Childhood acute lymphoblastic leukaemia
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Dr. Susana Rives. Pediatrician specialising in hematology at the Hospital Sant Joan de Déu, Barcelona
What is leukaemia?
Leukaemia is a kind of cancer that affects the blood cells and the bone marrow. Children with leukaemia have many immature leukocytes, or white blood cells, and these prevent the production of normal leukocytes and other blood cells (leukocytes, red blood cells and platelets).
What is the bone marrow? What kinds of blood cells are there?
Leukaemias have their origin in the blood stem cells found in the bone marrow, which is the red spongy part inside the bones. In a healthy child the blood stem cells can be of two sorts, lymphoid and myeloid, and when they mature they give rise to the different kinds of blood cell, which are:
1) Red blood cells: these are the cells that transport oxygen from the lungs to the cells in the rest of the body.
2) Leukocytes, or white blood cells: these are the cells that help combat infections. There are various kinds of leukocyte such as neutrophils, monocytes and lymphocytes.
3) Platelets: these are the cells that help the blood to coagulate to control bleeding.
What kinds of leukaemia are there?
Leukaemias can be acute or chronic. Chronic leukaemias tend to affect adults, and on very rare occasions, children. Most childhood leukaemias are acute and can be of two kinds: lymphoblastic or myeloblastic.
Acute myeloblastic leukaemia has its origins in the myeloid stem cells (myeloblasts). Acute lymphoblastic leukaemia has its origins in the lymphoid stem cells (lymphoblasts). In both cases the leukaemia cells occupy the place of normal blood cells (leukocytes, red blood cells and platelets) and they can consequently give rise to infections, anemia (low levels of red blood cells) and bleeding.
What is acute lymphoblastic leukaemia?
Acute lymphoblastic leukaemia (ALL) is a cancer formed by immature lymphocytes, known as lymphoblasts. These cells prevent the growth all the other blood cells. ALL is the most frequent childhood cancer.
Lymphocytes are a kind of leukocyte, or white blood cell, and they can be of two sorts, B and T. Depending on whether the lymphoblasts have their origin in B or T cells the ALL is called ALL- B or ALL- T.
What causes acute lymphoblastic leukaemia?
The exact causes of ALL are not known. Research in this field is it important and more knowledge is being in gained about the genetic changes that occur in leukaemia cells. Nevertheless, the factors contributing to, and the causes of, most childhood ALL are unknown.
A minority of children do have some genetic disorders that predispose them to developing ALL. This is the case with children with Down syndrome or other syndromes such as Li-Fraumeni syndrome, ataxia–telangiectasia syndrome, and others. Other factors that increase the possibility of developing leukaemia include exposure to radiation prior to birth (X-rays), and having been administered chemotherapy for another cancer.
The siblings of a child with leukaemia have a slightly increased risk of developing the disease in comparison to other children. But this risk is very low, less than one in 1,000.
Leukaemia, like other kinds of cancer, it not contagious.
What are the symptoms of acute lymphoblastic leukaemia?
The production of normal blood cells becomes altered on account of the growth of leukaemia cells in the bone marrow. This can lead to:
-Fatigue and pallor (because of anemia)
-The appearance of bruises and small pink spots on the skin (petechiae) or others that bleed (because of low platelet count)
-Fever and infections that do not progress well (because of the poor functioning of the leukocytes)
-Pain in the joints and bones, limping (because of the invasion of the bone marrow by leukaemia cells)
-Lymphadenopathy, or the swelling of the lymph nodes (because of their occupation by leukaemia cells)
At the outset of the disease all these symptoms might appear to be the consequence of a viral infection. When the symptoms persist for more than 2-4 weeks, in most cases a diagnosis can be made. Since the symptoms are not specifically or exclusively associated with leukaemia, it is usually the case that a doctor will have been consulted on several occasions before diagnosis is sought. In general, this does not affect the child's options for a cure.
How is acute lymphoblastic leukaemia diagnosed?
In general, if the child presents the characteristic symptoms, leukaemia can be diagnosed by means of a blood test. The leukaemia cells can be seen by examining the blood under a microscope. Sometimes, at the outset of the disease, these cells can not be seen in the blood, but leukaemia is nevertheless suspected because of the symptoms, and because of some alterations observed in the blood test. Diagnosis is confirmed by means of bone marrow aspiration and biopsy (puncturing the crest of the ilium and analysing the cells obtained).
Figure: puncture and aspiration of the bone marrow from the hip (iliac crest) and examination of the bone marrow under the microscope. On the left, a healthy bone marrow and on the right, a bone marrow invaded by leukaemia cells
How is acute lymphoblastic leukaemia treated?
The aim of treatment for ALL is to eliminate the leukaemia cells to allow the bone marrow to return to its normal functions.
The child's hematologists will decide what the best treatment will be after considering many factors, amongst them being:
- the kind of ALL in question (B or T)
- the child's age and the number of leukocytes resulting from the diagnosis
- the genetic characteristics of the leukaemia cells
- the response to treatment
ALL treatment follow protocols drawn up by specialists in pediatric oncology and hematology, themselves based on other protocols (drawn up by groups in Spain and around the world).
Chemotherapy is the main treatment the child will receive. It consists of using drugs that eliminate cancer cells and impede their reproduction.
When chemotherapy is administered intravenously a special appliance, called a catheter, is used to avoid having to pierce the vein repeatedly. The catheter is introduced into a large vein and this makes it possible to administer all kinds of drugs, and to extract blood for blood tests, without having to repeatedly inject the child.
There is a kind of catheter called port-a-cath, which has a round reservoir compartment, made of metal or plastic, implanted under the skin of the thorax. The port-a-cath is very practical for children because, since it is implanted under the skin, it can't be pulled out and, furthermore, it is more difficult to infect than other kinds of catheter, and it enables the child to bathe
If chemotherapy is administered through a catheter, it reaches almost all the cells in the body via the blood. However, there are difficulties in delivering chemotherapy drugs to the cerebrospinal fluid found in the brain and spinal cord. That means leukaemia cells might survive in this fluid. In order to prevent the leukaemia cells that reach the cerebrospinal fluid from surviving, and then causing a relapse of the nervous system in the future, chemotherapy must be administered directly to the cerebrospinal fluid by means of lumbar puncture (intrathecal chemotherapy). For a small minority of children, whose ALL characteristics indicate that they have a heightened risk of relapse in the nervous system, this treatment may be supplemented with cranial radiotherapy.
Chemotherapy can cure up to 85-90% of children with ALL. When leukaemia cells can no longer be observed in the bone marrow, or anywhere else, the patient is said to be in complete remission.
15-20% of children may suffer relapse. Most relapses take place during the first five years from the time of diagnosis, especially during the first two years after treatment has concluded. In cases where there has been a relapse, chemotherapy is administered again and, depending on the case, a bone marrow transplant is performed (see ALL Relapse). There are also new forms of treatment for children who suffer a relapse (see New Treatments).
Most children with ALL have good chances of being cured with chemotherapy alone, and a bone marrow transplant is not indicated. A transplant is reserved for cases which are more difficult to cure just with chemotherapy because it is a more intensive treatment involving more risks and possible consequences.
In cases in which a child has suffered a relapse, or it is known that they have a heightened risk of relapse because of the characteristics of their leukaemia, a bone marrow transplant is indicated. The transplant is performed once complete remission has been achieved with intensive chemotherapy, or other forms of treatment. A bone marrow transplant increases the possibilities for a cure.
Kinds of chemotherapy
The kind of chemotherapy the patient will receive depends on the type of leukaemia and the patient's probabilities of relapse. There are three kinds of treatment that are more, or less, intensive, depending on the risk of relapse. Patients are classified into the following groups based on this risk:
1) Standard risk, 2) Intermediate risk, 3) High risk
The intensity and length of chemotherapy varies in accordance with the risk group. However, regardless of the group to which they correspond, all children being treated, will receive
1) An initial treatment, called induction therapy, of intensive chemotherapy, followed by
2) consolidation therapy or the intensification treatment, followed by
3) maintenance therapy which consists of low intensity chemotherapy in the form of tablets, meaning that in most cases the child can lead an almost normal life and go back to school, do sport and participate in other extracurricular activities. For a small group of children with a greater risk of relapse, instead of maintenance treatment, a bone marrow transplant is performed.
15-20% of children may suffer relapse. Most relapses take place during the first five years from the time of diagnosis, especially during the first two years after treatment has concluded. In cases where there has been a relapse, chemotherapy is administered again and, depending on the case, a bone marrow transplant is performed.
What are the chances of curing children with ALL?
Up to 85-90% of children with ALL can be cured. The probability of finding a cure can vary according to age (better between 1 and 9 years of age), the number of leukocytes from the diagnosis (better if the number is low) and the biological characteristics of the leukaemia (depending on the kind of leukaemia and the genetic alterations presented by the cancerous cells). Infants under the age of one year have a somewhat lower chance of finding a cure, as do other children with some genetic alterations, such as those with the Philadelphia chromosome. Nevertheless, with the new treatments available, most of the children in these subgroups are also cured. The factor that most influences the prognosis is the treatment administered and the response the patient presents to this treatment. Bone marrow aspiration and biopsies are performed throughout the treatment to evaluate this response.
What happens if the child has a relapse? What treatments are there for children with relapsed ALL?
If a child with ALL has a relapse, the chances of a cure, and the treatment, will depend on a number of factors, mainly:
1) the length of time between diagnosis and the relapse, the longer the better
2) whether it is a B- or T-type ALL
3) the location of the relapse (bone marrow or others such as the nervous system, testicles, etc.)
4) the response to treatment for the relapse
Treatment will generally consist of chemotherapy that is more intensive than the chemotherapy received initially and often, a bone marrow transplant. Some children who have had a relapse may be cured without receiving a transplant.
In recent years, as well as chemotherapy, there have been new treatments that may substitute or supplement chemotherapy, such as immunotherapy and treatments directed at molecular targets. (See New Treatments).
Over recent years there has been a revolution in the treatment of cancer and of ALL. Outstanding new treatments for ALL are known as precision medicine and immunotherapy.
Precision medicine consists of administering personalised treatment, targeting the genetic alterations present in a specific patient's cancer or leukaemia. For example, Imatinib has considerably increased the rate of cure for children suffering from ALL who have the Philadelphia chromosome (ALL Ph+).
Immunotherapy is a treatment that strengthens the body's immune system to enable it to better fend off cancer cells. There are various kinds of therapy, such as antibody drugs (rituximab, blinatumomab inotuzumab and others) and cell therapy. Amongst them, treatment with CAR T-cell therapy has had very promising results in children with B-cell ALL. CAR T-cells are lymphocytes collected from the patient and then genetically modified so that they recognise and destroy leukaemia cells.
When the treatment is over, the child will have regular check-ups with their hematologist and, if necessary, other specialists. These check-ups are carried out in order to detect any possible relapse, monitor progress, and treat any possible long-term complications. Over time the check-ups are further and further apart, until they occur just once a year. In the long term it is recommended to have a check-up at least once a year in order, at an early stage, to detect and if necessary treat, any consequences arising from the treatment or the leukaemia.
Recommendations and practical matters
We will now turn to some general recommendations in response to some of the most frequent questions raised by parents with children with leukaemia.
Will their hair fall out? When? Should we have it cut?
After the chemotherapy they receive to treat the leukaemia their hair will fall out. This usually happens two or three weeks after the start of the course of chemotherapy. If the child has long hair, it is best to cut it short before it starts to fall out. It is neither necessary nor appropriate from the psychological point of view, to have their hair cut during the first days in hospital. Neither is it necessary to explain that this will happen right at the beginning, but the child should be told about it before their hair starts to fall out. Their hair will start to grow again two or four weeks after having started the maintenance treatment phase during which the chemotherapy is of lesser intensity.
Given that the child will have reduced defences against infection because of the disease itself and also because of the treatment administered, good standards of bodily hygiene must be maintained as well as cleanliness in the hospital room, at home and with any toys.
Toys which accumulate a lot of dust are discouraged, as are cardboard boxes. Food should not be left outside the fridge. Plants in the room are prohibited because the soil contains fungal spores.
Keeping things neat and tidy helps the hospital's cleaning staff with their work.
It is advisable to keep the number of visitors in the room to a minimum because they might be carrying infections. It is recommended that there be no more than two accompanying visitors and that they wash their hands before entering the room. If any of the visitors is suffering from an infectious process (a cold, or conjunctivitis, etc.) it is best for them not to come.
Should this person be the mother, the father, or someone else who looks after the child and their presence is required, they should wear a mask and wash their hands before coming into contact with the child.
Children receiving intensive chemotherapy treatment must have a varied diet. When there is a low leukocyte count it is best to avoid raw foods that can not be peeled, such as lettuces, strawberries and tomatoes, etc.
Sometimes chemotherapy takes your appetite away or even causes nausea. On days when chemotherapy is being administered you should not try to force the child to eat because it can be counter-productive.
In contrast, the corticoids (prednisone and dexamethasone), which are administered in some phases of the treatment, can greatly increase the appetite and even cause related anxiousness. While it is perfectly acceptable to let them eat a little more than that which is served in the hospital, they should not be allowed to eat without measure, something that often does not agree with them, and which can cause stomach aches.
Links of interest concerning medical issues relating to childhood acute lymphoblastic leukaemia
For more quality information about childhood acute lymphoblastic leukaemia you can consult the following websites:
- Childhood acute lymphoblastic leukemia treatment. National Cancer Institute.
Links of interest about other general issues that may be of interest for patients with childhood acute lymphoblastic leukaemia
There are other resources and links of interest that may be of use to childhood acute lymphoblastic leukaemia patients:
- Bone marrow Transplant Guide. Fundación Josep Carreras
- Graft-versus-host disease. Leukaemia and Lymphoma Society
- Childhood Acute Lymphoblastic Leukemia treatment. NIH, National Cancer Institute
- Acute Lymphoblastic Leukemia. Leukaemia & Lymphoma Society
- About Acute Lymphocitic Leukemia (ALL). American Cancer Institute
Support and help
On our website you will also find the testimonies of people who are suffering, or who have suffered, from this disease. We would also like to invite you to follow us on our main social networks (Facebook, Twitter and Instagram) where we often share patients' accounts of overcoming the disease.
You can also check other interesting links here.
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You will find many other topics of interest about diet, fertility, treatments, etc., on our BLOG 'Unstoppable against leukaemia'.