Cancer is a group of rare diseases in children, each with a different name, characteristics, prognosis and specific treatments. In a healthy body, cells divide and multiply in an orderly manner. However, sometimes some of these cells gain the ability to divide and grow uncontrollably, as well as travel to any other part of the body, forming masses called tumours.

Malignant or cancerous tumours can invade, damage or destroy nearby tissues or organs and, through a process called metastasis, can release cancer cells that break away from the original tumor and reach other parts of the body.

Cancer can be located in different parts of the body (kidney, brain, muscles, bones, etc.) forming solid tumors. It can also be found in blood cells, bone marrow (leukemia) or in the lymphatic system (lymphoma).

In most cases, the cause of childhood cancer is still unknown, without being associated with lifestyles or environmental issues, as is sometimes the case with cancer in adults. In addition, on rare occasions, there is a family history of the same disease. All this makes these diseases challenging to diagnose, as well as to prevent in children.

Parents must not feel guilty or responsible for their child’s illness, because nothing they have done or failed to do has caused it to appear.

The cancer is not infectious; therefore, it is not spread by being in contact with the child.

Although leukaemia is considered a rare disease, it is the most common type of cancer affecting children.

Its origin is in the bone marrow of all the bones of the body, which is where blood cells (white blood cells, red blood cells and platelets) are made. White blood cells are responsible for protecting the body from infection and are part of the immune system.

Not all children and adolescents with leukemia have symptoms early in the disease. In addition, they can be few or many if they have them. They can easily be confused with the typical symptoms of other more frequent diseases such as the flu, mononucleosis, anemia, etc…

Symptoms can be tiredness, weakness, paleness, pain in the joints or bones, little appetite, fever, the appearance of frequent bruises without previous blow, swollen glands, spleen or liver, petechiae (round red dots on the skin), but also with more severe conditions of bleeding or infections.

If the doctor suspects leukaemia, they will perform a complete physical examination and a blood test to count the different types of blood cells and see their morphology. In addition, it will be necessary to carry out a bone marrow study through a puncture-aspiration (PAMO), usually in the hip bone. To rule out the presence of leukemia in the central nervous system, a lumbar puncture (LP) will be performed. The debut of leukaemia represents a medical emergency and patients should be referred to centres that have a medical service, and an experienced paediatric haematology-oncology laboratory.

Different types of leukemia are determined by the type of original white blood cell (lymphocyte or granulocyte) and by the molecular and genetic characteristics of these cells. Each type of leukemia receives a specific and different treatment, which is also modified according to its clinical response and other characteristics of the child, such as age and location of the disease (involvement of the bone marrow, testicles and central nervous system).

Currently. treatment protocols for each type of leukaemia have been developed cooperatively by groups of national and international experts. These protocols or treatment schemes have been modified and adapted to new knowledge to achieve the best possible results in terms of healing and with the least associated toxicity.

The main treatment for any type of leukemia is chemotherapy, although in some cases, a bone marrow transplant may be necessary, as well as radiotherapy.

In the first instance, the studies conducted to diagnose leukemia are the clinical examination and the analysis of blood/complete blood count.

In the second instance, bone marrow aspiration punctures are performed to evaluate and study the leukemic cells in the blood. Lumbar punctures are performed to assess their presence in the central nervous system.

Blood studies are performed periodically throughout the treatment to evaluate the evolution and effects of the treatment.

As for lumbar punctures, they are not only performed as a diagnostic study but also included in the treatment protocols as a regular practice to prevent the proliferation of leukemia cells in the central nervous system, administering intrathecal chemotherapy.

Leukemia treatment is divided into three phases:

• • Induction eliminates leukemia cells from the blood and bone marrow to enter remission.

• • Consolidation: its function is to eliminate the remaining cells that may persist.

• • Maintenance: this phase tries to destroy any cells that could have survived the previous treatment and prevent the disease from reappearing.

Chemotherapy

We call chemotherapy the combination of different drugs that have the ability to eliminate leukemia cells or prevent them from growing, dividing and acquiring the ability to make new cancer cells.

Like all medicines used in treating different diseases, chemotherapy can cause undesirable effects (adverse effects, alterations…) in other organs or functions of the body. For this reason, each chemotherapy has a particular way of being administered, trying to prevent, avoid or reduce the unwanted effects that it may produce. Suppose a medication has been proven to cause damage, for example, in the kidney. In that case, it will be administered with sufficient fluid intake to eliminate it more efficiently and without harming renal function.

The protocols combine the administration of chemotherapy agents, which can be given intravenously, orally or intramuscularly. In some treatment stages, both administration forms are used simultaneously, in others they are used alternately.

Radiotherapy

Radiotherapy is the use of high-energy radiation that has the power to destroy the ability of tumor cells to grow and reproduce.

The equipment for this treatment emits electromagnetic waves, just like the equipment used to take X-rays, but with greater power and intensity.

Unlike other types of cancer, radiotherapy is rarely used in leukemia. It is reserved only for bone marrow transplantation or local treatment of some leukemia lesions outside the bone marrow, such as the testicles. The radiotherapy doses are evaluated in each particular case and depend on different factors, such as the type of disease in question, the patient’s age and the treatment stage.

Technological evolution has allowed the development of increasingly precise devices for the application of this treatment, improving its effectiveness and avoiding possible subsequent damage to the patient’s health.

Bone marrow transplant

Bone marrow is the spongy tissue found inside some bones in the body, such as the hip or femur. It contains stem cells that can develop into red blood cells that carry oxygen within the body, white blood cells that fight infection, and platelets that help blood clot. It is what we commonly call the blood factory.

When we are in the presence of a disease such as leukemia, the blood factory produces abnormal cells that grow and multiply rapidly, preventing the development of healthy cells. The main treatment is chemotherapy, but sometimes a bone marrow transplant is considered. A bone marrow transplant is planned as a treatment option when the disease returns after some time pass or when the time it takes to eliminate the disease from the body exceeds what would be expected

Bone marrow transplant is the procedure by which the patient (recipient) receives a replacement of blood, bone marrow or umbilical cord cells from a compatible donor. These cells nestle in the receptor, grow, and become healthy blood cells that replace the ones the patient lost.

A matched donor is a healthy person whose specific characteristics of blood cells match those of the person who needs a transplant. Siblings from the same parents can be compatible donors, but unrelated people can be as well.

The medical team will determine the mosst suitable donor for each patient after conducting the necessary study and evaluations.

This way, we try to eliminate any possibility that the infused healthy cells could be affected by leukemic cells that prevent their development, and leave space for the new cells to nest and grow.

This period of preparation for the transplant lasts approximately seven days after which the donor cells are transfused, called day 1.

Within 15-28 days, you can begin to assess whether the procedure benefits the patient.

We could equate the procedure to a standard blood transfusion that is performed through a specially placed venous access. The most challenging things for the patient are the days before preparation and those until the new cells begin to grow, the conditions of extreme and prolonged isolation in a room specially conditioned to avoid any infectious complication, and the possible subsequent rejection reactions to the donated marrow.

As for the donor, their cells can be obtained by performing a bone marrow puncture or taking peripheral blood. In this second case, the donor must also go through a previous preparation consisting of stimulating factors that increase the bone marrow cell production and facilitates the pass into the blood circulation of the immature cells to be collected.

Focused therapies or targeted therapies

There are currently some targeted therapies under investigation. In some cases, drugs capable of attacking specific cancer cells without harming normal cells are already being applied.

Each disease requires a specific type of treatment and transplant, and not only the disease, but also the patient’s age and condition are critical factors.

Generally, a bone marrow transplant is only performed when it is the only possible curative alternative. In all cases, the indication for transplant must be made individually, assessing both the disease risks and the transplant potential risks and benefits, the disease status (if possible, the disease should be in complete remission), assuring that the patient’s organism will be able to withstand the treatment’s high toxicity, the presence of other associated pathologies and the degree of compatibility between the donor and the recipient.

Chemotherapy drugs can affect some normal cells in the body, causing side effects. The side effects will depend on the type and dose of drugs given, as well as the length of treatment.

These side effects may include:

• Hair loss
• Mouth ulcers
• Loss of appetite
• Diarrhea
• Nausea and vomiting

Chemotherapy drugs also affect normal cells in the bone marrow, and decrease blood cell counts. This can cause:

• Increased risk of infections (because there are too few normal white blood cells)
• Bleeding or bruising more often (because there are too few platelets)
• Tiredness or dizziness (because there are too few red blood cells)

Problems with blood cell counts are often caused by leukemia at first, but may worsen during the early part of treatment due to chemotherapy. The situation usually improves as the leukemia cells are killed and normal cells in the bone marrow recover.

During leukemia treatment, the main concerns for most families are the day-to-day issues. Once the treatment is completed, families’ concerns focus on the long-term side and the leukemia relapse.

Survivors of childhood leukemia are at risk, to some degree, for several potential late effects from their treatments. This risk depends on several factors, such as the type and subtype of leukemia, the type and dose of treatments received, and the child’s age at the time of treatment.

Broadly speaking, the side effects that all long-term medication can cause in children and adolescents treated to cure leukemia are:

Bone Problems

The use of corticosteroids can cause bone damage or osteoporosis.

Physical Effects

Children who are treated for leukemia or lymphoma are at risk for fatigue, growth retardation or smaller adult height, thyroid problems, hearing loss, and the development of secondary cancer. Children can also become sterile. The risk of infertility is related to the areas of the body that are affected by the cancer and the type, dose of radiation therapy, and the combination of therapy. Age at the time of treatment, gender, and genetic factors influence this risk.

On the other hand, certain chemotherapy or radiation therapy drugs can sometimes cause heart or lung problems later in life.

Learning Effects (cognitive)

Treatment including radiation therapy to the brain or some types of chemotherapy can affect the ability to learn in some children.

Learning difficulties may start during treatment or become apparent months or years after treatment. Math, spatial relationships, problem-solving, limited attention span, reading and spelling, information processing, planning and organization, and the ability to concentrate are all areas of learning that may be affected. There may also be problems with fine motor coordination, which can cause garbled handwriting.

Psychological Effects

Most childhood cancer survivors are in good psychological health.

However, some studies indicate that a small number of survivors of childhood leukemia or lymphoma were more likely than their healthy peers to have changes in mood, feelings, or behavior, including depression or post-traumatic stress disorder.

For this reason, the medical team must carry out a post-treatment follow-up, depending on the type of leukemia and the patient’s age, to detect any anomaly and treat it as early as possible.

For children, the most challenging aspect of treatment is many procedures (punctures, catheter fittings), which cause pain and discomfort, but are essential to carry them out.

It is essential to work with information appropriate to the age of each patient, the reason, intention and the importance of each procedure. It is also important to consider the educational level and the style in which family bonds and relates.

All children and adolescents need to know what is happening to them and what they will have to go through to regain their health.

Some families prefer that the information given by the treatment team; others prefer to be the ones who communicate to their children what will happen to them.

The information will give them confidence and reduce the anguish of facing what they do not know at first, avoiding unexpected situations.

We can help children by working with dramatization games or drawings about the procedure that will be carried out, where they will be able to express fears and fantasies, giving us guidelines on what aspects we should reinforce the information and what resources to offer them for its elaboration.

During the procedure we can help them with relaxation techniques, breathing techniques, music or whatever they choose to get through that moment. Having adequate information and the necessary resources allows them to choose, and sometimes the mere presence of one of their parents holding their hand is enough for them.

After the procedures, we can evaluate, both with the child and with their parents, how they felt, what things were uncomfortable for them and what things were positive for them,. Based on this,  we can think of new strategies for future procedures.

The role of parents in this process is essential. They are the ones who know their children best, they are their main support figures and they are the ones who can make decisions about some aspects of the treatment.

How children understand their disease and its treatment is directly related to how their parents experience it.

It may be useful to choose within the family group who is more prepared to accompany the child during the procedures without becoming distressed or expressing their own fears, giving them security and peace of mind.

In turn, the accompanying parent can help the child to communicate if something bothers him or causes him pain. The deep knowledge of his bond allows him to translate gestures and attitudes that it is difficult for the child to put into words.

Cure and remission

The concept of cure refers to the process and result by which a disease disappears.

That is, the patient can achieve remission of their disease in the first few weeks of treatment, but if they do not complete the treatment plan in its entirety, there is a high probability that the disease will reappear quickly.

We can speak of a cure when the complete remission of the disease transcends 5 years from its conquest.

Yes, a lot of research is being done on leukemia, because there are still many unanswered questions.

We can divide research into three types:

• Basic research: seeks to generate knowledge about the mechanisms of the disease, its biology and the mechanisms that generate it. It is usually based on specific laboratory studies with cell cultures and animal experiments.

• Translational research: facilitates the transition from basic research to clinical applications, from bench to bed-side, that is, from the laboratory to the patient’s bed. It is mainly based on applying new data and technologies for the patient’s diagnosis, monitoring and treatment.

• Clinical research: it is carried out directly on the patient, normally in the form of a clinical trial to see the efficacy and safety of new drugs, identify toxicities and apply new treatment protocols.

The ultimate goal of any childhood leukaemia research is to improve well-being and quality of life by eliminating leukemia in the most effective and least toxic way possible. There is research on:

• Improving biological knowledge about leukemia
• Refining the diagnosis, to adjust the treatment’s intensity to the patient’s risk of relapse, improving survival and avoiding toxicities
• Improving monitoring and detection of residual disease that may remain after administering treatment
• Improving treatment and toxicity

Therefore, different research projects may have different objectives. Thus, in a clinical research project, the objective may be to find out the most effective and, at the same time, least toxic combination of drugs. In another project you may want to compare which technique best detects very low levels of leukemia during treatment.

Likewise, a basic research project can try to decipher the mechanism by which some patients respond to treatment and others do not, to design a more effective targeted treatment.