsed Hodgkin's lymphoma with a favourable prognosis and limited-stage disease at relapse.

Editor's note

Dr Krishna Vakharia, 14th May 2024

Pembrolizumab for treating relapsed or refractory classical Hodgkin lymphoma in people 3 years and over 10

NICE has recommended pembrolizumab as an option for treating relapsed or refractory classical Hodgkin lymphoma in people 3 years and over who have had at least 2 previous treatments and cannot have an autologous stem cell transplant (ASCT). It is recommended only if they have already had brentuximab vedotin and pembrolizumab is stopped after 2 years of treatment or earlier if the person has a stem cell transplant or the disease progresses.

When people with relapsed or refractory classical Hodgkin lymphoma cannot have an ASCT, they can have brentuximab vedotin. After that, they have standard care, which includes chemotherapy and radiotherapy. Pembrolizumab would be offered instead of standard care and stopped after 2 years or earlier if the person's condition gets worse or they are able to have a stem cell transplant. Indirect comparisons suggest that people who have pembrolizumab live longer.


  • Patients are usually followed up for at least 2 years following first-line therapy. There is no proven role for surveillance CT or PET.

  • Patients should be made aware that they are at an increased lifetime risk of second neoplasms, cardiovascular and pulmonary disease and infertility.

  • Patients should have follow-up discussions about the impact of treatment on their fertility and/or menopausal status.

  • Regular lifestyle advice should be offered to reduce the secondary neoplasms and cardiovascular risk, including complete avoidance of smoking and management of cardiovascular risks such as hypertension, diabetes mellitus and hyperlipidaemia.

  • Women treated with radiotherapy to breast tissue under the age of 36 years should be offered breast screening starting eight years after radiotherapy or at age 25, whichever is later.

  • Patients who have had radiotherapy to the neck and upper mediastinum should have regular thyroid function checks. Hypothyroidism can occur up to 30 years after radiotherapy.

  • Patients should only receive irradiated blood products for the rest of their lives.

Complications of Hodgkin's lymphoma

  • Leukaemia, especially acute myeloid leukaemia, may occur in patients treated with chemotherapy or combined chemotherapy and radiotherapy.

  • Second solid tumours, especially of the colon, lung, bone, breast, and thyroid, can occur in patients who received radiation therapy with or without chemotherapy.11 Cancer screening should be conducted regularly.

  • The risk of breast cancer is greatest in women treated with supradiaphragmatic radiotherapy (SRT) during adolescence and young adulthood, although an increase in risk is shown in most studies with SRT up to the age of 30-40 years, which persists for at least 20-25 years after treatment.12

  • An increased risk has also been found for melanoma, non-Hodgkin's lymphoma, soft-tissue sarcoma, salivary gland cancers and pancreatic cancer.

  • Other complications of irradiation include hypothyroidism and cardiovascular disease.

  • Other complications of chemotherapy include male infertility and female infertility.


  • Both localised and advanced Hodgkin's lymphoma can be cured in most patients.

  • With modern treatment strategies, 80-90% of patients achieve permanent remission and can be considered cured.13

  • Poor prognostic indicators include:14

    • Increasing tumour burden and extension of disease.

    • Increasing age.

    • Male.

    • Constitutional symptoms (unexplained fever above 38°C, drenching night sweats and weight loss).

    • Anaemia, leukocytosis, lymphopenia, monocytosis.

    • Low levels of serum albumin.

    • Increasing ESR.

    • Elevated beta-2 microglobulin.

    • Biohumoral factors (IL-10, IL-6, sCD30, TNF, TARC).

    • Circulating DNA of cellular and viral (EBV) origin.

    • Genetic background.

  • Despite the high cure rates, long-term survivors have increased mortality:2

    • During the first 5-10 years of follow-up, the main cause of increased mortality is the disease itself, especially in those with unfavourable prognosis.

    • However, mortality remains significantly elevated more than 20 years after treatment. The main causes of long-term, non-relapse morbidity and mortality are second neoplasms and cardiac disease, but also include pulmonary disease and infections.

Further reading and references

  1. Jiang M, Bennani NN, Feldman AL; Lymphoma classification update: T-cell lymphomas, Hodgkin lymphomas, and histiocytic/dendritic cell neoplasms. Expert Rev Hematol. 2017 Mar;10(3):239-249. doi: 10.1080/17474086.2017.1281122. Epub 2017 Jan 29.
  2. Guideline for the first-line management of Classical Hodgkin Lymphoma; British Society for Haematology. February 2022.
  3. Suspected cancer: recognition and referral; NICE guideline (2015 - last updated October 2023)
  4. Follows GA, Ardeshna KM, Barrington SF, et al; Guidelines for the first line management of classical Hodgkin lymphoma. Br J Haematol. 2014 Jul;166(1):34-49. doi: 10.1111/bjh.12878. Epub 2014 Apr 9.
  5. Ansell SM; Hodgkin lymphoma: 2018 update on diagnosis, risk-stratification, and management. Am J Hematol. 2018 May;93(5):704-715. doi: 10.1002/ajh.25071.
  6. British National Formulary (BNF); NICE Evidence Services (UK access only)
  7. Guideline on the Management of Primary Resistant and Relapsed Classical Hodgkin Lymphoma; British Committee for Standards in Haematology and the British Society of Blood and Marrow Transplantation (2013)
  8. Ansell SM; Hodgkin lymphoma: 2012 update on diagnosis, risk-stratification, and management. Am J Hematol. 2012 Dec;87(12):1096-103. doi: 10.1002/ajh.23348.
  9. Furtado M, Rule S; Emerging Pharmacotherapy for Relapsed or Refractory Hodgkin's Lymphoma: Focus on Brentuximab Vedotin. Clin Med Insights Oncol. 2012;6:31-9. Epub 2012 Jan 4.
  10. Pembrolizumab for treating relapsed or refractory classical Hodgkin lymphoma in people 3 years and over; NICE Technology appraisal guidance, May 2024
  11. Hodgson DC; Late effects in the era of modern therapy for Hodgkin lymphoma. Hematology Am Soc Hematol Educ Program. 2011;2011:323-9.
  12. Howell SJ, Searle C, Goode V, et al; The UK national breast cancer screening programme for survivors of Hodgkin lymphoma detects breast cancer at an early stage. Br J Cancer. 2009 Aug 18;101(4):582-8. doi: 10.1038/sj.bjc.6605215.
  13. Hodgkin's lymphoma: ESMO Clinical Practice Guidelines for diagnosis treatment and follow-up; European Society for Medical Oncology (2018)
  14. Cuccaro A, Bartolomei F, Cupelli E, et al; Prognostic factors in hodgkin lymphoma. Mediterr J Hematol Infect Dis. 2014 Jul 5;6(1):e2014053. doi: 10.4084/MJHID.2014.053. eCollection 2014.

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