Donor lymphocyte infusion (DLI)

What is a donor lymphocyte infusion?

A donor lymphocyte infusion (DLI) is when doctors collect T cells from a donor and deliver them into your bloodstream through a process called ‘infusion’.

These T cells are a type of white blood cell called ‘lymphocytes’ that can:

• cause an immune response
• fight infection.

The process of infusion means putting a fluid into your veins, which in this case means giving you the T cells from a syringe.

Why would I get a DLI?

You might get a DLI if you have a sibling or matched unrelated donor (MUD) stem cell transplant. That said, not everyone who has either of these types of transplant will need a DLI.

There are two main reasons why your medical team might need to give you a DLI.

DLI for mixed chimerism

After a stem cell transplant, doctors regularly measure your chimerism level. This tells them the ratio of stem cells from your donor versus from your own cells. Ideally, your chimerism should be as near as possible to 100% donor cells.

If your chimerism level stays consistently low or keeps dropping, it means you don’t have enough donor stem cells in your body. In this case, you might risk relapse or graft failure. Doctors might give you a DLI to cause an immune response which can push the chimerism up to an acceptable level.

It’s important to remember:

• Not everyone will achieve 100% donor chimerism. However, this is completely fine as long as it remains stable during recovery.
• Doctors will need to monitor your chimerism over a period of time before deciding to offer you a DLI.
• If your chimerism drops, it does not necessarily mean you’ve relapsed.

DLI for relapse

Doctors can give you a DLI to treat relapse after stem cell transplant. Relapse is when your original blood cancer or blood disorder returns after treatment.

However, depending on the strength of the relapse, doctors might treat you using a DLI in slightly different ways:

• For a low-level relapse that doctors have picked up early in a test for minimal residual disease (MRD), the immune response caused by a DLI can fight the blood cancer or disorder you had and help put you into remission. Being in remission means there is no longer any evidence of the disease you had in your body.
• In comparison, if doctors pick up signs of relapse on a blood or bone marrow test with a higher level of the blood cancer or disorder you had, doctors will use chemotherapy followed by a DLI to help put you into remission.

It’s important to remember:

• it’s not always possible to use a DLI as treatment for relapse
• relapse can occur either with or without a drop in chimerism.

If your blood cancer or disorder has a known higher risk of relapse after transplant, doctors might plan a DLI for you in the pre-transplant phase, which they’ll give you after transplant. In this case, it doesn’t take into account potential mixed chimerism or relapse – it’s an extra measure to help prevent relapse. Doctors should discuss this with you before your stem cell transplant.

How do doctors collect DLI cells?

When doctors collect the donor’s lymphocyte cells for a DLI, they can do it at the same time as collecting stem cells for transplant. It will however depend on the volume of cells collected:

• If there are enough lymphocytes within the collection, then doctors can remove, freeze and store cells for a DLI to use at a later date.
• If there aren’t enough, and doctors need to use the entire collection for the transplant, your team will contact your donor and ask them to donate more cells later for the DLI.

A DLI alone is easier to collect than stem cells – the procedure doesn’t involve G-CSF injections as high levels of lymphocytes are always present in the blood. However, the donor will still need to agree and have a medical examination before going ahead.

How do doctors give a DLI?

Doctors will thaw the frozen DLI and give it to you through a syringe into your bloodstream – it’s given in much smaller volumes than stem cell transplants. When it’s thawed, some people occasionally experience a smell like sweetcorn in the air. This comes from a preservative called ‘DMSO’ which doctors add when freezing the DLI.

In most cases, you get a DLI as an outpatient in hospital. But if you need chemotherapy as an inpatient beforehand, then you’ll also get the DLI as an inpatient.

You normally get a DLI in increasing doses over a period of weeks or sometimes months. Your transplant team will decide on the best timing and dose for you.

What are the side effects of a DLI?

Generally, it’s rare to experience side effects from a DLI. A nurse will be with you throughout the whole infusion and will observe you for a short time after.

The main potential side effect is graft versus host disease (GvHD). This can happen in the weeks following your infusion. While it’s not a pleasant side effect, GvHD can be a positive response – it suggests the DLI has caused an immune response, which is the aim.

The key is to balance GvHD by not causing too much of a reaction, but enough to achieve the aim of a DLI. Getting the DLI in increasing doses over a period of weeks is a way of controlling the risk.

If you don’t get GvHD, that does not mean the DLI hasn’t worked – you can achieve an immune response without any side effects.

Why would doctors not give a DLI?

As everyone has a different experience of stem cell transplant, your own medical team will make the decision on whether to give a DLI. You should always discuss treatment with your transplant consultant, but they might not give a DLI for reasons such as:

When a second transplant is the best treatment option

Doctors will only consider a second transplant in the case of relapse or graft failure. Several factors go into this decision, including the level of relapse or graft failure, time since transplant, age and fitness. Your transplant team will discuss this with you.

If you’ve already experienced significant acute GvHD

Acute GvHD usually starts within 100 days of your transplant. Generally this means the donor stem cells have caused a good immune response. However, if your chimerism has continued to drop or you have relapsed, then giving a DLI to try and cause more GvHD is unlikely to work. You’ll need to discuss this with your transplant team, as low levels of acute GvHD could still mean that a DLI is an option.

If you’re having ongoing treatment for chronic GvHD

Chronic GvHD usually starts more than 100 days after your transplant. If you get a DLI while you have chronic GvHD, as well as while having treatment for it, this can cause your symptoms to worsen. Like in acute GvHD, if you’ve already been experiencing chronic GvHD, a DLI is unlikely to work.

Recovering from a DLI

Your recovery will vary depending on your experience of GvHD. At first, you might have regular follow-up appointments in hospitals or clinics to allow doctors to monitor you for symptoms and response, and to decide if you need another DLI.

If your DLI treatments achieve the immune response and manage to resolve any GvHD, your recovery should continue as it was before your first DLI.