Blood tests which predict Immune System function and what they mean

Individual medical advice is required to adapt these general comments to your clinical situation. Not all tests are suitable or necessary for every patient. Individual decisions on which tests are appropriate is clearly a matter for medical judgement and will vary depending on your own clinical situation.

We have been told that everyone with blood cancer no matter what stage is immune compromised at least to some degree. COVID-19 has raised our awareness of this. Here in the UK anyone who ever has had a diagnosis of blood cancer were intended to be idetentifed as clinically extremely vulnerable. That was quite a shock to some people. But clearly this vulnerability is not just to COVID19. One reason I am so passionate about this subject is that I was diagnosed with blood cancer during a nasty episode of pneumonia and sepsis, so I was immediately aware of my immune compromise.

But I think we all understand that different patients at different stages of different blood cancers will have different levels of immune function. What can we do to measure that better? And what can we do if we know our immune system is not functioning well? It’s quite strange that even some top blood cancer doctors seem less concerned about the function of our immune system than what our scans and blood tests for the underlying cancer are doing.

The following tests will give some idea of how well your immune system is predicted to function, although oddly some people will have poorly functioning immune systems even with good numbers on these tests and others may have poorly functioning immune systems with good results on these tests.

Ultimately of course the only way to really know how well your immune system works is to get infected with something and see how you handle it. But clearly in some cases that may not be a particularly safe way of finding out.

Crucially in some blood cancer patients with poor immune function colds and flus appear less severe than normal. But this may not be a sign the immune system is working well, quite the opposite. Many of the symptoms of infection including fever, mucus production, inflammation, and certain blood marker changes are all actually the work of our immune system fighting off the alien invader. So having only mild (but perhaps longer lasting) colds might actually be a warning sign that you are more vulnerable than you realise.

As the next best test of your immune function, receiving a vaccine followed by an antibody level test is a safe and clear measure of how well your immune system is likely to react to a new illness.

If you don’t respond to the COVID vaccine you may want to discuss with your doctors having at least some of the following tests.

Full blood count (FBC or CBC) to assess the level of your total lymphocytes and neutrophils.

This test is crucial and any significant change in any symptoms that might suggest infection should trigger an urgent request, even if only for reassurance. The numbers of the various different types of cells can sometimes change quite quickly, and any doctor you see with new symptoms that concern you may well want want to do an up to date full blood count (also called Complete Blood Count or CBC)
- Focus on absolute counts ignore percentages except to calculate absolutes if not given in the report. (Total WBC multiplied by the % cell type divided by 100 = absolute count).
- Anything less than 1 (thousand) of either of the main types of white blood cell is low enough to consider possibility of some kind of intervention.
High neutrophils often indicate an infection. Sometimes however if your bone marrow is struggling to make enough as they are used up the level may not increase sufficiently during an infection in blood cancer patients. It may even drop instead.
Neutrophils can sometimes reduce suddenly at any stage of blood cancer, and particularly during treatment (including with the newer selective treatments).
Low neutrophils plus a temperature requires immediate treatment in an ER or A and E as a medical emergency. Doctors will act on the assumption you are suffering from neutropenic sepsis which can deteriorate rapidly, even though of course this may well not be the case. You may be treated with a very strong antibiotic whilst waiting for blood results. The good news is that such treatment if given early is very effective.
In fact ANY blood cancer patient at any stage with a fever of over 38C or 100.4F would benefit from an ER / A and E / urgent care visit for immediate FBC inflammatory markers, and infection screen (including Chest x-ray if indicated).
- Inform reception you are immune compromised, and need to have neutropenic sepsis ruled out. Since neutrophils can sometimes suddenly drop even without treatment.
- Note that even in the middle of chemotherapy a temperature may often indicate something much more common like a cold or flu, but ruling out more serious causes is sensible and reassuring.
- Doctors often advise their blood cancer patients to avoid paracetamol/ acetaminophen, ibrupropfen and other NSAIDS to avoid the risk of “masking” a fever and therefore delaying seeking help.
- Early antibiotics can prevent deterioration after an initially mild infection, so even lower fevers should be discussed with your medical team.
Neutrophil production can be increased by CGSF injections and/or a pause in anti-cancer treatment
Low lymphocytes after treatment are an indicator that you may not be able to make antibodies to infections your body has not seen before. A cut of of below 1(thousand) is often used as an indicator you should be on prophylactic medicines (See below under lymphocyte subtypes). Note that a low lymphocyte count also seems to be almost a necessary factor associated with gettting to the undetecable cancer cells status (often referred to as MRDU) of a deep full remission which can lead to very long treatment free periods. When I have an FBC these days I never know whether to be happy or sad that my lymphocyte count is so low. Mostly happy since at this point I suspect any recovery in the count is likely to be cancer cells rather than healthy lymphocytes as 2 years after finishing chemo there is still no sign of healthy lymphocytes returning. Many people will see a recovery in their healthy lymphocytes after treatment. I haven’t.

Flow cytometry on the blood to assess what percentage of your lymphocytes are healthy.

This would be most relevant if you have CLL or certain other types of lymphocyte blood cancer.
If your lymphocyte count was say 50 (thousand) but 99% are CLL cells, your healthy lymphocytes would be low at 0.5 (500) and you would effectively be lymphopenic (which just means low lymphocytes).
More information: UK, USA (includes CPT code)

Lymphocyte sub-types to assess the level of your CD4 T cells.

It is possible these could be low even if your total lymphocytes are high.
- Note that this is not the same as measuring the level of specific T cells created in response to the COVID19 spike protein. That is currently an experimental test and unlikely to be available outside clinical trials, although one such test can be purchased in the USA. It seems that the likelihood of such a response having occurred is presumably lower if the T cell count is low, however.
- If CD4 T cell Levels below 0.2 (200) or 14% then most experts advice that we should start prophylaxis with Co-trimoxazole (=Bactrim, Septrim) or alternative. This is also usually started at the beginning of any blood cancer treatment to cover the possibility that T cells may drop. In addition aciclovir or a related drug will likely be added to prevent shingles and other herpes viruses from being reactivated in the absence of T lymphocytes. Note that patients in this group are particularly vulbarable to all viruses including COVID19 and so some form of social distancing and mask wearing may be indicated. I made a decision when I was first diagnosed with this not to travel on crowded public transport. Others might decide to do so but wear a good quality N95 or N99 respirator. I have a pack of disposables designed fo use during DIY activities which has a rubber seal improving the airtighness of the mask which I use if I have to go into areas where there are other people especially indoors. (Eg when I attend a medical appointment I will probably always wear a mask from now on even when COVID-19 is over. )
- If total lymphocyte count is below 1 (1000) many doctors will simply assume the CD4 T cell count will be below the cut off and treat accordingly.
- More information: UK, USA

Blood antibody level – focus on IgG levels.

Other types of antibodies are also measured but the results are usually not relevant for treatment decisions.
Low IgG levels are an indication for consideration of possible IVIG / SCIG treatment an immunologist may be best placed to assess this. Anything less than 5.5 (or 550) has been shown to predict that you are less likely to make antibodies to a COVID19 vaccine and presumably others.
But obtaining funding for treatment with IVIG/SCIG can be difficult and often requires some of the following conditions: an IGG level of less than 4 (or 400), failure to respond to a vaccine trial by making antibodies (see below), regular infections despite the use of prophylactic antibiotics (often azithromycin). Some patients have to really campaign to get access to this including putting in formal complaints or asking for a second opinion wirh an immunologist. Immunologists are also more likely to offer the subcutaneous route which is much more convenient as you learn to give it to yourself at home and is associated with far fewer side effects than IVIG which can prompt severe symptoms some even requiring hospitalisations. It is scandalous that patients who choose to be treated only by their haematologist are placed at greater risk of things like aseptic meningitis (when you have all the symptoms of a secere brain infection and so are rushed to Hosptal and only after lumbar punctures can you confirm that in fact this is a drug side effect which will safely pass).
Bizarrely having said all that some people produce almost no antibodies to anything but still don’t seem to get any infections at all which is really weird!

Specific antibody levels for various diseases

A number of different tests for specific antibodies are available. Among the most important are pneumonia antibodies which can assess how well your pneumonia vaccine worked even it it was given a few years ago.
Your doctor may also want to give you a different test vaccine (followed by antibody levels) to confirm that you are not responding to any vaccines. I was given the Typhoid vaccine to help assess my immune system. I failed to produce a single antibody and this lead to them agreeing to treat me with IVIG.
Proof that your body is not responding well to vaccines is one of the main indicators that you may need IVIG/SCIG.

Treatments to support your immune system

Sadly many of us are sitting on poorly functioning immune systems and don’t know it until we get pneumonia. It may be better to anticipate this.

I have a personal theory, and it is just that at this stage, but it is possible that we may see benefits if we monitored our immune function in patients on watch and wait. Could it be that being treated before there were too many signs it had deteriorated too much our immune system might recover better after treatment? This is not proven as far as I know and I am not even aware currently of any publications which track immune function tests in patients with blood cancers as they progress.

Some of us need IVIG/SCIG (antibody replacement) even before treatment to have better functioning immune systems. Do not assume at this stage that will protect against COVID19 yet. If you meet the criteria it is worth pushing to be considered for this.

There’s a real injustice that patients seeing immunologists are more likely to get treated with IVIG/SCIG than those seeing most blood Cancer doctors. Some Doctors seem to make up rules that don’t even exist for example claiming that you have to have regular hospitalisations for infection when you actually just have to have regular infections. Since s hospitalisation is a potentially life threatening even we should look for early warning signs rather than shutting the stable door after the horse has bolted.

Many doctors also don’t actually ask their patients if they have had infections, don’t check IGG levels routinely, and don’t appropriately offer antibiotic prophylaxis (one of the things you are meant to try first) and don’t routinely check the response to vaccines even though that’s another reason to give it. This is crucial as we might have a relatively not that bad IGG level but be unable to make new antibodies due to poor B cell function.

Much of the IGG comes from the memory cells making antibodies to old infections and these cells are not damaged by most blood cancer treatments. If you do not have healthy B lymphocytes, however, as plasma cells die naturally they will not be replaced hence why many patients, especially with CLL, will see a gradual decline in antibody levels the longer they have the disease whether treated or not.

I really do think experts need to come up with a proper consensus statement on managing infectious disease risk for all blood cancer patients in the post COVID19 world..

In the meantime, other practical methods to reduce the risk of any infections are becoming more widely understood thanks to COVID19 and some modified form of social distancing and mask wearing in certain circumstances may continue to be wise for many blood cancer patients even after the pandemic. We do need to balance the risks and benefits of social contact, however, and living in a bubble forever is clearly not necessary for most of us nor desirable.

Hopefully the background infection rate of COVID19 will plummet soon in countries that are vaccinating rapidly, and we will then be safe. Till then it’s continue to shield I guess even if the official shielding is lifted.

AZ is currently developing its Monoclonal antibody cocktail for COVID19. If this is successful it is most likely to be available to those with a documented COVID19 vaccine failure. Another reason to get that antibody test done.

If you get regular bacterial infections, prophylactic antibiotics (often azithromycin) may be indicated. Discuss this with your doctor for specific advice.

In summary we need to do our best to protect ourselves against catching infections in the first place, and ensure you reach out early for antibiotics at first sign of infection, attending ER / A and E if severe fever (over 38C / 100.4F)