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High risk for Blood Cancer patients with COVID19

This post has the latest data which demonstrates the high risk for complications from COVID-19 of all patients with blood cancer. It is quite discouraging reading, so not everyone will want to read the data. But there are seeds of hope for us in the Coronavirus Hope series of which this is a part. If you need a more uplifting read try one of the following:

The essense of the problem is that blood cancer is a cancer of the immune sytem. Even before treatment many blood cancers are associated with a reduction in the ability of the body to fight infections, including producing antibodies. Often healthy lymphocytes are weakened or crowded out by the cancer and so even before treatment people with a lymphocyte blood cancer are at a unique disadvantage to others in facing covid 19.

No current blood cancer treatment can distinguish bewtween healthy lymphocytes and the blood cancer cells. So treatment turns our bodies against not just the cancerous lymphocytes but the healthy ones too. And so we hugely impair our ability to find new antibodies. This impairment can last many years even if patients are in remission.

To use an ilustration, it’s like going into battle with not just both hands tied behind the back and a blindfold on, but with the weapons factories disabled too. As a result blood cancer patients are uniquely vulnerable to this cursed disease. Despite shielding the data below shows clearly that we are at high risk.

If you have blood cancer it is safest to avoid catching COVID-19

UPDATE 13 July 2020

There are now five separate data sets that have been reported a death rate of 40% in patients with symptomatic COVD19 and blood cancer. Having proven that it is possible to catch a rhinovirus whilst strictly shielding I urge you to continue to be vigilant (e.g. use gloves to handle delivered shopping, etc). Keep safe. Here are the three datasets

  • Bart’s patient series (40% death rate)
  • King’s patient series (40% death rate)
  • ASH patient series (30% death rate)
  • European patient series
  • “At last follow-up 20 patients (34%) died due to COVID-19. The mortality rate for patients above 60 years was 45%, and that for patients below 60 years was 11%. There was no difference in survival between lymphoid and myeloid malignancies. In addition, we did not observe any difference in survival between the different treatment strategies of COVID-19 infection.”
  • EU (ERIC) study of 190 CLL patients with COVID-19
    • 56 of these patients died, a rate of 29%.
    • 89% of the patients needed hospitalisation
    • 79% of the overall total had severe COVID19 i.e. needed oxygen or ITU admission. All but one of the deaths were in this group (36% death rate).
    • However 11% of the total group of patients had relatively mild disease and were managed at home.
    • Twice as many men than women presented with COVID19
    • 76% of CLL patients with COVID19 also had other diagnoses – the most common being high blood pressure.
    • 38% of presenting COVID19 patients had never been treated for their CLL.
    • A comparison was made between the severe and mild patients. The following did not seem to predict the presence of severe disease: gender, having three or more other diagnosis, or the presence of hypogammaglobulinemia. However older age predicted severity with 74% in the severe group being 65 years or over compared to only 44% in the less severe.
    • Death rates were not significantly different between age groups with the young with CLL being at a similar risk of death as the old.
    • Rather suprisingly 60.3% of the severely ill patients had never had treatment or had been off treatment for the past year compared with only 39% of the less severe group.
    • The clinics looked at the incidence of hospitalisation with CLL in all their CLL patients on various treatments: Ibrutinib: 27 out of 1729 (1.6%), venetoclax: 8/442 (1.8%), chemotherapy: 18/428 (4.2%). The difference between the following groups was statistically significant chemotherapy higher rates than ibrutinib or venetoclax. Ibrutnib hospitalisation rates were lower than all other treatments and even than those not on treatment.
    • This does provide some evidence to support the belief that ibrutinib treatment may cause the least immune compromise of all CLL treatments.
    • My own thought is that perhaps the high rate of severe COVID19 disease in untreated patients may perhaps reflect a reduced tendency for those groups to take strict social distancing measures, perhaps putting them at greater risk of exposure to a higher viral load.

UPDATE 8 July 2020

Case studies in the published literature are limited but I want to share two papers which together cover three patients with blood cancer. They are interesting as it seems to demonstrate the reason why many patients with blood cancer have a very difficult time fighting off this disease. Remember that many people with blood cancer will be able to fight off COVID-19, but some can’t and we just can’t at the moment predict who those will be.

The first article reported on two cases where following rituximab treatment (which suppresses lymphocytes) the patients caught COVID19 and had a long period of still producing positive antigen swab tests, and ultimately died. Neither of the patients were very elderly (65, 66), both had been treated with rituximab two weeks before catching COVID19. One of them was also on ibrutinib.

Both of the patients had the characteristic chest xrays which show the pneumonia associated with COVID-19. Clearly this shows it IS possible for immune compromised patients to develop this syndrome. Both patients are described as experiencing a massive cytokine storm. Thus whilst the immune system was presumably sluggish at the beginning of the disease and was not able to reduce the levels of virus which reached their blood, their sytems did however ultimately go into overdrive. This case report also contains a short review of the literature and cites evidnce that ibrutinib treatment is also associated with an increased risk of viral infections.(source: https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.16896 )

Whilst clearly immediately after rituximab therapy there are going to be very few lymphocytes present, that remains true for some time in many patients after successful treatment of their blood cancer even with other treatments. My lymphocyte counts remain under 1 (thousand) even 21 months after starting my chemotherapy treatment which contained Rituximab. I also have reduced antibody levels in my blood. But even before treatment many patients with blood cancer will have poorly functioning or few “healthy” lmphocytes.

It is possible that looking at blood antibody levels might be a way of indicating which patients are at the highest risk, but that might be deceptive. Much of our blood antibodies are produced by plasma cells which tend to be less effected both by cancer and the treatment of it. They are not able to produce antibodies to new infectious agents which the body hasn’t seen before, however, that is the role of the lymphocytes.

One reason then for the increased risk of many patients with blood cancer is therefore clearly the lack of properly functioning lymphocytes and therefore the absense of an antibody response. That immediately gives rise to the question: will giving antibodies from other people help? First principles suggests as much, and so convalescent plasma has been used. The third case I wish to share with you looked very much like they were following the same course as the other two but improved dramatically when given convalescent plasma (the antibodies from people who have recovered from COVID-19).

If you have a friend or family member who has had COVID-19 please encourage them to donate their plasma.

This third patient had ten positive nasal swabs for COVID-19, having also caught COVID-19 following rituximab infusion. She showed no sign of developing antibodies naturally. She was severly unwell with the characteristic x-ray changes. At day 50 of her admission she was given convalescent plasma and rapidly recovered.

Of coruse this is not a randomised contolled trial but offers an important glimmer of hope. It remains the case that blood cancer patients should make extrodinary efforts not to catch COVID-19. But if one of us does catch the disease, certainly one possilbe treatment, that might possibly be considered with a medical team, is convalescent plasma. Clearly there is no guarentee this will work for everyone and not every local hospital will be in a position to offer this experimental treatment.

“No adverse events occurred. The patient tested positive for Sars-Co-V2 anti-Nucleocapsid and anti-Spike IgG after the two first plasma units. Her health condition quickly improved, allowing to definitively withdraw
oxygen, apyrexia ensued, and a decrease in CRP level within 24 hours was objectified. SARS-CoV-2 RNA became undetectable on Day 57 and remained negative on Day 62. She returned home on Day 69 and completely recovered after 17 additional days of follow-up.

Source: https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.16981

Original Post

Blood Cancer UK recently published an important report which outlines the data supporting the theory that anyone with blood cancer is at more risk than the general population. This group of the UK population have been told to stay at home and not leave for any reason except to go to medical appointments.

I am aware that the approach of the UK government and health service on this point seems to be quite unique but this data is surely of interest for any blood cancer patient in the world as they think about their own risk assessment and plans to try and avoid catching coronavirus.

In this article I will highlight some of the key data points they explain and share a couple more, one of which is a huge UK based study that has been published online since the Blood Cancer UK article was released. Links to both articles are below.

It should be emphasised that all this data does seem to apply to people with any stage of any blood cancer. This seems to include watch and wait and remission.  Blood Cancer is a disease of the immune system so it makes logical sense that forming antibodies to infections we have not seen before is likely to be less efficient than in healthy people.

There are examples in both the scientific literature, various online news sources, and forums such as this of people with blood cancer even during the initial watch and wait phase who have got COVID19. Some have sadly died. One of these deaths was a sportsman in his twenties who had no idea they had an undiagnosed blood cancer. On the other hand some patients with blood cancer have got very unwell needing ventilator support but recovered. And others have had relatively minor disease and recovered. 

It is probably the case that, as a UK government scientist explained in one of the early press briefings, even if you are in an at risk group if you unfortunate enough to get COVID19 the majority of patients will recover.

But the data I will summarise below and which is explained more in the Blood Cancer UK article underlines that there is indeed a higher risk for us than the rest of the population. And because of that risk the UK government has advised all Brits who have ever had a Blood Cancer diagnosis too strictly shield at home having no contact with anyone that could give us the virus. 

I share this information not to cause anyone to be fearful. But to help us as we evaluate our own response to this disease, based if we are in the UK on the Government advice which is supported by the three major blood cancer charities (CLLSA, Leukaemia Care and Blood Cancer UK), the national NHS, and the CLL Forum who are the top CLL experts in the country. Local health professionals ought not to contradict this advice. 

Also for those who live in a different country that has not issued similar advice, this data is offered for you to consider as you do your own risk assessment. 

Although the UK appears to be the only country going to such lengths to try and keep their blood cancer patients safe, global CLL experts including in the USA agrees with the vital need to try and prevent patients with that blood cancer in particular from being exposed to COVID19. The CLL Society undertook a global survey of CLL experts which also examined how the experts are managing issues like should they stop chemo or IVIG at this time. The whole article makes fascinating reading but on the subject of this article the feedback of this group of blood cancer experts was clear and unambiguous:-

The CLL specialists uniformly recommended strict social isolationfor patients with CLL and emphasized the importance of primary pre-vention

https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.25851

I personally decided to temporally move out of my family home, leaving behind my wife and five children because it did not seem possible to safely shield in that house when my wife is a key worker and some of my children are volunteering at the food bank and helping to recored online church services. I am currently staying with my elderly parents and all three of us are strictly shielding and have not left the property for any purpose whatsoever for many weeks now. As a result we feel safe and are eating together, and living as a family unit as best we can within the confines of this place as I know many of you are doing as well. 

As you can imagine this has been hard, and represents a huge sacrifice, as does obeying the strong advice NOT to even go out for a walk. This will all feel harder as others in society begin to return to a more normal way of life. 

And due to severe hay fever symptoms I am staying indoors and not even going into the garden at the moment. But for me I am not full of fear because I know that I cannot get COVID19 right now. And I remind myself that it is well worth making a short term sacrifice (even if that extends to six months or more!) in order to maximise my chances of hopefully having decades of more life with my family. Personally I am not going to allow myself to be tempted to relax my isolation until it is clearly safe to do so. 

Some of what follows is a little technical though I have tried to make it as understandable as possible.  If you would rather not learn about statistics or may find them alarming I invite you to stop reading now.

Key points from Blood Cancer UK article

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* “If you’ve got blood cancer then you’re seven times more likely to end up needing intensive care as a result of coronavirus than an average person.” Note that this is despite the fact that we have been shielding, and so these figures probably largely reflect those who caught COVID19 before we started to stay home strictly and might well have been a lot higher if shielding had not been introduced.

*UPDATE: by May the proportion of patients in ITU with a blood cancer had gone up and not down. This is despite UK patients being urged to remain strictly isolated at home, only leaving their property to attend essential medical appointments. Blood Cancer UK now concludes

“Research has shown that, along with organ transplantation, blood cancer is the health condition that most increases people’s risk of becoming seriously ill with coronavirus.”

https://bloodcancer.org.uk/news/number-patients-coronavirus-intensive-care-blood-cancer-doubles/

In UK ONS data “Blood cancer was listed as one of the most common underlying health conditions in coronavirus-related deaths for males aged 0-44 and in women aged 55-59”

Source: Blood Cancer UK

Additional Data not included in the article

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ASH Prospective International Registry Source: ASH

* 27% of patients with Blood cancer and a COVID19 infection died.

*37.5% of patients with CLL and a COVID19 infection died

It should be noted that the numbers are small, and these estimates clearly represent reported case fatality rate rather than infections since no country is currently identifying many mild or asymptomatic cases. 

New UK GP Study of 17 Million People source: Medrxiv

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This study has looked at 17 MILLION people in the UK who are registered with a GP who uses a specific computer system. This is by far the largest study of its kind for COVID19 in the world. 

It looks at the risk of dying in hospital from COVID19. I.e. it is asking how many people with different characteristics ended up dying in hospital from COVID19 and what factors are associated with being more likely to have that sad outcome. This is not the same as the risk of dying if you catch the disease as it rather includes the risk of catching and dying from the disease in one measure. 

The Hazard ratio for blood cancer was estimated and after adjusting for age and other factors that might also influence mortality from COVID19 these came out as 3.52 ( possible range 2.41-5.14) for those diagnosed in the last year, 3.12 (2.50-3.89) for those diagnosed between 1 and 5 years ago and 1.88 (1.55-2.29) for those diagnosed more than 5 years ago. These were among the highest individual risk factors of any condition.

A Hazard Ratio can be thought of as essentially indicating how much more likely an event is to happen. Thus for those who have been diagnosed with blood cancer within the last year the estimated risk they died from COVID was 3.5 times the normal population, and for one to five years the risk was 3 times the normal population and for those diagnosed longer ago it was approximately 2 times the risk of the normal population.

So here we are seeing that across the groups estimates the range for the estimate of the additional risk for having blood cancer (adjusted for age and other factors) would be from 1.5 times the normal risk of dying from Covid to 5 times the normal risk. 

That is quite a broad range of uncertainty and reflects that even a study of 17 million is not large enough nor has their yet been long enough time to give an absolute answer to this question. Everyone agrees that sadly before this epidemic is over a lot more people will die and so these estimates will become more accurate over time. But it would certainly seem to be the case the real risk must be significantly over 1 as the HR ranges do not come close to overlapping 1 (i.e. the lower range is not less than 1). 

Mathematically you could in theory multiply those numbers by the risk for the general population of your own age and come up with an individual estimated risk. 

Perhaps surprisingly there is a hint of a suggestion that the longer you have had blood cancer the less likely you are to die from COVID19 in hospital in the UK. Now remember this is not talking about the risk if you catch it but rather the risk dying from COVID19 being in the group described. 

However we should note that these numbers will all be lower than they would otherwise be because of shielding. And since if you are shielding carefully it is essentially impossible to catch COVID19. So if we all carry on shielding when this study is repeated in a few months these numbers may all come down further because people who are not shielding are obviously more likely to catch COVID19 in the first place.

So actually, and this is a hypothesis we cant be sure of, but if the trend towards a lower risk for those who have had blood cancer for longer is real (hard to say for sure when you look at the ranges around the estimates) then maybe that is because those patients were more likely to be already at least partially self isolating even before the letters came out. Some of the people with blood cancer who have sadly died will have caught the disease before any lockdown or shielding instructions were issued. And so if people who have had blood cancer for longer are less likely to work, travel on public transport, and perhaps were quicker to respond to the advice from the government to shield then maybe that is why the estimate of the risk appears that their risk in practice was lower, but perhaps if nobody with blood cancer was shielding their risk might even have turned out to be higher than the newly diagnosed. We just don’t know.

Clearly we should be very careful to interpret too much into these findings. Except that it is another piece of evidence that strongly suggests that even though many of us have been shielding, there has up until now still been a significantly greater chance that people with blood cancer will die from COVID19 in the UK. But remember many of these people would have caught the disease before shielding or lock down started.

If every single patient with blood cancer decided in the light of this data to carefully shield themselves then none of us would get COVID19 (except perhaps a few of us if we had to be admitted to hospital for some other reason and unfortunately caught it there) So when this study is repeated later on we might see these numbers drop lower and even ironically we might even then appear to be at lower risk than other people who don’t have blood cancer particularly once they start to lift lock down.

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Conclusion

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I believe that the data shows that UK society as a whole are doing us a great favour by giving me and other Brits with blood cancer the advice and opportunity to shield and so avoid this risk.

If you are shielding carefully with your whole household you should not see any of this data as something to be anxious about since you are fully safe from COVID right now. If you live in another country you may decide you want to take similar actions to reduce your personal risk.

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Sources

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UK study examining risk of COVID19 death in GP patients https://www.medrxiv.org/content/10.1101/2020.05.06.20092999v1.full.pdf 

Blood Cancer UK: “Why are people with Blood Cancer being told to shield?”

https://bloodcancer.org.uk/news/why-are-people-blood-cancer-being-told-shield-12-weeks/

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Adrian Warnock
  • Adrian Warnock
  • Dr. Adrian Warnock is a medical doctor and clinical research expert who was himself diagnosed with blood cancer in May 2017. Adrian worked in the pharmaceutical industry for fifteen years helping to run the clinical trials that bring us new medicines and communicate the results. Before this he practised in the UK’s National Health Service (NHS), as a psychiatrist, for eight years.

    Adrian is a published author, the founder of Blood Cancer Uncensored, and has written a Christian blog since 2003 at Patheos. He is passionate about learning how to approach suffering with hope and compassion. Adrian's articles are not medical advice and he is not a haematologist or blood cancer doctor. Always seek individualised advice from your health care professionals. You can e-mail Adrian here.