Spotlight on... blood cancers
Our latest 'spotlight on' article explores the risks, symptoms and available treatments for patients with blood cancers, such as leukaemia, lymphoma and myeloma.
What are blood cancers?
Blood cancers, a diverse group of diseases that includes leukaemia, lymphoma and myeloma, occur when the normal processes of blood cell production break down. Collectively, blood cancers are the fifth most common type of cancer, with over 30,000 people diagnosed each year in the UK.
Leukaemia – uncontrolled growth of immature white blood cells – can either be acute, meaning it is fast growing, or chronic, which develops more slowly. They can also be classified by the type of blood cell affected – lymphoid or myeloid – which give rise to the many types of infection-fighting immune cells. This means there are four main types of leukaemia:
• Acute lymphoblastic leukaemia (ALL)
• Acute myeloid leukaemia (AML)
• Chronic myeloid leukaemia (CML)
• Chronic lymphocytic leukaemia (CLL)
Lymphomas also affect the lymphoid cells, but appear as solid tumours in glands in the neck, chest, armpit or groin. Hodgkin lymphoma was the first type to be described, and all types after that were termed non-Hodgkin lymphoma. But we now know that there are 35 or so different sub-types of non-Hodgkin lymphoma, each one of which can have a different prognosis and will require different treatment.
Myeloma is a cancer of the plasma cells, a type of immune cell that normally produces antibodies. Abnormal plasma cells crowd out other cells in the bone marrow, affecting normal blood cell production. If left untreated, it can lead to painful bone damage, as well as anaemia and kidney problems.
"Collectively, blood cancers are the fifth most common type of cancer..."
Who is at risk?
Blood cancer can affect anyone, from infants to the elderly. They account for around one in 10 of all newly diagnosed cancers in the UK, and about one person in 25 will be diagnosed with a blood cancer in their lifetime.
While leukaemia is the most common form of cancer in children, affecting over 400 under 15s a year in the UK, it occurs in much greater numbers in adults, especially the elderly. The same is true for non-Hodgkin lymphomas, myeloma and the rarer blood cancers. In the UK, over 60 percent of cases of these cancers are in the over 65s, and the most common age group to be diagnosed with a blood cancer is the 70s. On the other hand, for Hodgkin lymphoma, which affects over 1,700 people in the UK each year, half occur in the 15-40 year old group.
Gender is also a factor. At most ages, men are more likely than women to be diagnosed with a blood cancer1.
Unlike the strong links between the 'BRCA' gene variants and breast cancer, or smoking and lung cancer, there are few clear cut genetic or lifestyle factors that mean some people are at significantly higher risk of developing leukaemia, lymphoma or myeloma.
Nevertheless, there is a growing body of evidence suggesting some influence of our genetic makeup. Research shows that susceptibility to CLL can be inherited as a result of the accumulating many different genetic variations, each of which ever-so slightly increase risk2. Similar work has highlighted genetic regions that influence the ageing process are also linked to myeloma and a variant that affects childhood ALL sub-type and associated clinical outcome3,4.
Scientists have also pinpointed the genetic error crucial to leukaemia forming in identical twins5. And some genetic conditions, such as Down syndrome and Fanconi anaemia, can raise the likelihood of AML.
Environmental factors are thought to play a relatively minor role. But other risk factors that have been identified include certain viral infections, previous radiation or chemotherapy and environmental pollutants.
What are the symptoms to look out for?
Symptoms vary depending on the type of blood cancer. They tend to be fairly general and can be confused for other common conditions, often making it difficult to spot6. It is, however, useful to know these signs to spot clusters of tell-tale symptoms. If a blood cancer is suspected, patients will generally be sent to a specialist for blood tests to confirm the diagnosis.
Acute leukaemia
Common symptoms for AML and ALL include:
• Unusual bleeding and bruising
• Pale skin
• Fatigue and breathlessness
• Frequent and persistent infections
Chronic leukaemia
Many patients are diagnosed with CML or CLL by chance through a routine blood test when the disease is still developing slowly, having had no symptoms at all.
"Nevertheless, there is a growing body of evidence suggesting some influence of our genetic makeup."
When CML symptoms are present they can include fatigue, loss of appetite, weight loss, sweating and unusual bleeding. If the spleen is enlarged, there may be abdominal discomfort.
Before their diagnosis, patients with CLL may have noticed signs such as tiredness, a swollen lymph node or frequent infections.
Lymphoma
The most common sign of Hodgkin and non-Hodgkin lymphomas is swelling of glands, or lymph nodes, in the neck, chest, groin or armpit. This swelling causes lumps that are normally painless and last for up to six weeks. Lots of common infections cause swollen glands but these are usually tender and shrink away quickly.
Other symptoms for both lymphomas include:
• Abdominal pain due to enlarged liver or spleen
• Night sweats
• Weight loss
• Itching
• Breathlessness
• Unusual bruising
• Recurrent infections
• Bone pain
• Fatigue
Myeloma
The most common symptom of myeloma is severe back pain, but other symptoms can include:
• Nausea
• Loss of appetite
• Constipation
• Fatigue
• Breathlessness
What treatments are available?
Treatment varies for each type of blood cancer but, with a few notable exceptions, generally still involves the use of one or a combination of:
• Chemotherapy drugs that work against highly active cells
• Radiotherapy to kill sensitive cancer cells
• A stem cell transplant to replenish normal bone marrow cells
In addition, a new wave of biological therapies that target specific processes in cancer cells have been developed.
Monoclonal antibodies
Drugs derived from our immune system called 'monoclonal antibodies' have been successful for over a decade in the treatment of CLL and many types of non-Hodgkin lymphoma. They work by seeking out and attaching themselves to a specific protein found only on the surface of cancer cells. The cancer cells are then 'flagged' to be destroyed by the immune system.
One of these drugs, Rituximab (trade name Mabthera), has become standard treatment, in combination with chemotherapy, for types of non-Hodgkin lymphoma. Unfortunately, a significant percentage of patients are unresponsive to Rituximab or go on to develop resistance to the drug.
Targeted drugs
The survival chances for CML patients have been transformed by the introduction of drugs called tyrosine-kinase inhibitors (TKIs). These drugs target specific molecular faults that drive the disease, meaning they're more effective at killing cancer cells and more likely to leave healthy cells alone. The first of these, imatinib (trade name Glivec), appeared just over a decade ago and has led to five year survival leaping from 30 percent to nearly 90 percent. Many patients can now live a normal life and keep their cancer under control simply by taking a single pill each day.
"The survival chances for CML patients have been transformed by the introduction of drugs called tyrosine-kinase inhibitors..."
We're now even running a clinical trial to test whether some patients can safely come off the drug altogether. Second generation TKIs, such as nilotinib (trade name Tasigna), are used if patients stop responding to imatinib or if they cannot tolerate side effects of the drug.
What is the outlook?
Fifty years ago, the prospects for a child diagnosed with leukaemia were dire – only one in 10 survived for five years or more, but thanks to research this has risen to between eight and nine in 107.
For adults, the survival rate is as high as 70–80 percent for some forms of blood cancer. Despite improvement in survival, however, over 12,000 people still die of blood cancers each year in the UK.
What is the future?
Research to improve treatment for blood cancers, as with cancers more generally, is moving away from traditional chemotherapy and towards drugs specifically designed to target the molecular faults driving a person's cancer – as exemplified by TKIs.
We understand more and more about the biological differences between individual cancers, so that we will be able to tailor treatments for individual patients according to their specific disease sub-type. By being more precise, this type of drug is more effective and results in fewer side effects. This means we can give the right treatment to the right person at the right time.
There is still the challenge of drug resistance and relapse, but work on the genetic variation within an individual cancer and how cancers evolve will help develop treatment strategies to overcome these. This often involves combining therapies to run cancer cells into a dead end.
"We understand more and more about the biological differences between individual cancers, so that we will be able to tailor treatments..."
Blood cancers tend to be some of the most common cancers diagnosed through emergency routes. These patients fare worse than those diagnosed earlier, so we need to address this through better symptom awareness and smarter diagnostic tests.
Scientists are developing newer tests based on sensitive cutting-edge DNA technology. These are not only more accurate in detecting the presence of a blood cancer but can efficiently segregate patients by disease sub-type, supporting the personalised approach to treatment. This type of test can also monitor a patient's response to treatment and their risk of relapse.
Finally, we want to stop people getting cancers in the first place. This means understanding more about the biology of pre-cancerous conditions, how they progress to full-blown cancer and how we can intervene to stop them.
References
1. The Haematological Malignancy Research Network: http://www.hmrn.org/Statistics/Incidence.aspx
2. 'A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia' published in Nature Genetics. Corresponding author: Dr Richard Houlston, Institute of Cancer Research, Sutton, Surrey. http://www.nature.com/ng/journal/v40/n10/abs/ng.219.html
3. 'Major study links ageing gene to myeloma' http://leukaemialymphomaresearch.org.uk/news-item/major-study-links-ageing-gene-myeloma
4. 'Childhood leukaemia can be inherited' http://leukaemialymphomaresearch.org.uk/news-item/first-concrete-evidence-susceptibility-and-survivorship-childhood-leukaemia-can-be
5. 'Identical twins' genes reveal the 'silent beginnings' of leukaemia.' http://www.icr.ac.uk/press/press_archive/press_releases_2013/23676.shtml
6. Information on symptoms of all types of blood cancer is available on the Leukaemia & Lymphoma Research website patient information section http://leukaemialymphomaresearch.org.uk/patient-information
7. CancerStats: Cancer Statistics for the UK. http://www.cancerresearchuk.org/cancer-info/cancerstats/
About the author:
Dr Matt Kaiser is Head of Research at Leukaemia & Lymphoma Research, the only UK charity dedicated to improving the lives of patients with all types of blood cancer, including leukaemia, lymphoma and myeloma. Its life-saving research is focused on finding causes, improving diagnosis and treatments, and running ground-breaking clinical trials for patients.
Further information, including patient information booklets, is available from http://www.beatingbloodcancers.org.uk
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