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Early-stage classical Hodgkin lymphoma is Hodgkin lymphoma confined to one or two lymph node regions on one side of the diaphragm, one of the most curable cancers, with most patients cured by a short course of ABVD chemotherapy with or without radiotherapy to the involved nodes. Because patients are young, trials now use PET scans after two cycles to give as little treatment as safely possible.
Classical Hodgkin lymphoma is a B-cell lymphoma in which the malignant Hodgkin and Reed-Sternberg cells, CD30 and CD15 positive and usually CD20 negative, are outnumbered by a reactive inflammatory background; nodular sclerosis is the commonest subtype in young adults, and PD-L1 amplification at 9p24.1 is near universal. Stage I and II disease is divided into favourable and unfavourable groups by the presence of bulky disease, raised erythrocyte sedimentation rate, B symptoms, three or more nodal sites or extranodal extension, definitions that differ slightly between the German Hodgkin Study Group (GHSG) and the EORTC. Radiotherapy alone cured most patients with early disease from the 1960s, but the second cancers and heart disease it caused decades later drove the shift to combined chemotherapy with smaller radiation fields and lower doses.
GHSG HD10 (New England Journal of Medicine 2010) showed that two cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) with 20 Gy of involved-field radiotherapy was enough for favourable disease, and HD11 and HD14 defined four cycles of chemotherapy (or two escalated BEACOPP plus two ABVD) with 30 Gy for unfavourable disease. Interim PET then became the tool for de-escalation: the RAPID trial (New England Journal of Medicine 2015) and EORTC H10 showed that omitting radiotherapy in patients who were PET-negative after two or three ABVD cycles costs a few percentage points of progression-free survival without a survival difference, and HD16 and HD17 refined which PET-negative patients can safely skip radiotherapy, so today many patients receive chemotherapy alone and the rest involved-site radiotherapy with modern conformal or proton techniques that spare the heart and breasts. Brentuximab vedotin and PD-1 antibodies, established in advanced disease, are moving into early-stage trials: the Children's Oncology Group AHOD2131 trial compares brentuximab vedotin with nivolumab against standard chemotherapy in early-stage high-risk disease in patients from age 5 to 60, and the GHSG HD21 and NIVAHL programmes test PD-1 antibodies with reduced chemotherapy. Fertility preservation, cardiac protection and lifelong survivorship care, including breast screening for women irradiated young, are part of standard management.
About half of classical Hodgkin lymphoma, typically in young adults with painless neck or mediastinal nodes; cure rates exceed nine in ten, so the modern problem is avoiding late harm from treatment.
Leukaemias, myeloma and MDS live in the marrow and blood; lymphomas grow in lymph nodes and spleen. The node stations are the disease map, not a route of spread, and staging counts them.
In lymphoma the node stations are the disease itself; staging (Ann Arbor / Lugano) counts how many regions and sides of the diaphragm are involved.
Same organ: High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma), Mediastinal grey zone lymphoma, Primary effusion lymphoma, Plasmablastic lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, EBV-positive diffuse large B-cell lymphoma, Primary large B-cell lymphoma of the testis, Gastric MALT lymphoma, Ocular adnexal MALT lymphoma, Extranodal NK/T-cell lymphoma, Adult T-cell leukaemia/lymphoma, ALK-positive anaplastic large cell lymphoma, ALK-negative anaplastic large cell lymphoma, Breast implant-associated anaplastic large cell lymphoma, Primary cutaneous anaplastic large cell lymphoma, Lymphomatoid papulosis, Mycosis fungoides, Enteropathy-associated T-cell lymphoma, Monomorphic epitheliotropic intestinal T-cell lymphoma, Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), Splenic marginal zone lymphoma, Nodal marginal zone lymphoma, Primary cutaneous marginal zone lymphoma, Primary cutaneous follicle centre lymphoma, Sezary syndrome, Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma), Hepatosplenic T-cell lymphoma, Intravascular large B-cell lymphoma, Lymphomatoid granulomatosis, T-cell prolymphocytic leukaemia, Splenic B-cell lymphoma/leukaemia with prominent nucleoli (formerly B-cell prolymphocytic leukaemia and hairy cell leukaemia variant), T-cell large granular lymphocytic leukaemia, Mixed-phenotype acute leukaemia, Myeloid leukaemia of Down syndrome, Burkitt leukaemia, Marginal zone lymphoma, Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome), Primary mediastinal (thymic) large B-cell lymphoma, Leukaemia (all types), Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Chronic lymphocytic leukaemia, Chronic myeloid leukaemia (CML), Diffuse large B-cell lymphoma, Follicular lymphoma, Hodgkin lymphoma, Mantle cell lymphoma, Multiple myeloma, Non-Hodgkin lymphoma (all types), Myelodysplastic syndromes / neoplasms (MDS), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Polycythaemia vera (PV), Essential thrombocythaemia (ET), Waldenström macroglobulinaemia, Hairy cell leukaemia, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Burkitt lymphoma, HIV-associated (AIDS-related) lymphomas, Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Systemic mastocytosis, Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Langerhans cell histiocytosis (LCH), Post-transplant lymphoproliferative disorder (PTLD), FLT3-mutated acute myeloid leukaemia, IDH1- and IDH2-mutated acute myeloid leukaemia, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Secondary and therapy-related acute myeloid leukaemia, Acute promyelocytic leukaemia, Acute myeloid leukaemia in older or unfit patients, Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-eligible, Newly diagnosed multiple myeloma, transplant-ineligible, Relapsed or refractory multiple myeloma, Plasma cell leukaemia, Lower-risk myelodysplastic syndromes, Higher-risk myelodysplastic syndromes, Chronic lymphocytic leukaemia, first treatment, Relapsed or refractory chronic lymphocytic leukaemia, Richter transformation of chronic lymphocytic leukaemia, Chronic myeloid leukaemia, chronic phase, Chronic myeloid leukaemia, accelerated and blast phase, Primary myelofibrosis, Standard-risk B-cell acute lymphoblastic leukaemia in children, High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL), Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL), Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL), Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year), Relapsed and refractory acute lymphoblastic leukaemia in children, Acute myeloid leukaemia in children, Erdheim-Chester disease, Rosai-Dorfman-Destombes disease, Single-system Langerhans cell histiocytosis (bone, skin or one other organ), Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement), Indolent and smouldering systemic mastocytosis, Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia), Advanced-stage classical Hodgkin lymphoma (stage III to IV), Nodular lymphocyte-predominant Hodgkin lymphoma (nodular lymphocyte-predominant B-cell lymphoma), Relapsed and refractory classical Hodgkin lymphoma
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Also on OnCo: Symptoms and red flags · Early detection roadmap.
FDG-PET/CT with Lugano staging; bone marrow biopsy no longer needed when PET is used; fertility counselling and cardiac baseline.
Two cycles of ABVD with 20 Gy involved-site radiotherapy (HD10); or PET-adapted chemotherapy alone (three ABVD if PET-negative after two, RAPID and H10) accepting a small increase in relapse.
Four cycles of ABVD (or two escalated BEACOPP plus two ABVD) with 30 Gy involved-site radiotherapy; radiotherapy omitted in PET-negative patients after HD17.
Response-adapted Children's Oncology Group regimens with radiotherapy for slow responders; AHOD2131 tests brentuximab vedotin with nivolumab.
Cardiac surveillance, breast screening from eight years after chest radiotherapy in women, thyroid checks and second-cancer awareness for life.
GHSG HD10 established the smallest combined-modality treatment that works: two cycles of ABVD followed by 20 Gy involved-field radiotherapy gave five-year freedom from treatment failure of about 93 per cent and overall survival of about 97 per cent, with no advantage from four cycles or from 30 Gy, and fewer acute adverse events at the lower intensity. Four visits of chemotherapy and a fortnight of radiotherapy cure the great majority. Whether the radiotherapy can be dropped in patients whose PET is negative has been asked twice, and both answers were the same. HD16 randomised 1,150 patients: among 628 who were PET-negative after two cycles, five-year progression-free survival was 93.4 per cent with combined-modality treatment against 86.1 per cent with ABVD alone (difference 7.3 percentage points, hazard ratio 1.78), with five-year overall survival of 98.1 and 98.4 per cent. RAPID randomised patients whose PET was negative after three cycles and found three-year progression-free survival of 94.6 per cent with radiotherapy against 90.8 per cent without, with no difference in overall survival and non-inferiority not formally shown. So omitting radiotherapy costs a few percentage points of disease control and costs nothing in survival, while avoiding a field over the heart, breasts, thyroid and lungs in a person who will live another fifty years. It is a genuine choice and it is made differently by different patients and different countries. A Deauville score of 4 on the interim PET predicts a much higher risk of failure than a score of 3, and those patients keep the radiotherapy.
Early-stage disease with risk factors (a large mediastinal mass, extranodal involvement, a raised erythrocyte sedimentation rate, three or four or more nodal areas, or age 50 or over depending on the criteria used) is treated with four cycles of chemotherapy and involved-site radiotherapy at 30 Gy, or with more intensive chemotherapy in place of some of it. EORTC/LYSA/FIL H10 randomised 1,950 patients and settled the PET-adapted question in both directions. In the 18.8 per cent whose PET after two cycles of ABVD was positive, switching to two cycles of escalated BEACOPP with involved-node radiotherapy raised five-year progression-free survival from 77.4 to 90.6 per cent (hazard ratio 0.42). In PET-negative patients, non-inferiority of ABVD alone could not be demonstrated in either the favourable group (99.0 against 87.1 per cent for combined-modality treatment) or the unfavourable group (92.1 against 89.6 per cent), so omitting radiotherapy again costs disease control. Brentuximab vedotin with AVD is an option for unfavourable early-stage disease in some guidelines, and AHOD2131, an international trial in patients aged 5 to 60 with stage I to II disease, is testing response-adapted brentuximab vedotin with nivolumab against standard therapy with or without radiation. That trial is the one most likely to change this row next.
Paediatric protocols differ from adult ones in two ways that matter: they use response-adapted designs to remove radiotherapy from as many children as possible, and they avoid or limit the agents with the worst late effects in a growing body, particularly alkylating agents and chest radiotherapy. Children's Oncology Group and EuroNet protocols give a short course of multi-agent chemotherapy, assess response with PET after two cycles, and give involved-site radiotherapy only to sites that have not responded adequately. The aim is to cure more than 95 per cent of children with the smallest cumulative dose of anthracycline, alkylator and radiation they can be cured with. AHOD1331 showed the direction of travel in high-risk paediatric disease: replacing bleomycin with brentuximab vedotin gave three-year event-free survival of 92.1 per cent against 82.5 per cent (hazard ratio 0.41), with three-year overall survival of 99.3 against 98.5 per cent, similar toxicity and a similar proportion receiving radiotherapy (53.4 against 56.8 per cent). AHOD2131 is now testing brentuximab vedotin with nivolumab against standard therapy in early-stage disease across the ages of 5 to 60, which is unusual and deliberate: adolescents and young adults have historically fallen between paediatric and adult trials and done worse for it. Growth, fertility, thyroid function, cardiac function and psychological support are part of the treatment plan from the first appointment, not the end of it.
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Radiotherapy cannot be omitted in early-stage favourable Hodgkin lymphoma on the basis of a negative interim scan without a clinically relevant loss of tumour control. The scan is better at identifying who needs more than at identifying who needs less.
ECHELON-1 made a targeted antibody-drug conjugate part of first-line Hodgkin therapy and eventually showed that this saves lives, not just relapses. It set the reference arm against which nivolumab-AVD (SWOG S1826) and BrECADD (HD21) were later compared. Neuropathy is the main price and needs proactive dose modification.
The interim scan should be used to intensify treatment in early Hodgkin lymphoma, not to withhold radiotherapy. The 99.0 per cent five-year progression-free survival in the scan-negative favourable group with combined-modality treatment is the number any radiotherapy-sparing strategy has to match.
The reason cardiac surveillance belongs in Hodgkin lymphoma survivorship care, the reason smoking cessation is a specific intervention for this group rather than general advice, and part of the reason modern protocols try to limit both mediastinal radiation and cumulative anthracycline dose.
PET-negative early Hodgkin lymphoma can be treated with chemotherapy alone at a small cost in relapse, an option many younger patients take to avoid radiation to the chest and neck.
The reason every current Hodgkin lymphoma trial is a de-escalation trial, and the reason survivors need lifelong surveillance rather than discharge at five years. It is also a warning about assuming that a gentler protocol is a safer one until a cohort has been followed long enough to say.
Patients with early favourable Hodgkin lymphoma are cured with two cycles of ABVD and 20 Gy of involved-site radiotherapy; later trials tested whether PET can spare radiotherapy altogether.
The dose-response curve behind breast surveillance programmes for women irradiated for Hodgkin lymphoma as teenagers or young adults, which in several countries start at 25 or eight years after radiotherapy and use magnetic resonance imaging as well as mammography.
Query for this cancer: (TITLE:"Early-stage classical Hodgkin lymphoma" OR ABSTRACT:"Early-stage classical Hodgkin lymphoma" OR TITLE:"stage I to II" OR ABSTRACT:"stage I to II" OR TITLE:"Limited-stage Hodgkin lymphoma" OR ABSTRACT:"Limited-stage Hodgkin lymphoma" OR TITLE:"Stage I to II classical Hodgkin lymphoma" OR ABSTRACT:"Stage I to II classical Hodgkin lymphoma" OR TITLE:"Early favourable and early unfavourable Hodgkin lymphoma" OR ABSTRACT:"Early favourable and early unfavourable Hodgkin lymphoma" OR TITLE:"Localised Hodgkin lymphoma" OR ABSTRACT:"Localised Hodgkin lymphoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Early-stage classical Hodgkin lymphoma (stage I to II), not a curated reading list.
The targets of this cancer's medicines and the ones linked to it directly.
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Breathing very fast, confusion or slurred speech, blue, pale or blotchy skin, a very high or very low temperature, shivering, or a rash that does not fade when pressed: the NHS says call 999 or go to A and E, and do not drive yourself.
Any new neurological symptom that is not explained. Brentuximab vedotin carries a boxed warning for progressive multifocal leukoencephalopathy, a brain infection; the label says to hold the drug and investigate at the first suspicion.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Macmillan lists difficulty passing urine, loss of bladder or bowel control and constipation among the signs of spinal cord compression and says to contact the hospital straight away. If you cannot reach anyone, go to A and E and say you have lymphoma and symptoms of spinal cord compression.
These are the signs that the airway or the brain is being affected rather than only the veins. The triage standard sends shortness of breath at rest and any altered level of consciousness straight to 999.
See all on the product pages:BleomycinBrentuximab vedotinCentral venous access (port, PICC line)CyclophosphamideDacarbazineDoxorubicinEtoposideFebrile neutropeniaHypogammaglobulinaemia and infection risk after B-cell therapiesMetastatic spinal cord compression (MSCC)NeutropeniaNivolumabProcarbazineSuperior vena cava obstructionVinblastine·Printable cards in the navigator
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