Leukemia in children: types, symptoms, cure

Next to 500 cases of leukemia are diagnosed in children each year in France. They represent 29% of the 1,780 new cancer cases diagnosed in children under 15 years of age. Childhood leukemias are the most common cancers common in children. What are the causes ? What are the symptoms of pediatric leukemia? And the chances of recovery?

Definition: what is childhood leukemia?

Childhood leukemia results from a abnormality in the development of hematopoietic stem cells from the bone marrow (precursor cells of all blood cells: red and white blood cells, platelets). These stem cells can evolve into two main types of cells:

► The lymphoid stem cells, which then turn into lymphocytes (types of white blood cells). Three types of lymphocytes exist: B lymphocytes, T lymphocytes and NK lymphocytes;

► The myeloid stem cells, which produce red blood cells, other types of white blood cells (granulocytes, monocytes) and platelets.

Leukemias constitute a particular cancer, because the tumor cells invade the whole body from the bone marrow, through blood circulation.

What causes leukemia in children?

In more than 90% of cases, the causes of acute lymphoblastic leukemia (ALL) remain unknown. For the remaining 10%, the recognized risk factors are genetic Or toxic and related:

• to a genetic abnormality such as trisomy 21 (mongolism or Down syndrome),
• to exposure to certain toxic substances (benzene, heavy metals) and ionizing radiation

There are probably factors of genetic predispositionwhich are still being studied: the monozygotic twin (identical twin) of a child with leukemia is also at risk of developing this disease, especially if it occurs in the first year of life. “But it is in no way a transmissible genetic disease”, says Dr. Cécile Renard, pediatrician at the Institute of Pediatric Hematology and Oncology in Lyon.

What are the types of childhood leukemia?

We mainly encounter leukemias acuterapidly evolving, as opposed to chronic leukemias more common in adults. Depending on the type of white blood cells affected, we speak of:

• acute lymphoid leukemia (lymphoblastic) if lymphocytes (a type of white blood cell) are involved. Acute Lymphoblastic Leukemia (ALL) accounts for 80% of acute leukemias in children.
• acute myeloid leukemia (myeloblastic) (LAM) if cells of the myeloid lineage are involved (20%).

What are the symptoms of leukemia in children?

Acute leukemia occurs suddenly and is manifested by a bone marrow failure and the proliferation of abnormal cells, one being the result of the other. Bone marrow failure affects all three types of blood cells. We then observe:

• paleness, fatigue, breathing difficulties (dyspnea), palpitations (tachycardia) and general malaise, this is a sign of a lack of red blood cells (anemia),
• recurrent infections such as angina, bronchitis, gum infections (gingivitis), this is a sign of a lack of normal white blood cells,
• small bleeding in the thickness of the skin (petechiae), bleeding from the gums, nose, etc., this is a sign of a lack of platelets.
• a enlargement of the liver, spleen and lymph nodes,
• of the bone or joint pain, to the point that the child may begin to limp (these are due to the proliferation of leukemic cells in the marrow of the bones concerned).

It is rare for a child to present all of these abnormalities. They can often be reduced to one or two symptoms.

► Blood test. “A diagnosis of acute leukemia is often suspected following a blood test, or complete blood count (NFS), when this shows a anemiathrombocytopenia and neutropenia (drop in neutrophilic leukocyte count)”, continues the doctor. “This analysis often reveals the presence of leukemic cells, immature and abnormal white blood cells, called blasts.”

► Myelogram. However, a simple blood test is not enough to make the diagnosis, nor to determine the type of leukemia from which the child is suffering. A myelogram is required. This is an examination in which the morphology of bone marrow cells is studied under a microscope. The removal of these cells is carried out, by puncture in the sternum or in the bone of the pelvis. If this gesture only lasts a few minutes, it can nevertheless be painful.

► Other laboratory tests are essential to refine the diagnosis and prognosis. This is the case of the study of proteins present on the surface or inside the leukemic cells (immunophenotype). Various techniques make it possible to identify chromosomal (karyotype) or acquired genetic (molecular biology) abnormalities characteristic of leukemic cells. These different elements make it possible to specify the prognosis.

► Lumbar puncture. Finally, a lumbar puncture (also performed under local anesthesia associated with the inhalation of nitrous oxide) is essential to find out if leukemic cells have infiltrated the central nervous system.

What are the risk factors for leukemia in children?

Several risk factors for leukemia have been identified in children:

• I’existence of genetic syndromes (resulting from the mutation of one or more genes), in particular Down syndrome, Bloom syndrome, Fanconi anemia, ataxia-telangiectasia, neurofibromatosis type 1, Wiskott-Aldrich syndrome, Li-Fraumeni syndrome or Shwachman-Diamond syndrome;
• Of the history of leukemia in siblings;
• Exposure to strong radiation doses;
• Previous treatment with radiotherapy or chemotherapy;

Alongside these known factors, other aspects could play a role in the occurrence of leukemia, even if this link has not yet been scientifically proven: exposure to certain radiation or electromagnetic fields, pesticides, cigarette smoke, alcohol, benzene (carcinogenic solvent) or even maternal exposure to certain paintings.

What are the treatments for childhood leukemia?

To treat acute lymphoblastic leukemia in children, we use primarily chemotherapy. This treatment is conventionally divided into several stages:

► Induction. This is the initial phase of treatment. It aims to greatly reduce the amount of cancer cells. This is a relatively intensive treatment that lasts 3 to 4 weeks.

► Consolidation. It begins as soon as complete remission is achieved, ie the absence of symptoms and clinical signs (cancer cells are no longer detected in the blood or in the bone marrow). This phase of the treatment uses drugs different from those used during induction.

“The cure rate for leukemia continues to improve,”

► Intensification. It follows consolidation and usually resumes the medications used during induction.

“These treatment phases constitute the ‘heavy’ treatment, which lasts between 6 and 12 months, with consequences for family life and schooling, continues Dr. Rénard. Indeed, the child is often in the hospital and cannot go to school. Fortunately, the school at the hospital as well as many stakeholders are taking over to help the child and his family during this difficult period.”

► Maintenance treatment (in cases of acute lymphoblastic leukemia only). It aims to prevent a possible resumption of the disease and lasts about 2 years. When treatment is stopped, regular monitoring is carried out for several years, which consists of a medical examination and a blood test.

“The cure rate for leukemia continues to improve, thanks to better characterization of the disease by molecular biology techniques, and the detection of more resistant forms by monitoring the residual disease, reminds the specialist. Treatments are also improving, and new therapies (immunotherapy, CAR T-cell) develop for the most serious forms.” Research continues to advance and allow more patients to be cured, while trying to reduce the toxicities of treatments.

What is the cure rate for childhood leukemia?

The cure rate is nearly 90% for children with acute lymphoblastic leukemia and around 60% for acute myeloblastic leukaemia. We can speak of recovery from the 5 years of the diagnosis of acute leukemia, after which a relapse is exceptional. “Allograft bone marrow is rarely necessary in acute lymphoblastic leukemia and reserved for the most serious forms and relapses, concludes Dr Renard. This treatment is more often necessary in acute myeloblastic leukaemias”. A long-term follow-up study is currently underway in France (LEA = Leukemia Child Adolescent), and has shown that most adults treated in childhood for leukemia are doing well, but that certain organs are to be monitored more particularly in allograft patients.

Thanks to Dr Cécile Rénard, pediatrician at the Institute of Hematology and Pediatric Oncology of Lyon.