Types Of Leukaemia In Children

Introduction

Leukaemia isa form of cancer affecting the blood and bone marrow. It is a complex and devastating disease that can affect individuals of all ages but children are particularly vulnerable. Childhood leukaemia is a broad term that encompasses various types of leukaemia specific to the paediatric population. This article will be exploring the most common types of leukaemia in children, highlighting their characteristics, symptoms, and treatment options.

Acute lymphoblastic leukaemia (ALL)

Acute Lymphoblastic Leukaemia (ALL) is the most prevalent type of leukaemia in children, makingup to 25% of cancers in children under the age of 15.¹ It originates in the bone marrow (spongey material inside bones), where lymphoblasts (immature white blood cells) become abnormal and multiply rapidly, crowding out healthy cells. The exact cause of ALL is unknown, but certain genetic factors such as family history and environmental exposures (i.e. benzene and ionising radiation) may contribute to its development.² 

Symptoms

The  symptoms of ALL may include: 

• Fatigue, weakness
• Fever
• Easy bruising or bleeding
• Frequent infections
• Enlarged lymph nodes

Diagnostic procedures

There are a variety of diagnostic procedures that are conducted when diagnosing ALL. These include: 

• Physical Examination —hecking for physical signs of the condition such as swollen glands
• Blood Sample — To identify the presence of high numbers of white blood cells
• Bone Marrow Biopsy — to check for the presence of cancer cells

Further testing may also be conducted to determine the progress and extent of the leukaemia. These include:

• Immunophenotyping
• Cytogenetic testing
• Lymph node biopsy 
• CT scans 
• Chest X-ray 
• Lumbar puncture

Treatment options

There are a variety of treatment options available for ALL. ALL usually develops quickly therefore treatment and intervention will begin swiftly post-diagnosis. 

Chemotherapy 

Chemotherapy is a medicine used to kill cancer cells. The chemotherapy treatment known as methotrexate is often used in ALL, usually administered via the veins 

Stem cell transplantation

Damaged blood cells are replaced with healthy ways, often from a donor. It is often used following high-dose chemotherapy that has been unsuccessful, however finding a donor match can be difficult 

Targeted therapy

Around 20-30% of ALL suffers have Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) — where the Philidelphia chromosome is present in leukemia cells. which affects around 20 to 30% of people with acute lymphoblastic leukaemia).  A targeted therapy known as imatinib can be used to treat Ph+ ALL. It is administered in tablet form and blocks growth signals in cancerous cells, killing them. Alternatives to imatinib that have the same effect include dasatinib and ponatinib.

Other therapeutic measures that may be used include radiotherapy, immunotherapy, steroid therapy, and certain experimental therapies that can be under clinical trials.

Prognosis and long-term outcomes

Due to improved diagnostic measures and treatment options available, the prognosis for ALL in children is generally positive with 5-year survival rate being around 90% in children diagnosed under the age of 15 and 75% in adolescents.

Despite a good prognosis, there are some long-term effects because of treatment such as chemotherapy. These include: 

• Secondary cancers 
• Cardiovascular disease 
• Peripheral neuropathy 
• Reduced bone density 
• Hepatic (kidney) dysfunction 
• Visual changes 
• Obesity and metabolic syndrome 
• Infertility and hormonal disturbance 
• Neurocognitive changes

Managing Side Effects

Ways to Manage side effects include: 

• Reducing the risk of infection by limiting contact with anyone who is sick 
• Good hygiene practices 
• Healthy diet and exercise
• Managing stress levels 
• Managing your temperature if you have a fever

- Seeking medical attention if you have any strong symptoms such as nausea, vomiting, fever, abdominal pain, shortness of breath, or dizziness

Some patients may remain immunocompromised because of chemotherapy and may be required to be put on immunosuppressants lifelong as a preventative measure to avoid the risk of infection. 

Acute myeloid leukaemia (AML)

Acute Myeloid Leukaemia is another type of leukaemia seen in children. Though it is less common than ALL, it still makes up nearly 25% of leukemias among children and teens. AML tends to be more common during the first couple of years of life and during the teenage years and occurs equally among boys and girls across all races.

AML affects myeloid cells, which are cells that later develop into red blood cells, platelets, and certain types of white blood cells. The cause of AML in children remain unclear, but certain genetic disorders, exposure to radiation or chemicals, and previous chemotherapy treatments are known risk factors.

Symptoms

The symptoms of AML include: 

• Fatigue
• Shortness of breath
• Pale skin
• Easy bruising or bleeding
• Recurrent infections
• Bone and joint pain

Diagnostic procedures

The diagnostic procedures that are conducted when diagnosing AML are largely the same as ALL and are detailed above.

Treatment options

There are a variety of treatment options available for AML. AML usually develops quickly therefore treatment and intervention will begin swiftly post-diagnosis. 

ChemotherapyChemotherapy is a medicine used to kill cancer cells. AML is treated with with a combination of two or more chemotherapies, administered via the veins. Treatment can be very intensive and require blood transfusions and antibiotics.

Non invasive chemotherapy

If a patient is deemed as not fit enough to withstand intensive treatment, non-invasive chemotherapy may be offered as an alternative.

Additional medications

After chemotherapy, additional medications such as all trans retinoic acid (ATRA) and arsenic trioxide may also be given to prevent the cancer from returning, however, it is important to note these have been known to include strong side effects such as bone pain, nausea and headaches.

Stem cell transplantation

Damaged blood cells are replaced with healthy ways, often from a donor. It  is often used following high dose chemotherapy that has been unsuccessful, however finding a donor match can be difficult.  

Targeted therapy

Targeted therapies may be offered for certain types of AML that are administered in tablet or intravenous form and blocks growth signals in cancerous cells which, in turn, kills them.

Other therapeutic measures that may be used include radiotherapy and certain experimental therapies that can be under clinical trials.

Prognosis and long-term outcomes

Due to improved diagnostic measures and treatment options available, the prognosis for AML is generally positive with 5-year survival rate being around 68% in children and adolescents.

Although the prognosis is positive, there are some long-term effects because of treatment such as chemotherapy. These include: 

• Secondary cancers 
• Bowel changes 
• Effects on bone marrow 
• Parotitis  
• Changes in taste and smell 
• Risk of infection 
• Obesity and metabolic syndrome 
• Infertility and hormonal disturbance 
• Seizures

As with ALL, there is support available to manage the potential effects of AML treatment.

Chronic myeloid leukaemia (CML)

Chronic Myeloid Leukaemia (CML), like AML, is characterised by the abnormal growth of myeloid cells but progresses much more slowly. It is relatively rare in children, affecting only around 2-3% of children under 15 and 9% of adolescents. CML is caused by a genetic mutation known as the Philadelphia chromosome.⁴

Symptoms

The symptoms of CML include: 

• Fatigue
• Weight loss
• Night sweats
• Abdominal discomfort
• An enlarged spleen

Diagnostic procedures

The diagnostic procedures that are conducted when diagnosing CML are largely the same as ALL, detailed above.

Treatment options

The main treatment options available for CML are:

Tyrosine kinase inhibitors (TKI)

TKIs are targeted therapies that switch off the ‘BCR-ABL1 gene’ in the leukaemia cells. This gene is present in cancerous myeloid cells because of the Philadelphia chromosome and aids the cancer to grow and multiply. Examples of TKIs used are Imatinib, Nilotinib, Dasatinib, Bosutinib, Ponatinib, and Asciminib. These may be used alone or in combination with one another. 

Stem cell transplantation

Damaged blood cells are replaced with healthy ways, often from a donor. It is often used following high-dose chemotherapy that has been unsuccessful, however finding a donor match can be difficult.

Prognosis and long-term outcomes

Like ALL and AML, the prognosis for CML in children is generally positive with 5-year survival rate being around 90%.

However, some long-term effects of treatment for CML include:⁵ 

• Cardiovascular problems 
• Pulmonary disorders 
• Gastrointestinal issues 
• Endocrine toxicities
• Secondary malignancies

Supportive care and managing side effects

As with ALL, there is support available to manage the potential effects of AML treatment.

Juvenile myelomonocytic leukaemia (JMML)

Juvenile Myelomonocytic Leukaemia (JMML) is an extremely rare form of leukaemia that typically affects children under the age of four. JMML is characterised by the uncontrolled growth of myelocytes (precursor cells to neutrophils, the largest class of white blood cells) and monocytes (a type of cell that boosts immune response) in the bone marrow. The exact cause is unknown, although certain genetic mutations, such as those associated with Noonan syndrome, have been identified.

Symptoms

The symptoms of JMML include: 

• Anaemia
• Fever
• Poor appetite
• Skin rash
• An enlarged spleen or liver 

Diagnostic procedures

The diagnostic procedures that are conducted when diagnosing JMML are largely the same as ALL, detailed above.

Treatment options

The treatment options available for JMML include high-dose chemotherapy to kill cancer cells as well as normal bone marrow and immune system cells, followed by stem cell transplantation to rebuild a healthy blood supply and immune system.

Other therapeutic measures that may be used include immunotherapy to boost the immune response to the cancer cells and molecular-targeted therapies to slow the growth of cancer cells. Prognosis and long-term outcomes

Around 50% of children with JMML who are treated with stem cell transplantation reach long-term remission, however, relapse rates are at around 35-40%.

Some long-term effects of treatment of children with JMML include: 

• Fluid retention
• Increased susceptibility to infections
• Osteoporosis

Supportive care and managing side effects

Managing the side effects because of long-term outcomes include: 

• Preventing infection by reducing the risk of infection by limiting contact with anyone who is sick and maintaining good hygiene practices
• Healthy diet and exercise, no smoking or drinking 
• Seeking medical attention if you have any new strong symptoms and keeping up to date with doctor follow-ups

Summary

Leukaemia in children encompasses a range of different subtypes, each with its unique characteristics and treatment approaches. Early diagnosis, effective treatments, and ongoing research efforts have significantly improved the prognosis for children with leukaemia. However, further advancements are still needed to enhance therapeutic options and minimise long-term side effects. A comprehensive understanding of the types of leukaemia in children enables healthcare professionals to tailor treatment plans and support families through this challenging journey, ultimately striving for better outcomes and improved quality of life for these young patients.