Lymphoma Treatment

Six years after treatment for advanced Hodgkin lymphoma, 93.9 percent of patients in a recent trial were alive. For some slow-growing lymphomas, the best first treatment is none at all.

Both statements rest on randomized trials. The first comes from ECHELON-1, in which 1,334 patients with stage III or IV Hodgkin lymphoma received one of two drug combinations (Ansell and colleagues, New England Journal of Medicine, 2022). The second comes from a British trial that followed 309 people with advanced, symptom-free, low-grade lymphoma for a median of 16 years and found that those who were simply observed lived as long as those treated at once (Ardeshna and colleagues, The Lancet, 2003). Lymphoma treatment spans that whole range, from watchful waiting to intensive chemotherapy, because lymphoma is a family of more than sixty diseases. This page sets out how the type is established, what treatment each main type receives, what side effects to expect, what happens at relapse, and how patients from abroad can be assessed and treated at Biruni Hospital in Istanbul.

Lymphoma is many diseases

Lymphoma means cancer of lymphocytes, the white blood cells that live in lymph nodes, spleen, marrow and the lining of the gut. The word covers conditions as different from one another as a cold and pneumonia.

Two facts decide treatment more than any others. The exact type under the microscope, and whether that type grows fast or slowly.

Hodgkin and non-Hodgkin

Hodgkin lymphoma, recognized by a distinctive giant cell, affects mainly young adults and is among the most curable cancers. Doctors group everything else as non-Hodgkin lymphoma and divide it into aggressive types, which grow over weeks and are treated at once with the aim of cure, and indolent types, which grow over years, respond well to treatment, tend to return, and are managed more like a chronic illness.

Before treatment starts

A week or two spent on a complete workup is time well used, except in the fastest lymphomas. The standard elements are these.

• A surgical or core needle biopsy of a lymph node, read by a pathologist with lymphoma experience. Fine needle samples are not enough.
• PET-CT from skull base to thigh, which maps every active site.
• Blood count, kidney and liver tests, LDH, and tests for hepatitis B, hepatitis C and HIV.
• Bone marrow biopsy in selected types.
• Echocardiography before drugs that can affect the heart.
• A conversation about fertility, before the first dose.

Why stage IV is not what it sounds like

Lymphocytes travel through the whole body by nature, so lymphoma tends to be widespread at diagnosis. Drug treatment reaches it wherever it lies. Cure at stage IV happens regularly. Doctors add the letter B when fever, drenching night sweats or loss of more than a tenth of body weight are present, and they combine stage with age, blood results and fitness into a risk score that guides the choice of treatment.

First treatment

Diffuse large B-cell lymphoma

Treatment rests on R-CHOP, four chemotherapy drugs plus the antibody rituximab, which attaches to a protein called CD20 on B cells. A French trial in 399 patients aged 60 to 80 settled its value. Complete responses rose from 63 to 76 percent when rituximab was added, the risk of death fell by a third, and side effects were not meaningfully worse (Coiffier and colleagues, New England Journal of Medicine, 2002). A newer version that replaces one drug with an antibody-drug conjugate is used for some higher-risk patients. A course runs as follows.

1. Day 1 of each cycle. Antibody and chemotherapy by drip in the day unit, over four to six hours. The first antibody infusion runs slowly to watch for reactions.
2. Days 1 to 5. Steroid tablets at home.
3. Days 7 to 14. White cells reach their lowest. A growth factor injection shortens this period for many patients.
4. Day 21. Blood test, clinic review, and the next cycle. Six cycles take four months.

Hodgkin lymphoma

Early-stage disease receives two to four cycles of ABVD. A short course of radiotherapy follows in many cases. Advanced disease receives six cycles, and the interim PET-CT is used to lighten or intensify treatment. In ECHELON-1, replacing bleomycin with the antibody-drug conjugate brentuximab vedotin raised overall survival at six years from 89.4 to 93.9 percent, with fewer second cancers and more nerve tingling, which improved with time in most patients.

Slow-growing lymphoma and watchful waiting

Doctors treat indolent lymphomas when they cause trouble. Until then, treatment adds side effects without adding years. Doctors start when one or more of the following appears.

In the British trial, median survival was 5.9 years with immediate chlorambucil and 6.7 years with observation, a difference that was not significant. Ten years on, 19 percent of the observed patients had still needed no chemotherapy, and 40 percent of those older than 70.

Radiotherapy

How it is given

Biruni Hospital delivers radiotherapy on an Elekta Versa HD linear accelerator. Chemotherapy takes place on the same site. One team coordinates both parts of a combined plan.

Very low doses for indolent lymphoma

Follicular and marginal zone lymphomas shrink in most cases after only two small sessions on consecutive days, with almost no side effects. Doctors use this to relieve a troublesome mass without starting drug treatment.

Side effects and staying well

During chemotherapy

Life between cycles stays close to normal for the majority. The effects below are the common ones, and nearly all can be prevented or eased.

Infections and vaccines

Rituximab lowers antibody responses for a year or more. Inactivated vaccines, including influenza, are best given before treatment where time permits. Live vaccines are avoided. Anyone who has ever had hepatitis B receives a protective antiviral throughout treatment and for at least a year afterward, because the virus, silent for decades in the liver, reawakens when B cells are wiped out and has caused fatal hepatitis in patients whose lymphoma was responding perfectly well.

If lymphoma comes back

Second-line options

For aggressive B-cell lymphoma and Hodgkin lymphoma that return and respond to a different chemotherapy, high-dose treatment with an autologous stem cell transplant is the established route to cure. Timing matters. Large B-cell lymphoma that returns within a year of first treatment responds poorly to that route, and randomized trials have moved such patients toward CAR T-cell therapy where it can be obtained. Hodgkin lymphoma has two further effective drug classes, brentuximab vedotin and the checkpoint inhibitors, and indolent and mantle cell lymphomas have targeted tablets that are taken daily at home for as long as they work. Transplant from a donor remains in reserve for younger patients whose lymphoma has returned after an autologous transplant. Clinical trials deserve a question at every relapse, since several of the drugs described on this page were available only in trials five years ago, and the patients who entered those trials received them first.

Bispecific antibodies, given as injections or drips, bring the patient's own T cells into contact with lymphoma cells. They have produced lasting remissions after several earlier treatments had failed.

Follow-up and life afterward

Most relapses of aggressive lymphoma occur within the first two years. After five years in remission they are uncommon.

The schedule

Visits come every three months for two years. They then fall to every six months until year five, and to once a year after that. Each includes a conversation, an examination and blood tests. Routine scans in people who feel well have not been shown to improve survival and are kept to a minimum.

Report a new lump, drenching sweats, unexplained fever, itching or weight loss without waiting for the next appointment.

Getting back to normal

Energy returns over three to six months. Many people find the months after treatment harder emotionally than the treatment itself, when the appointments stop and the worry does not, and that reaction is common enough to be considered normal. Exercise helps. So does a clear written summary of what was given, in cumulative doses, which every survivor should keep for life and show to any new doctor.

Coming from abroad

Send the pathology report, the PET-CT report with images, blood results and a list of any treatment already received. Hematologists review the file without charge. If the biopsy material is limited or the type uncertain, they will ask for the paraffin block or slides to be sent for a second reading, which changes the diagnosis in lymphoma frequently enough to justify the courier fee. The written reply states the proposed treatment, the number of cycles and the length of stay. Six cycles at three-week intervals mean either four and a half months in Istanbul or a shared plan, in which the first cycle and the scans are done here and the cycles between are given by a hematologist in your own country to the same protocol. Both arrangements work. You are fit to fly between cycles once blood counts have recovered, which happens in the third week, and the doctor confirms each time.

One coordinator from the international patients office handles arrangements from the first message through discharge, and the same WhatsApp number answers once you are back home. The office works in English, Arabic, French, Russian, Serbian, Romanian and Spanish and books interpreters for other languages. It arranges the visa invitation letter, airport transfers, daily transport and accommodation near the hospital. Ward rooms have a companion bed. The kitchen prepares halal, vegetarian and diabetic meals. A prayer room is on site, and a request for a female physician is met wherever the rota allows.

Cost

The estimate follows the file review and is built from the workup, the number of cycles, the drugs in the regimen and any radiotherapy. Antibodies and newer targeted drugs account for most of the variation between plans.

Hospitals in this market quote per cycle and per radiotherapy course.

Confirm what each figure includes.