Classic Hodgkin lymphoma

It is a cancer of the lymphatic system — the network of nodes and vessels that carries immune cells around the body — and it usually starts in nodes above the diaphragm: the neck, the armpit, the chest.

It is defined by a particular abnormal cell, large and often with more than one nucleus, called a Reed-Sternberg cell. And here is the strange and important part: those cancer cells are only about 1% to 10% of the tumour. The other 90% or more is ordinary immune cells that the cancer has recruited and reprogrammed to support it rather than kill it.

That is why diagnosing it usually means removing a whole lymph node rather than taking a needle sample. There is not enough cancer in any small piece to be sure.

Two things are worth separating out. Classic Hodgkin lymphoma has four subtypes, but treatment is decided by stage and risk group rather than by subtype. And nodular lymphocyte-predominant Hodgkin lymphoma is a genuinely different disease with the opposite pattern of cell markers — nothing on this page should be read across to it.

The NCI lists risk factors rather than causes: being a young adult or over 65, being male, having had Epstein-Barr virus in childhood or the teenage years, and having a first-degree relative with it.

Epstein-Barr virus is associated with a substantial minority of cases — around 40% in Western countries in one review — but it is extremely common in the general population and the overwhelming majority of people who have had it never develop Hodgkin lymphoma. Association is not causation, and there is no preventable individual exposure here.

One genetic change matters a great deal for treatment. Most classic Hodgkin lymphoma has extra copies of a region of chromosome 9 that carries the genes for PD-L1 — a molecule the tumour displays to switch off attacking T cells. That is why checkpoint-inhibitor drugs, which release that brake, work unusually well in this specific cancer.

Nothing in these sources supports a lifestyle, diet, stress or injury cause.

The commonest first sign is a painless swollen lymph node in the neck, armpit or groin.

Beyond that: fever, drenching recurrent night sweats, unexplained weight loss, fatigue, and itching — sometimes notably after a bath or after drinking alcohol. None of these is specific, and all of them have far more common explanations.

Because it usually starts above the diaphragm, a large mass in the chest is common.

About half of people present with limited-stage disease and about half with advanced. Advanced stage at diagnosis is not the same thing as a poor outlook in this disease — even at the top of the risk score used for advanced disease, the NCI reports five-year survival above 70%.

Roughly a fifth to a quarter of people do not respond to first-line chemotherapy, and that is the group in which the disease behaves most aggressively and the group most likely to be routed toward a transplant.

The headline is that classic Hodgkin lymphoma is usually treated with drug therapy, sometimes with radiotherapy, and most people never have a transplant of any kind. The NCI states that up to 90% of newly diagnosed patients can be cured with combination chemotherapy and/or radiotherapy — that is a stated ceiling in a summary rather than a measured outcome or a promise.

Early-stage disease is treated with a few cycles of chemotherapy, sometimes with radiotherapy to the affected area. Which combination and how many cycles depends on whether adverse features are present.

Advanced-stage first-line treatment changed recently. The NCI now describes nivolumab combined with three chemotherapy drugs as the standard approach, replacing a regimen that had stood for three decades, on the strength of a trial in 994 patients where two-year progression-free survival was 92% against 83%. The FDA approved that combination in March 2026. The older regimen has not disappeared and remains a reasonable and cost-effective option where the newer one is unaffordable.

Treatment is increasingly response-adapted, meaning the plan changes based on a scan after the first two cycles. That can mean dropping a drug to avoid lung toxicity, or omitting radiotherapy — though the evidence there is a genuine trade-off rather than a settled answer, with fewer relapses when radiotherapy is given and no clear survival difference.

When a transplant is used at all it comes after relapse or refractory disease, not at diagnosis, and it is normally autologous — the person’s own cells collected beforehand and given back after high-dose chemotherapy.

Checkpoint inhibitors and brentuximab vedotin have changed transplant’s role in two directions at once. They are used to get someone into remission before a transplant — and they are also used instead of one, particularly for older people or those for whom a transplant would be too much.

Diagnosis usually means having a whole lymph node removed surgically, then scans of the chest, abdomen and pelvis. A marrow biopsy is now generally avoided.

Treatment is months of intravenous cycles, sometimes followed by a few weeks of radiotherapy. One thing people are often not told: the symptoms of the lymphoma itself frequently improve within days of starting.

Because the disease peaks in the twenties and thirties, treatment lands in the middle of education, early careers, new relationships and family planning. Fertility counselling has to happen before treatment starts rather than after — and which regimen someone receives matters for that, since they differ substantially in their effect on fertility.

And then survivorship, which for a young person means decades. Second cancers, heart and lung effects, and thyroid problems are all recognised, and follow-up continues long after treatment ends.

Most people with classic Hodgkin lymphoma never need a transplant at all, and most of those who do receive their own cells. A Hodgkin diagnosis is not, on its own, a reason to look for a donor.

The distinction is worth being exact about. An autologous transplant collects and freezes the person’s own blood stem cells before high-dose chemotherapy, then gives them back to rebuild the marrow. There is no donor, no registry search, no tissue matching and no graft-versus-host disease. It is a rescue from the chemotherapy rather than a transfer of someone else’s immune system.

An allogeneic transplant uses cells from another person, and it is the only setting where a registry donor comes into it. The NCI places it after salvage therapy in disease that never responded — behind checkpoint inhibitors, brentuximab vedotin and autologous transplant in the sequence, not ahead of them. Its stated trade-off is that a matched sibling transplant lowers relapse but the benefit may be offset by increased toxicity.

And honestly: joining a registry does not help a specific person with Hodgkin lymphoma, and Hodgkin lymphoma is a small part of unrelated-donor demand. The people most likely to need an unrelated donor have leukemias, myelodysplastic neoplasms and some inherited marrow disorders.