tag:theconversation.com,2011:/us/topics/blood-cancers-36834/articlesBlood cancers – The Conversation2022-07-13T12:29:46Ztag:theconversation.com,2011:article/1844272022-07-13T12:29:46Z2022-07-13T12:29:46ZGut bacteria nurture the immune system – for cancer patients, a diverse microbiome can protect against dangerous treatment complications<figure><img src="https://images.theconversation.com/files/473639/original/file-20220712-26-brwdj.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1999%2C1499&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Stem cell transplants involve completely eliminating and then replacing the immune system of a patient, often by transplanting the bone marrow.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/red-bone-marrow-100x-light-micrograph-royalty-free-image/1168856200">xia yuan/Moment via Getty Images</a></span></figcaption></figure><p>One promising treatment for patients with blood cancers is <a href="https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/stem-cell-transplant/why-stem-cell-transplants-are-used.html">stem cell transplantation</a>. Doctors completely eliminate the patient’s immune system by aiming chemotherapy, radiation or both at their bone marrow before replacing it with a donor’s immune system. Because the bone marrow produces blood and immune cells, completely substituting cancerous bone marrow with healthy cells could help the body reestablish a functioning immune system and replace cancerous blood cells.</p>
<p>This procedure is not without risks. A key complication <a href="https://scholar.google.com.au/citations?user=jjjJeeEAAAAJ&hl=en">hematologists like me</a> worry about is <a href="https://my.clevelandclinic.org/health/diseases/10255-graft-vs-host-disease-an-overview-in-bone-marrow-transplant">graft-versus-host disease</a>, where the donor’s immune system recognizes the patient’s body as “foreign” and launches an attack. <a href="https://www.ncbi.nlm.nih.gov/books/NBK538235/">Up to 50% of patients</a> who receive a stem cell transplant develop graft-versus-host disease.</p>
<p>One unexpected part of the body that may play a key role in protecting transplant patients from complications, however, is their gut bacteria.</p>
<p>Alongside my colleagues <a href="https://www.mskcc.org/research/ski/labs/members/hana-andrlova">Hana Andrlova</a> and <a href="https://www.mskcc.org/research/ski/labs/marcel-van-den-brink">Marcel van den Brink</a>, <a href="https://research.fredhutch.org/markey/en.html">I</a> study how the composition of your microbiome, or the microorganisms living in your body, can affect how well cancer treatments work. While <a href="https://doi.org/10.1056/NEJMoa1900623">previous studies</a> have shown that disruptions to the diversity of organisms in the gut microbiome is linked to a higher risk of death after transplantation, the precise reasons for this are not clear.</p>
<p>In our <a href="https://doi.org/10.1126/scitranslmed.abj2829">recently published study</a>, we found that gut bacteria help the immune system recover from stem cell transplants by nurturing two special types of immune cells that protect against complications.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/oLMWPgo6jUY?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Allogeneic stem cell transplants involve taking the bone marrow of a donor and giving it to a patient through an IV.</span></figcaption>
</figure>
<h2>Gut bacteria and T cells</h2>
<p>To explore the relationship between gut bacteria and the immune system, we first needed to identify the types of bacteria present in a given microbiome. So we sequenced all the bacterial genes in the stool samples of 174 stem cell transplant patients. We then took blood samples from the same patients to identify which types of immune cells were circulating and how they were functioning.</p>
<p>We learned that a diverse intestinal microbiome after transplantation is associated with expansion of a particular type of cell called <a href="https://doi.org/10.1038/s41577-019-0191-y">MAIT, or mucosal-associated invariant T cells</a>. MAIT cells are linked to improved transplant outcomes like a lower risk of graft-versus-host disease and longer survival in both <a href="https://doi.org/10.1172/JCI91646">mice</a> and <a href="https://doi.org/10.1016%2Fj.bbmt.2017.10.003">people</a>. We found that the more MAIT cells patients had in their blood after transplant, the longer they survived and the fewer their complications. Patients with the highest levels of MAIT cells had the lowest incidence of graft-versus-host disease.</p>
<p>The precise mechanism behind the protective effects of MAIT cells is unclear. But researchers do know that these cells require molecules that come from the process of producing <a href="https://doi.org/10.1111/imcb.12057">riboflavin, or vitamin B2</a>, in the body to develop and multiply. Turns out, these riboflavin derivatives are produced by the microbes in the gut. </p>
<p>We also found that high MAIT cell numbers were linked to the presence of another special population of T cells, <a href="https://doi.org/10.1038/ni.3298">V-delta-2</a>, that are also stimulated by bacterial byproducts. Above-average levels of these cells were also associated with better survival and less graft-versus-host disease in transplant patients.</p>
<p>These findings suggest that one of the reasons why a healthy, diverse microbiome is <a href="https://doi.org/10.1056/NEJMoa1900623">linked to good results for stem cell transplant recipients</a> could be that gut bacteria support the development of immune cells that protect against transplant complications like graft-versus-host disease.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/473680/original/file-20220712-20-4xv5oq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Person lying in bed attached to tubes donating bone marrow" src="https://images.theconversation.com/files/473680/original/file-20220712-20-4xv5oq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/473680/original/file-20220712-20-4xv5oq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=327&fit=crop&dpr=1 600w, https://images.theconversation.com/files/473680/original/file-20220712-20-4xv5oq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=327&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/473680/original/file-20220712-20-4xv5oq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=327&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/473680/original/file-20220712-20-4xv5oq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=412&fit=crop&dpr=1 754w, https://images.theconversation.com/files/473680/original/file-20220712-20-4xv5oq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=412&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/473680/original/file-20220712-20-4xv5oq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=412&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Stem cells can also be donated through the blood circulating in the body instead of directly from the bone marrow.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/high-angle-view-of-person-during-bone-marrow-royalty-free-image/678898899">Dani Blanchette/EyeEm via Getty Images</a></span>
</figcaption>
</figure>
<h2>Protecting against transplant complications</h2>
<p>Our next step was to figure out how these special T cells protect against transplant complications. We took blood samples from five patients who had high numbers of MAIT and V-delta-2 cells. We then used a technique called <a href="https://doi.org/10.1186/s13073-017-0467-4">single-cell RNA sequencing</a> to analyze thousands of individual cells and explore all the potential functions any particular cell type may have in the body.</p>
<p>When we compared the MAIT and V-delta-2 cells of transplant patients and healthy people, our findings were very surprising. We had originally hypothesized that genes linked with tissue repair would be active in these T cells – that would explain why patients with high numbers of these cells do better after such intense treatment that’s so tough on the body. Instead, we found that these cells had highly expressed genes involved in inflammatory processes with the capacity to induce cell damage – sometimes necessary to fight off infections when the patient’s immune system is still recovering. This suggests that MAIT and V-delta-2 cells may be protecting patients from transplant complications in ways that we haven’t previously been aware of or understood.</p>
<p>It’s possible that T cells that are activated by the microbiome like MAIT and V-delta-2 help reduce transplant complications by killing infected cells or cells involved in graft-versus-host disease. While we aren’t able to confirm this hypothesis with our study, future work may help scientists better understand the important links between the microbiome, the immune system and successful stem cell transplants for cancer patients.</p><img src="https://counter.theconversation.com/content/184427/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kate Ann Markey holds equity in and is on the advisory board of PostBiotics Plus. She receives funding from the DKMS and the American Society of Hematology. </span></em></p>Patients with blood cancer undergoing stem cell transplantation have a high risk of complications. The bacteria in their gut, however, can help their immune system recover and fight infections.Kate Ann Markey, Assistant Professor of Medical Oncology, School of Medicine, University of WashingtonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1297212020-01-15T19:04:22Z2020-01-15T19:04:22ZCancer treatment: study finds targeting nearby ‘normal’ cells could improve survival rates<figure><img src="https://images.theconversation.com/files/310256/original/file-20200115-134777-1edjve6.jpg?ixlib=rb-1.1.0&rect=35%2C0%2C5955%2C3988&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A leukemia cell. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/hairy-cell-leukemia-3d-illustration-hematological-1152061151">Kateryna Kon/ Shutterstock</a></span></figcaption></figure><p>Cancer of the immune system, called <a href="https://www.cancer.gov/types/leukemia">lymphoma or leukaemia</a>, generally affects the entire body’s bone marrow and lymph nodes. Because these types of cancers are so widespread, surgery isn’t useful, so patients are usually treated with <a href="https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq">chemotherapy</a>. Although these treatments have <a href="https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/non-hodgkin-lymphoma/mortality?_ga=2.264442511.1217646422.1579043104-1856669782.1500315118#heading-Two">become significantly better</a> in the past ten years, lymphoma and chronic leukaemia often come back months or years after treatment. </p>
<p>Effective treatment options for these types of cancer become increasingly limited over time as tumours become resistant to chemotherapy after several rounds of treatment. For <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585532/pdf/medi-96-e7988.pdf">most patients</a>, a cure is out of reach, so the goal of treatment is instead to control the cancer for as long as possible. There’s a huge need to improve therapies that can eliminate cells that are resistant to chemotherapy and prevent the disease from reoccurring.</p>
<p>However, my colleagues and I recently identified a new achilles heel or blood cancers. <a href="https://stm.sciencemag.org/content/12/526/eaax9340">Our research</a> found that treating the normal cells near to the cancer cells with a type of drug known as <a href="https://www.ncbi.nlm.nih.gov/pubmed/27813176">small molecule inhibitors</a> significantly improved the effects of a broad range of chemotherapies. </p>
<p>In fact, in one test, this combination therapy extended the length of survival over 90% longer than using chemotherapy alone. This shows that cancer cells which would normally have resisted and survived chemotherapy, could now be eliminated from the body. Not only does this give patients a new kind of treatment, it also has the potential to cure patients who have to live with the disease for the rest of their lives.</p>
<h2>Re-purposing treatments</h2>
<p>Like with any living organism, cancer cells don’t like to live in isolation. They communicate with other cells as part of a larger system, known as the <a href="https://www.nature.com/collections/khylqkxqbr">microenvironment</a>. By communicating with nearby cells, cancer cells receive a <a href="https://jcs.biologists.org/content/125/23/5591">constant supply of nourishment</a> in the form of anchorage proteins, secreted growth factors, and metabolites produced by the cancer’s neighbouring, normal cells. These normal cells, known as “stroma”, are an <a href="https://www.nature.com/articles/nrc1477">essential component of most cancers</a> because they support tumour growth and survival. Without nourishment from stroma, cancer cells usually die.</p>
<p>Researchers have often wondered what effect isolating cancer cells from neighbouring stroma cells would have on cancer treatment. But the biggest challenge researchers faced was knowing what cells in the microenvironment to target and how to tailor treatments to these cells.</p>
<p>In a previous study, we found that lymphoma and leukaemia cells actually cause inflammation in stroma cells and that these cells also produce a protein, called <a href="https://www.cell.com/cancer-cell/fulltext/S1535-6108(12)00515-6"><em>kinase C (PKC)-beta</em></a>, after coming in contact with cancer cells. We’ve now found that this protein causes resistance to chemotherapy in cancer cells. </p>
<p>But we also found that when a stroma cell’s genes made it unable to produce this protein, it developed resistance to lymphoma and leukaemia. Knowing the role that this protein plays gives us a way of interfering in the communication that takes place between cancer and stroma cells – effectively cutting the lifeline for cancer cells, and ideally enhancing the effects of cancer therapies.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/310257/original/file-20200115-134772-l9l9ek.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/310257/original/file-20200115-134772-l9l9ek.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/310257/original/file-20200115-134772-l9l9ek.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/310257/original/file-20200115-134772-l9l9ek.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/310257/original/file-20200115-134772-l9l9ek.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/310257/original/file-20200115-134772-l9l9ek.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/310257/original/file-20200115-134772-l9l9ek.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Combining PKC-inhibitors with chemotherapy will make treatments more effective.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/cancer-patients-receiving-chemotherapy-treatment-hospital-529109200">napocska/ Shutterstock</a></span>
</figcaption>
</figure>
<p>Luckily, drugs that block the function of the PKC protein have already been developed. These weren’t considered to be a useful cancer treatment after clinical trial failures. Part of the reason for this failure is because these drugs were designed to kill cancer cells directly – which was <a href="https://ascopubs.org/doi/full/10.1200/jco.2015.65.7171">shown to be ineffective</a>. </p>
<p>But as our team showed, re-purposing these drugs to directly target stroma cells next to tumours – not the cancer cells – makes cancer cells more vulnerable to chemotherapy. Simultaneously, targeting cancer cells with chemotherapy and stroma cells with PKC-inhibitors is better than using either treatment alone. This “double strike” on immune cancers has the potential to significantly enhance current treatments and extend life expectancy for many patients.</p>
<p>In our study, the positive effects of PKC-inhibitors were seen in combination with many different types of chemotherapy – even newer medicines. Using this double strike approach was beneficial for not just one, but many different types of leukaemia and lymphomas, including <a href="https://www.nhs.uk/conditions/chronic-lymphocytic-leukaemia/">Chronic lymphocytic leukaemia</a>, <a href="https://www.nhs.uk/conditions/acute-lymphoblastic-leukaemia/">Acute lymphoblastic leukaemia</a>, and <a href="https://www.macmillan.org.uk/information-and-support/lymphoma/lymphoma-non-hodgkin/understanding-cancer/types-of-non-hodgkin-lymphoma/mantle-cell-lymphoma.html">Mantle cell lymphoma</a>. </p>
<p>This new treatment method might benefit hundreds of thousands of people currently diagnosed who are under observation or treatment. If these results can be replicated in further trials, it could become a new backbone for blood cancer therapy.</p><img src="https://counter.theconversation.com/content/129721/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ingo Ringshausen receives funding from AstraZeneca, not relevant to this research. His research is funded by Cancer Research UK (CRUK) </span></em></p>Our team found that chemotherapy can be made more successful by treating nearby ‘normal’ cells with protein-blocking drugs in lymphoma and leukemia.Ingo Ringshausen, Clinician Scientist and Consultant Haematologist, University of CambridgeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1279862019-11-29T00:52:11Z2019-11-29T00:52:11ZClive James raised awareness of leukaemia, part of his rich and valuable legacy<p>Clive James has left a valuable legacy of astute observation and witty interpretation of his world through his writing. He has also left another legacy. He has increased public awareness of leukaemia by sharing his cancer diagnosis over the decade before his recent death.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1199744664133361665"}"></div></p>
<p>Clive was <a href="https://www.dailymail.co.uk/tvshowbiz/article-1382299/Im-battling-leukaemia-reveals-broadcaster-Clive-James.html">diagnosed with</a> leukaemia in 2010 along with <a href="https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/kidney-failure">kidney failure</a> and the lung condition <a href="https://www.healthdirect.gov.au/emphysema">emphysema</a>. When he discussed his illness publicly in 2012, <a href="https://www.bbc.com/news/entertainment-arts-18532310">he said</a>:</p>
<blockquote>
<p>I’m getting near the end. I’m a man who is approaching his terminus.</p>
</blockquote>
<p>So, many people may be surprised to hear he died nine years after this diagnosis.</p>
<h2>What is leukaemia?</h2>
<p><a href="https://www.cancervic.org.au/cancer-information/types-of-cancer/leukaemia/leukaemia-overview.html">Leukaemia</a> is a cancer in the bone marrow where the white blood cells are formed. This results in the production of greatly increased numbers of abnormal white cells in the blood. These crowd out the production of normal blood cells. </p>
<p>The condition is called acute leukaemia if it develops rapidly, or chronic leukaemia if it progresses slowly.</p>
<p>The type of leukaemia is defined by what type of white cells are affected. For example, lymphocytes are a type of white blood cell that help the body fight infection by producing antibodies. If they become cancerous, lymphocytic leukaemia results.</p>
<p>Leukaemia develops when the genes which help control the growth of the lymphocytes become altered. What causes this damage is not clear but there can be an increased risk in some families. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-can-go-wrong-in-the-blood-a-brief-overview-of-bleeding-clotting-and-cancer-76400">What can go wrong in the blood? A brief overview of bleeding, clotting and cancer</a>
</strong>
</em>
</p>
<hr>
<p>Clive James had <a href="https://www.leukaemia.org.au/disease-information/leukaemias/chronic-lymphocytic-leukaemia/">chronic lymphocytic leukaemia</a>. Around 1,000 Australians each year are diagnosed with this type. It’s most common in people over 60, and more common in men than women.</p>
<p>People can go to their doctor looking pale, and complaining of tiredness and breathlessness when exercising. They are anaemic (have low levels of red blood cells), and have high levels of white blood cells.</p>
<p>They may bruise easily and are prone to infections. Glands in the neck, the armpits and the groin may be swollen or there may be discomfort under the left rib cage because of a swollen <a href="https://www.health.qld.gov.au/news-events/news/facts-about-your-spleen-splenectomy-immune-system-what-is">spleen</a>. They may have lost weight and have started to sweat at night.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/304355/original/file-20191128-178121-1b09t4x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/304355/original/file-20191128-178121-1b09t4x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/304355/original/file-20191128-178121-1b09t4x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/304355/original/file-20191128-178121-1b09t4x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/304355/original/file-20191128-178121-1b09t4x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/304355/original/file-20191128-178121-1b09t4x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/304355/original/file-20191128-178121-1b09t4x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/304355/original/file-20191128-178121-1b09t4x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=504&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Some people do not have any symptoms. They find out they have chronic lymphocytic leukaemia after having a blood test for some other reason.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/medical-equipment-blood-test-327930539">from www.shutterstock.com</a></span>
</figcaption>
</figure>
<p>Many of these symptoms could be due to other causes such as a viral infection. But a diagnosis of leukaemia is made with a blood test showing increased numbers of white blood cells or a <a href="https://www.petermac.org/services/diagnosis-investigations/bone-marrow-biopsy">bone marrow biopsy</a> (a sample taken of the bone marrow), which reveals the overgrowth of the abnormal white blood cells. </p>
<p>Some people do not have any symptoms. They find out they have chronic lymphocytic leukaemia after having a blood test for some other reason.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/vale-clive-james-a-marvellous-low-voice-whose-gracious-good-humour-let-others-shine-127992">Vale Clive James – a marvellous low voice whose gracious good humour let others shine</a>
</strong>
</em>
</p>
<hr>
<h2>How is it treated?</h2>
<p>People with chronic lymphocytic leukaemia don’t need to be treated until they have symptoms. So it may be several years before treatment starts.</p>
<p>Then, the treatment is chemotherapy, commonly with the drugs <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697528/">fludarabine</a> and <a href="https://medlineplus.gov/druginfo/meds/a682080.html">cyclophosphamide</a>. These are often combined with an antibody, <a href="https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancer-drugs/drugs/rituximab">rituximab</a>, which targets the abnormal white cells.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-what-is-chemotherapy-and-how-does-it-work-76403">Explainer: what is chemotherapy and how does it work?</a>
</strong>
</em>
</p>
<hr>
<p>These treatments will not cure the disease, but can help control it for long periods of time. Further drugs are also being developed. </p>
<p>People with chronic lymphocytic leukaemia are also advised to avoid infections, which may overwhelm a vulnerable or weakened immune system. Avoiding contact with people who are unwell, maintaining good personal hygiene and having flu shots <a href="https://www.cancercouncil.com.au/chronic-lymphocytic-leukaemia/treatment/chemotherapy/#Taking-care-with-infections">are among what’s recommended</a>.</p>
<h2>What’s the life expectancy?</h2>
<p>The life expectancy of a person diagnosed with chronic lymphocytic leukaemia can range from a few months to several decades. The mid-range is around ten years, as it was with Clive James. </p>
<p>Just over <a href="https://www.cancer.net/cancer-types/leukemia-chronic-lymphocytic-cll/statistics">80 out of 100 adults</a> diagnosed with chronic lymphocytic leukaemia will still be alive after five years. </p>
<p>This shows the type of leukaemia is vital to determining the time-course of the disease. Adults with chronic leukaemias survive much longer than those with acute leukaemias, where <a href="https://ashpublications.org/blood/article/126/23/5265/94661/Disease-Progression-and-Complications-Are-the-Main">only a quarter</a> of those diagnosed are expected to be alive five years after diagnosis.</p>
<p><a href="https://ashpublications.org/blood/article/126/23/5265/94661/Disease-Progression-and-Complications-Are-the-Main">About</a> just under half of people with chronic lymphocytic leukaemia die when the disease progresses. Others die of infections because their immune system is not working as well as normal, and one-fifth of people die of other cancers. One-quarter die of illnesses unrelated to their leukaemia.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-australians-die-cause-2-cancers-58063">How Australians Die: cause #2 – cancers</a>
</strong>
</em>
</p>
<hr>
<h2>The burden of multiple illnesses</h2>
<p>People can become very unwell when multiple illnesses add to their symptoms, reducing their quality of life. </p>
<p>An example is emphysema, permanent damage to the lungs often associated with heavy smoking. This restricted Clive James from flying and therefore returning to visit his Australian birthplace in his last years.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-what-is-chronic-obstructive-pulmonary-disease-25539">Explainer: what is chronic obstructive pulmonary disease?</a>
</strong>
</em>
</p>
<hr>
<p>Although unrelated to chronic lymphocytic leukaemia, emphysema could increase the likelihood of lung infections when paired with it. Other illnesses can also make a person too weak to tolerate the side effects of their leukaemia drugs.</p>
<p>Clive James entertained and informed us as he shared his observations on his life
through decades of writing. So it is fitting he should be publicly sharing the health issues that resulted in his death. As such, he provided one last opportunity to educate his readers — in this instance about leukaemia.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/clive-james-on-death-dragons-and-writing-in-the-home-stretch-27418">Clive James on death, dragons and writing in the home stretch</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/127986/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ian Olver does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Writer, broadcaster and commentator Clive James never missed an opportunity to educate his audience. That included raising awareness of leukaemia.Ian Olver, Professorial Research Fellow. School of Psychology, Faculty of Health and Medical Sciences, University of AdelaideLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/874972018-01-17T03:10:12Z2018-01-17T03:10:12ZHow rejuvenation of stem cells could lead to healthier aging<figure><img src="https://images.theconversation.com/files/198797/original/file-20171212-9389-cjsjns.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/group-senior-retirement-exercising-togetherness-concept-477077380?src=ZDmjg_uzXTaytUXq7fqnWg-1-5">Rawpixel.com/Shutterstock.com</a></span></figcaption></figure><p>“Rampant” and “elderly” are words rarely used in the same sentence, unless we are talking of the percentage of people over 65 years old worldwide. <a href="https://ourworldindata.org/life-expectancy/">Life expectancy</a> has considerably increased, but it is still unknown how many of those years are going to be lived in good health. </p>
<p>As a researcher of blood cancers and aging, I inevitably think about how in the next few decades a very large part of the population will deal with cancer treatments. Are we doing the best to manage the side effects, or even to manage aging itself? Could we accumulate just wisdom, instead of aches and pain?</p>
<p><a href="https://www.newscientist.com/article/mg22429894-000-everyday-drugs-could-give-extra-years-of-life/">Rejuvenation strategies</a> once sounded like science fiction, but they are becoming more and more promising. New research from my institute, Weill Cornell Medical College, suggests that transplantation of young blood vessel cells rejuvenates aged stem cells in mice, boosting older blood system function. It also shows signs that it could aid in recovery of the side effects of cancer therapy for humans. </p>
<h2>What happens to our blood system as we age?</h2>
<p>Of the over 7 billion people on Earth, more than <a href="http://www.who.int/world-health-day/2012/toolkit/background/en/">600 million are age 65</a> and older. This group, for the first time in human history, is expected by 2020 to be larger than the number of children below age 5. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544764/">Aging is a risk factor</a> for many conditions, such as blood cancer, so we can foresee that aging countries should prepare to deal with the consequences in health care. </p>
<p>The blood system, also called <a href="https://theconversation.com/essays-on-blood-why-do-we-actually-have-it-75064">the hematopoietic system</a>, is responsible for producing blood cells throughout a person’s life. We know that, with age, its function declines. </p>
<p>All blood cells derive from a hierarchical system, with common ancestor cells, called hematopoietic stem cells, at its apex. Over the course of a person’s life, these cells will continuously supply all types of blood cells that we need, including different types of immune cells. </p>
<p>As we age, blood stem cells become less able to perform at the best of their capability. This results in a decreased ability to fight infections and <a href="http://news.cornell.edu/stories/2017/10/transplantation-young-blood-vessel-cells-boosts-aging-stem-cells">increased incidence of blood cancer</a> in the over-65 population. </p>
<p>Older patients are also frequently not good candidates for bone marrow transplant, the cure for many blood disorders. This is because of a higher degree of complications after transplant, which is also limited by having enough numbers of stem cells to reconstitute the hematopoietic system in an adult. Therefore, strategies to support blood stem cell recovery are needed to expand the pool of possible bone marrow transplant recipients.</p>
<h2>Blood vessel cells and how they work</h2>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/198793/original/file-20171212-9396-y18q87.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/198793/original/file-20171212-9396-y18q87.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=481&fit=crop&dpr=1 600w, https://images.theconversation.com/files/198793/original/file-20171212-9396-y18q87.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=481&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/198793/original/file-20171212-9396-y18q87.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=481&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/198793/original/file-20171212-9396-y18q87.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=605&fit=crop&dpr=1 754w, https://images.theconversation.com/files/198793/original/file-20171212-9396-y18q87.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=605&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/198793/original/file-20171212-9396-y18q87.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=605&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Aged blood vessel cells, shown in red and green, with blue nuclei, with an age-associated defect.</span>
<span class="attribution"><span class="source">Michael Gutkin</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>Blood vessel cells, or <a href="https://www.ncbi.nlm.nih.gov/books/NBK26848/">endothelial cells</a>, are a particular cell type that lines the inside of blood vessels. They contribute to form arteries, veins and capillaries. For a long time, endothelial cells have been perceived as a passive conduit for blood. </p>
<p>However, in recent years, scientists have seen a new role for these cells. They discovered that blood vessel cells actively sustain nearby stem cells and guide organ regeneration. </p>
<p>So, instead of a pipe system, we can think of blood vessel cells more like active supporters lined up along a cyclist’s race. This dynamic role has been found to be true for many organs, including the one responsible for making new blood cells, the bone marrow. </p>
<p>In the marrow, blood stem cells are found in close contact with blood vessels cells, which provide many types of substances, such as <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=632169">KIT ligand</a> that stem cells need to keep performing at their best. </p>
<p>As we get older, endothelial cell supportive function declines, and they become dysfunctional. They can still perform the basic function of architectural support for blood flow, but they are less able to support nearby stem cells. </p>
<p>A <a href="https://www.jci.org/articles/view/93940">recent study</a> from Weill Cornell Medical College shows that older blood vessel cells made young blood stem cells act old. Led by Dr. Jason Butler and Dr. Michael Poulos, the research isolated blood vessel cells from young or old mice and grew them in petri dishes with blood stem cells. </p>
<p>The young blood stem cells bias showed a tendency toward producing more of one type of immune cells, myeloid cells, which is a hallmark of aging. </p>
<p>In a complementary experiment in the study, the youngster cells rejuvenated the old ones. The team found out that the rejuvenated old cells were able to create a healthy blood system when transplanted back into mice.</p>
<p>The group then gave mice a strong dose of whole body radiation, similar to what patients undergo prior to <a href="https://bethematch.org/patients-and-families/about-transplant/what-is-a-bone-marrow-transplant-/">bone marrow transplant</a>. Then, they infused the mice with endothelial cells isolated from young mice. They found that the blood vessel infusions enhanced the recovery of the hematopoietic system and restored blood stem cell function in aged mice.</p>
<p>When the team modeled a bone marrow transplant on the mice, they even observed that mice infused with endothelial cells regained a healthy blood system, even if the number of blood stem cell transplanted was suboptimal.</p>
<h2>Benefits ahead?</h2>
<p>The study shows that young blood vessels can potentially rejuvenate blood stem cell functions, and mitigate the effects of medically induced stress, such as <a href="https://www.mayoclinic.org/tests-procedures/radiation-therapy/details/risks/cmc-20325837">radiation therapy</a>. The endothelial cells also protected other organs affected by radiation throughout the body, including the gut, skin, spleen and liver. </p>
<p>This global protection has many <a href="https://news.weill.cornell.edu/news/2017/10/transplantation-of-young-blood-vessel-cells-boosts-function-of-aging-stem-cells">potential benefits</a> for those undergoing cancer therapy, Butler explained in a statement. Those benefits include a shorter recovery time, less susceptibility to infections and lower the number of blood stem cells needed to achieve a successful transplant. The infusion of endothelial cells could thus lower the complication rates for elderly patients, Butler said.</p>
<p>At this time several groups are exploring endothelial cells as support strategy for blood stem cells, in <a href="http://www.bloodjournal.org/content/109/6/2365.long?sso-checked=true">mice</a> and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442761/">nonhuman primates</a>. </p>
<p>Researchers agree on two very relevant issues that will influence the clinical application of these findings. </p>
<p>First, the infused blood vessel cells stick around transiently, which means lower chances of any potential toxic or unwanted side effect. Second, the infusions would work as an adjunct therapy for clinical protocols already in place, a sort of upgrade on standard treatment. This could potentially speed up the clinical translation of these findings.</p>
<p>“The bullets are already there; this is a better one,” said Poulos.</p><img src="https://counter.theconversation.com/content/87497/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Elisa Lazzari works for Weill Cornell Medical College.</span></em></p>As people’s bodies age, so do their blood cells. This affects immunity and an ability to withstand certain cancer treatments. A recent study in mice suggests that those cells can be rejuvenated.Elisa Lazzari, Postdoctoral Associate in Biomedical Sciences, Cornell UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/746352017-05-18T14:11:10Z2017-05-18T14:11:10ZKenyan study shines new light on chronic myeloid leukaemia<figure><img src="https://images.theconversation.com/files/167849/original/file-20170504-21608-131drfk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Chronic Myeloid Leukaemia develops silently often with no symptoms, particularly in the early stages.</span> <span class="attribution"><span class="source">shutterstock</span></span></figcaption></figure><p><em><a href="https://www.cancer.org/cancer/chronic-myeloid-leukemia/about/what-is-cml.html">Chronic myeloid leukaemia</a> is a type of bone marrow cancer that goes on to affect the blood, then other organs and tissues. Previous research has linked it to <a href="http://www.leukaemia.org.au/blood-cancers/leukaemias/chronic-myeloid-leukaemia-cml">exposure to high doses of radiation</a>. The Conversation Africa’s Health Editor Joy Wanja Muraya asked a team of Kenyan experts to explain their research into what other factors might predispose people to this type of cancer.</em></p>
<p><strong>What is chronic myeloid leukaemia and what encouraged your study?</strong></p>
<p>In sufferers of <a href="http://www.cancersupportcommunity.org/learn-about-cancer-types/myeloproliferative-neoplasms">chronic myeloid leukaemia</a>, the bone marrow produces <a href="http://www.leukaemia.org.au/blood-cancers/leukaemias/chronic-myeloid-leukaemia-cml">too many</a> white cells that gradually crowd the bone marrow, interfering with the normal production of blood cells. </p>
<p>One of the confirmed <a href="https://www.cancer.org/cancer/chronic-myeloid-leukemia/causes-risks-prevention/risk-factors.html">causes</a> of this cancer is exposure to an atomic weapon or nuclear accident radiation. Other risks are not well established.</p>
<p>In a <a href="http://ecommons.aku.edu/eastafrica_fhs_mc_pathol/125/">previous</a> study, we found that there were no clear environmental factors associated with it. But we set off to investigate the association between patients’ occupations and whether personal and family history of cancer increased the chances of getting chronic myeloid leukaemia.</p>
<p>The study found that there was no clear link between occupation and contracting the cancer. There was familial correlation with common cancers in the population, suggesting epidemiologic - occurrence of disease within a population - rather than a genetic link. </p>
<p>These findings are important because they add to the general body of knowledge about chronic myeloid leukaemia and opens the door to new avenues of research to identify what risks might be behind it.</p>
<p><strong>What was your study about?</strong></p>
<p>We studied 398 patients aged between 18 and 80 years diagnosed with chronic myeloid leukaemia. They were receiving treatment between November 2005 and April 2015 under a <a href="https://www.ncbi.nlm.nih.gov/pubmed/21591520">programme at Nairobi Hospital</a> that offers free <a href="http://www.newsmax.com/TheWire/gleevec-cancer-pill-chronic-myeloid-leukemia/2017/03/10/id/777968/">anti-cancer drugs</a>. The clinic treats patients from Kenya and other East African countries including Uganda, Tanzania, South Sudan, Burundi and Rwanda.</p>
<p>The <a href="http://www.davidpublisher.org/Public/uploads/Contribute/58b7bcd6793f1.pdf">study</a> investigated the kinds of jobs these patients were involved in. We also interrogated whether a family history of other cancers had placed them at a higher risk of getting chronic myeloid leukaemia.</p>
<p>Of the 398 patients studied, only 297 had a family history of cancer recorded. Others didn’t know if there were such cases in their families.</p>
<p>Three patients had something peculiar: all worked at the same premises, one had chronic myeloid leukaemia and two acute myeloid leukaemia. The cases were:</p>
<ul>
<li><p>a 33 year old information communication and technology male who was diagnosed with chronic myeloid leukaemia. He worked for a mobile phone company in Nairobi.</p></li>
<li><p>A 40 year old female who was diagnosed with acute myeloid leukaemia. She worked for the same telecommunications company and on the same floor. She was diagnosed in 2006.</p></li>
<li><p>A female worker in same company and office who was diagnosed with acute myeloid leukaemia in 2011.</p></li>
</ul>
<p>We concluded that these three employees in the same telecommunications office who developed myeloid leukaemias within a span of less than 10 years cannot be ignored. There is need for more intensive research in this area.</p>
<p><strong>What makes this study unique and important in understanding blood cancers?</strong></p>
<p>Generally, the best known <a href="https://www.cancer.org/cancer/cancer-causes.html">cancer causing agents</a> for all types of cancers include exposure to ionising radiation, chemicals and drugs, tobacco and alcohol consumption, infections, environmental pollutants and genetic factors.</p>
<p>For chronic myeloid leukaemia, the only confirmed link is with nuclear bomb radiation. Other associations such as exposure to benzene are largely <a href="https://www.ncbi.nlm.nih.gov/pubmed/20939751">weak</a>. For example, other studies have failed to show a <a href="http://ecommons.aku.edu/cgi/viewcontent.cgi?article=1139&context=eastafrica_fhs_mc_pathol">clear association</a> between farming and the development of this cancer.</p>
<p>But a case control study in <a href="https://www.ncbi.nlm.nih.gov/pubmed/2208120">Iowa and Minnesota</a> found pesticide exposure and other agricultural factors to be significant risk factors.</p>
<p>In our study, the numbers were too small to support a case that occupational exposure contributed to a person getting chronic myeloid leukaemia. Farming (the patients were mostly peasant farmers) topped the list of occupations at 19.7%, followed by those who worked in manual, outdoor jobs such as carpenters, builders, masons, painters and drivers, at 15.7%.</p>
<p>Evidence on linking cancer to electricity is mixed. On the one hand childhood leukaemia has been associated with exposure to <a href="https://www.ncbi.nlm.nih.gov/pubmed/18927133">residential electromagnetic fields</a>. But other studies have failed to show any connection between <a href="http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(99)10074-6.pdf">high voltage</a> power lines or mobile phones with leukaemia.</p>
<p>On a genetic link between chronic myeloid leukaemia, our study findings confirm earlier research that having a type of cancer in the family doesn’t increase a person’s chance to get this blood cancer. For example previous studies have shown that <a href="http://cancer.unm.edu/cancer/cancer-info/types-of-cancer/leukemia/chronic-myeloid-leukemia/chronic-myeloid-leukemia-screeningprevention/">identical twins</a> of patients with chronic myeloid leukaemia are not at greater risk than other siblings.</p>
<p>Cancers that were found among family members could be interpreted as having happened purely by chance since the cancers in question are the most common cancer types in our population.</p>
<p>Finally, there are two things we need to keep in mind from this study;</p>
<ul>
<li><p>more research among workers in the telecommunications industry should be carried out.</p></li>
<li><p>whereas one can ignore the familial link between chronic myeloid leukaemia and other cancers seen in this study because of small numbers, we should track down defective common downstream pathways that cells use for survival signalling. </p></li>
</ul>
<p>These could lead to cancer either by understanding the direct gene changes. It is also a chance to study epigenetics, the study of biological mechanisms that switch genes on and off.</p><img src="https://counter.theconversation.com/content/74635/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andrew Odhiambo is affiliated with Nairobi Radiotherapy & Cancer Centre, Nairobi West Hospital Cancer Unit and Eddah's Hope Cancer Foundation. </span></em></p><p class="fine-print"><em><span>Sitna Mwanzi has received a research grant from AstraZeneca </span></em></p><p class="fine-print"><em><span>Esther Dindi, Nicholas A. Abinya, and Peter Oyiro do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>One of the confirmed causes of Chronic myeloid leukaemia is contact with an atomic weapon or nuclear radiation. Other risks factors of this type of cancer are still being established.Nicholas A. Abinya, Professor of Medicine, section of Haematology and Oncology, University of NairobiAndrew Odhiambo, Assistant Lecturer in Internal Medicine & Medical Oncology/Haematology, University of NairobiEsther Dindi, Researcher, University of NairobiPeter Oyiro, Fellow Haematology-Oncology, University of NairobiSitna Mwanzi, Program Director, Department of Medicine, Aga Khan University Licensed as Creative Commons – attribution, no derivatives.