Management is mostly dependent on the stage of disease, favourable/unfavourable status, and the underlying type of Hodgkin's lymphoma.

Favourable disease includes patients without B symptoms, non-bulky disease, low ESR (< 50) and less than 3 or 4 lymph node regions involved depending on the system used (EORTC < 4 sites, GHSG < 3 sites). Age < 50 is only important for EORTC staging. Favourable disease as defined by the GHSG is particularly important when considering low dose therapy for favourable disease.

For advanced disease, an "International Prognostic Score" IPS is generated, by adding one point for each of the following risk factors.

  • Albumin < 40 g/L
  • Hb < 105
  • Male
  • Age > 45
  • Stage IV
  • White cell count > 15x10^9 per L
  • Lymphocyte count

IPS of 4 or more is considered "high risk" disease and is often treated with more intensive chemotherapy regimens (eg. BEACOPP, Stanford V).

Hodgkin's Lymphoma is staged via the Costwald System:

  • Stage I - Single lymph node region or organ (eg. thymus, spleen or Waldeyer's ring)
  • Stage II - Multiple nodal regions on one side of the diaphragm
  • Stage III - Multiple lymph node regions on both sides of the diaphragm. Involvement of the spleen in addition to supra-diaphragmatic disease is IIIS. Involvement of another extranodal side is IIIE. Involvement of the liver, spleen and mediastinal lymph nodes would be IIIES
  • Stage IV - Diffuse involvement of one or more extra-lymphatic organs (eg. bone marrow, liver)

Additional suffixes are added to denote specific prognostic information:

  • Presence of B symptoms is denoted by "B", absence by "A"
  • Involvement of an extranodal site is denoted by "E". If disease arises within an extranodal site with no evidence of distant disease, then the disease is IE. If the disease arises in a single lymph node region that directly invades an extranodal site, the disease is IE. If there is diffuse involvement of an organ (eg. multiple liver lesions as opposed to a para-aortic mass invading the liver) then the disease is stage IV.
  • Bulky disease is denoted by an X. Bulky disease has a variable definition, from > 5 cm to > 10 cm.
  • Splenic involvement as the only site of disease below the diaphragm in stage III disease is given the "S" suffix

Some examples:

  • Disease arising in the thymus with no B symptoms and < 10 cm: Stage IA
  • Disease arising in Waldeyer's ring with cervical lymph node involvement and B symptoms: Stage IIB
  • Mediastinal disease > 10 cm with splenic involvement: Stage IIIASX
  • Mediastinal disease invading the parenchyma of the right lung through direct invasion, no B symptoms: Stage IE
  • Disease arising as a discrete area in the skin: Stage IE
  • Disease with bone marrow involvement: Stage IV

Localised (Stage I-II), Favourable

Patients with localised favourable disease are conventially treated with:

  • 4 cycles of Adriamycin/Bleomycin/Vinblastine/Dacarbazine (ABVD), where each cycle involves two doses of ABVD 14 days apart (ie. monthly cycles)
  • Involved field radiotherapy to 30 Gy

The GHSG randomised patients on 2 x 2 fashion between 2 and 4 cycles of ABVD and 20 and 30 Gy of involved field radiotherapy. The overall survival and disease free survival were identical and radiotherapy toxicity was significantly reduced in the arms receiving 20 Gy instead of 30 Gy. This has led to the adoption of this technique in patients with favourable disease as defined by the GHSG (< 3 sites, non-bulky, ESR < 50 or < 30 when B symptoms present).

In the past MOPP was used (mechlorethamine, vincristine, procarbicine, prednisolone) but ABVD provides less toxicity and higher progression free survival rates. There is significanly less myelotoxicity and infertility with ABVD vs MOPP, and ABVD also shows improved disease control than MOPP.

Chemotherapy Alone

Chemotherapy alone is used by some groups (particularly by secretive haematologists who hide their patients…). There are a number of trials but data is compromised by poor radiotherapy technique (ie. use of subtotal radiotherapy + chemotherapy compared to chemotherapy alone, or higher than usual dose), higher rates of disease recurrence (but no overall survival difference) and a mix of chemotherapy regimens. An example is the HD6 trial which demonstrated poorer disease free survival but better overall survival. Patients who relapse with chemotherapy alone require intensive salvage chemotherapy, often entailing an autologous bone marrow transplant.

Radiotherapy Alone

Radiotherapy alone is inferior to combined chemotherapy and radiotherapy in both toxicity and disease control (H8F trial). Subtotal radiotherapy is superior to involved field radiotherapy when radiotherapy is given alone, and this remains a potential technique for patients unable to receive or who refuse chemotherapy. This is, therefore, a very rare and unlikely to be encountered scenario.

Localised, Unfavourable Disease

These are patients with bulky disease, high ESR (> 50, or > 30 with B symptoms), or more than 2 lymph node regions involved. They require more intensive treatment than the favouable group. This group is often subdivided into those with unfavourable bulky disease and those with unfavourable but non-bulky disease. There are some who call for radiotherapy to be omitted for patients with non-bulky disease but there is no convinving evidence to support this; most studies of omitting radiotherapy were done in the favourable risk group of patients and radiotherapy techniques were often outdated (eg. extended field irradiation).
Regardless of tuour bulk, patients should be treated with systemic therapy. Conventionally this is ABVD, although some centres advocate Stanford V or BEACOPP. Convention is that 4 cycles of ABVD are given, followed by restaging. If a complete response has occurred, then either involved field radiotherapy is given or alternatively two further cycles of ABVD followed by involved field radiotherapy. Patients with partial response or stable disease should definitely have 6 cycles of ABVD, followed by involved field radiotherapy. Patients with progressive disease at any point, or with partial response or stable disease after radiotherapy, should be considered for intensification of therapy with autologous stem cell transplant.

Advanced Disease (Stage III-IV)

6 cycles of ABVD is the most commonly used regimen; additional cycles (up to 8) may be used when disease is slow to respond. Other regimens include:

  • Stanford V (Doxorubicin, vinblastine, mechloretamine, etoposide, vincristine, bleomycin, prednisolone) is given over 12 weeks (as opposed to at least 24 with ABVD), with patients receiving radiotherapy to bulky sites. The Stanford protocol defines bulky disease as > 5 cm. There is no evidence that Stanford V is superior to ABVD and therefore ABVD remains standard of care; Stanford V may be best used in low risk patients (IPS < 4) who would likely receive radiotherapy anyway.
  • Escalated BEACOPP shows improved progression free survival but no difference in overall survival when comapred to ABVD. There are increased toxicities with escalated BEACOPP, including infections during treatment, prolonged hospital stay, and long term risks of myelodysplastic syndrome. There is a suggestion that BEACOPP may be more effective in high risk patients (IPS 4+).


  • ABVD is the standard of care
  • Stanford V may be used for patients likely to require RT, who are not able to tolerate the higher doses of ABVD, who desire shorter treatment, and have a low IPS score
  • BEACOPP may be used for patients with high risk disease (IPS 4+) but is associated with increased toxicity.

Role of Radiotherapy in Advanced Disease

This is a controversial area. Radiotherapy was previously the only treatment used for advanced lymphoma (total lymphatic irradiation or subtotal lymphatic irradiation) but use of this regimen is almost non-existent in the modern age. Radiotherapy definitely has a role to play when Stanford V is used, by delivering a dose of 36 Gy in 20 fractions to the areas of bulky (> 5 cm) disease as well as to the spleen if it is macroscopically involved.
After ABVD, there is conflicting opinion. For stage III/IV disease that undergoes a complete response, there is randomised data that supports omission of radiotherapy with similar disease outcomes and a trend towards higher rates of second malignancy in the patients treated with radiotherapy. This study is criticised for use of an older chemotherapy regimen, 8 cycles, non-randomisation of bulky disease patients, and poor rates of complete response. For patients with partial response, there is a definite role for radiotherapy to those sites. There is retrospective data supporting the role for radiotherapy to sites of bulky disease (> 10 cm) in advanced data but no randomised evidence. Therefore, for ABVD radiotherapy is usually only used when patients have bulky disease in the mediastinum at presentation.
After BEACOPP, patients with PET negative disease have a 5% risk of local recurrence. PET positive patients (ie. partial response) benefit from radiotherapy to those sites.

In summary, radiotherapy is controversial for patients who receive ABVD chemotherapy, and is usually only employed if there has only been a partial response or if bulky mediastinal disease was present at diagnosis. It is only used for PET-positive patients after BEACOPP therapy. It is used in all Stanford V patients who have disease > 5 cm.

Relapsed or Refractory Disease

Most patients will respond to initial treatment. Rarely, patients may fail first line therapy and develop progressive disease at this time; in these situations second line systemic therapy followed by autologous stem cell transplant is indicated.
Patients who relapse within 1 year of completing treatment are also unlikely to be cured without stem cell transplant. Treatment is aimed at inducing a second remission and following this with autologous stem cell transplant. Patients who relapse after 1 year with small volumes of disease may be treated with systemic therapy alone +/- radiotherapy depending on the site and previous treatments.
If remission is unachievable palliation is usually required.

Lymphocyte Predominate Hodgkin's Lymphoma

This uncommon form (5%) of Hodgkin's lymphoma is associated with a better prognosis, indolent disease behaviour and excellent response to treatment. There is a low risk of disease outside of the initially involved lymph node groups, making local therapy more important than in classical Hodgkin's lymphoma. Radiotherapy therefore plays an essential role in the management of early stage disease.
Involved field radiotherapy has been proven equivalent to extended field radiotherapy and/or chemotherapy for early stage disease.
The typical dose is 36 Gy.

Advanced LPHL

Chemotherapy is the mainstay of treatment. ABVD is most commonly used based on experience with classical Hodgkin's disease.
LPHL almost always expresses CD20 and rituximab can be used for relapsed/refractory disease.


About 3% of cases of Hodgkin's Lymphoma occur during pregnancy. This presents special issues with regards to staging and treatment, which in general attempt to limit potential toxicity to the fetus.


CT and PET both give excessive dose to the fetus (particularly PET), making these tools less desirable for staging. The development of MRI has allowed adequate assessment of the abdomen. Ultrasound can also be used to judge size of cervical and axillary lymph nodes. Clinical examination is significantly important in this population.
ESR, often used to determine 'favourable' and 'unfavourable' classification for stage I and II Hodgkin's disease, is frequently elevated during pregnancy.


The most critical time for therapeutic complications is the first trimester, particularly during implantation and organogenesis (weeks 1-8). This applies to both chemotherapy and radiotherapy. Treatment with systemic therapy during the first trimester is best avoided.
Treatment in the second and third trimester is less problematic (unlikely teratogenecity) but may lead to stillbirth, reduced head circumference, mental retardation and elevated cancer risk in childhood.
Importantly, despite a low volume of data, there are many successful case series of women treated at any stage of pregnancy with ABVD or single agent vinblastine with good survival reported in the patients and no problems reported in offspring.
In general:

  • Delay treatment if safe, particularly in the first trimester. Unsafe situations include airway obstruction or spinal cord compression.
  • Liaise with obstetrician regarding safe delivery time
  • Chemotherapy with ABVD has been used in pregnant patients with low rates of toxicity reported
  • Radiotherapy to the mediastinum and cervical regions has been delivered with no adverse outcomes reported; 5 HVL layers of lead were used over the abdomen to reduce foetal exposure.
  • Avoid radiotherapy to the pelvis