Spotlight on steroids in the treatment of lymphoma

We asked Natalia Czub, Advanced Haematology Pharmacist at Oxford University Hospital to answer some of the questions we are asked about steroids.

Are the steroids used for lymphoma the same as those we hear about in connection with being performance enhancing?

The simple answer is no, they are not the same. The steroids used in the treatment of lymphoma, such as glucocorticosteroids (for example, prednisolone , dexamethasone or methylprednisolone) are mainly used for their abilities to reduce inflammation, suppress your immune system, and to destroy cancer cells.

They are different from the anabolic steroids you may have heard about in connection with performance. Anabolic steroids are manmade (synthetic) variations of testosterone and are used to promote muscle growth and enhance physical performance. These steroids can have significant side effects and are banned in most sports.

How do steroids work?

Steroids used in lymphoma mimic the actions of steroids that are produced by the adrenal glands in the body. They reduce inflammation and immune responses. They are toxic to lymphocytes and work by directly killing the cancer cells. When used in combination with chemotherapy (for example in regimens, like R-CHOP) they can enhance the effectiveness and reduce the side effects of chemotherapy like infusion-related reactions and nausea and vomiting. They can also reduce side effects of other treatments such as cytokine release syndrome or neurotoxicity related to CAR-T cell or bispecific antibody therapies. Steroids can also be used to increase appetite and boost energy levels.

Steroids work by binding to the receptors inside cells, called nuclear receptors. Once attached to the receptor, they enter the cell nucleus which is the controller of the cell. Here they can cause the cell to produce more anti-inflammatory proteins or suppress genes that promote inflammation. By interfering with DNA synthesis in this way, steroids can also affect production of the malignant cells. The mechanism is complex and involves multiple signaling pathways, leading to the programmed cell death (apoptosis), which is crucial for reducing the number of malignant cells.

Are they always given in tablet form?

Steroids used in lymphoma are mainly given orally as tablets or liquids or into the vein (intravenously). They can also be given as an injection into the muscle (intramuscular) or spine (intrathecal), or topically, as creams or ointments.

Is there a standard dose for everyone?

Steroid dose will depend on the individual person’s condition, lymphoma type and clinical context, considering the potential side effects, so will not be the same for everyone. The initial dose is often higher than the maintenance dose as the main aim is to initiate symptoms management and reduce inflammation. The dose is then gradually reduced to a lower maintenance level to balance symptom control with minimising side effects.

Why do steroids increase your appetite and often cause people to gain weight and sometimes even change their appearance?

Steroids can increase appetite by:

• altering brain signals related to feeling full and satiety
• increasing cravings for calorie-dense foods, leading to overeating.

Steroids can lead to weight gain due to:

• fluid retention and redistribution of fat
• increased calorie intake because of an increased appetite
• reduced breakdown of muscle protein.

Steroids can sometimes cause changes to appearance:

• Moon face: swelling of the face due to fluid retention.
• Buffalo hump: fat accumulation at the base of the neck.
• Weight gain: especially in the abdomen and face.
• Stretch marks: due to skin thinning.
• Acne: increased oil production.
• Thinning skin: fragile skin prone to bruising.

Will steroids affect my mood?

Yes, steroids can indeed affect mood. Examples can include:

• Euphoria and irritability: some people experience increased energy, euphoria, or irritability due to steroid use.
• Mood swings: steroids can lead to mood fluctuations, including anxiety, depression, and even aggression.
• Psychiatric effects: rarely, severe psychiatric effects like psychosis or mania may occur.

Abruptly stopping steroids can also cause mood changes and withdrawal symptoms.

How long can I expect to be taking the steroids for?

The duration of steroid treatment, like the dose, will be tailored by the lymphoma specialist based on the individual patient’s clinical needs and tolerance. High doses of steroids are given initially to manage symptoms and reduce inflammation for a few days or up to a few weeks. The duration of maintenance treatment varies but can extend for several months.

Why do I need to declare I am on steroids if I’m having any other treatments (such as dentistry)?

This is particularly important as steroids, especially when taken for a longer duration of time, can increase the risk of adrenal crisis, where the adrenal glands’ natural production of cortisol is suppressed. If you suddenly stop taking steroids or experience major stress (such as illness or surgery), your body may not produce enough cortisol, leading to an adrenal crisis. An adrenal crisis is a medical emergency that can be fatal if left untreated. Steroid Treatment Cards should be issued where appropriate to support communication of the risks associated with treatment and to record details of the drug, dosage, and duration of treatment. Dentists and other healthcare providers need to be aware of your steroid use to adjust treatment plans. Steroids can affect wound healing, immune response, and stress management during dental procedures.

Steroid Emergency Card: People with adrenal insufficiency (primary or secondary) should carry a Steroid Emergency Card, which helps healthcare staff recognize adrenal insufficiency and provides emergency treatment guidance. It ensures timely administration of higher steroid doses during acute illness or stress.

I’ve heard there are dangers of coming off steroids. Why does this happen?

It is important to follow the advice given by your medical team when finishing steroid treatment because:

• Abruptly stopping steroids can lead to adrenal insufficiency, causing symptoms like extreme fatigue, weakness, dizziness, poor appetite, weight loss, and gastrointestinal issues.
• Your original symptoms might return suddenly - gradual tapering helps prevent this rebound effect.
• Prolonged steroid use can lead to side effects such as weight gain, fluid retention, difficulty sleeping, mood and behaviour changes, high blood sugar, gastric irritation, muscle weakness, osteoporosis, and a condition called Cushing’s syndrome.

If you would like a list of references supporting this article, email publications@lymphoma-action.org.uk