All about acute lymphoblastic leukemia

10/01/2020

This cancer, that involves the bone marrow, affects a particular type of white blood cells, lymphoblasts (lymphocytes at an early stage of development). It is the most common leukemia in children, although it affects all age groups.

Like all cancers, acute lymphoblastic leukemia (ALL) is a disease characterized by the malfunctioning of certain cells of the body that multiply uncontrollably, first locally and then in nearby tissues. This form of leukemia is a rare disease that affects children more than adults, and men more frequently than women.1

The incidence (number of new cases during a given period in a given population) in children is 40 cases per million in European countries (the incidence is essentially the same in all developed countries). The incidence peak is located between 0 and 5 years2 in Europe and the United States.

Particularly aggressive, this form of leukemia is a diagnostic and therapeutic emergency. In the past ten years, medical advances and the introduction of new treatments have allowed remarkable progress in cure rates, mainly in children, who withstand chemotherapy better than adults.

90%
This is the cure rate in children in industrialized countries
1.28
The incidence rate of ALL in Europe in adults is 1.28 per 100,000 individuals per year
80%
In Europe, ALL makes up 80% of leukemias in children below the age of 15 years

Bone marrow, the producer of blood cells

Leukemia affects the bone marrow, the place where blood cells are produced. These cells include erythrocytes (red blood cells responsible for transporting oxygen), leukocytes (white blood cells that defend the body against infection), and thrombocytes (platelets, which aid in clotting).

Acute lymphoblastic leukemia affects stem cells that give rise to a particular type of white blood cells, lymphocytes. Instead of differentiating into mature cells and migrating into the blood, these “blasts” (abnormal cells that have not reached their maturity) proliferate in an unregulated manner. They invade the blood marrow and impede the normal production of blood cells. These blasts may also reach other organs, such as the lymph nodes, liver and spleen.

Risk Factors

ALL, which is neither contagious nor hereditary, has no known cause or triggering factor. In the majority of cases, it occurs in subjects who were previously in good health. However, several risk factors have been identified:

  • Exposure to ionizing radiation: accidental, therapeutic (radiation therapy), or occupational
  • History of chemotherapy, administered during a prior cancer
  • The presence of certain genomic anomalies, including Down syndrom
  • Pre-existing blood conditions

A treatment for bone marrow

This disease must be managed quickly. As the bone marrow is invaded by abnormal cells, death can occur following infections (as the consequence of a reduction in normal white blood cells) or bleeding (as a result of reduced platelet production). The care protocol is established by the hematologist-oncologist and relies on several phases of combination chemotherapy, which combines intravenous injections with oral treatments:

  • An induction treatment, with hospitalization for at least a month. This induces bone marrow aplasia, ie, a very substantial reduction in the number of blood cells. Its purpose is to eliminate cancerous cells, which will enable a normal regeneration of blood cells.

 

  • A consolidation treatment, a hematopoietic stem cell transplant (bone marrow transplant) is sometimes suggested. This transplant comes from a compatible donor (family, donor registry), but can also be obtained from placental blood, called cord blood.

  • To prevent relapses, an outpatient maintenance treatment is administered for two years.

 

  • Cancer cells can infiltrate into the meninges, the membranes that surround the brain and spinal cord. This neuro-meningeal involvement is a major cause of relapses in the first year of treatment. For prevention, patients receive cranial radiation therapy and/or a chemotherapy injection.

 

  • In the event of relapse, a new chemotherapy is prescribed, starting with a reinduction treatment, again followed by a maintenance and consolidation treatment. A hematopoietic stem cell transplant may also be considered, originating from healthy donors (allograft) or from the patient themselves (autograft).

New therapeutic approaches

While the response rates observed after standard treatments are generally high, some patients will resist or relapse. Research has shown that cancer cells can develop mechanisms for escaping the patient’s immune system, allowing them to not be recognized as dangerous. Cancer cells can thus proliferate in the patient’s body.

New therapeutic approaches are being studied, at different stages of development, to treat these patients. They can use the immune system in order to give it back the ability to eliminate cancer cells. These approaches include targeted therapies, mainly based on the use of specific antibodies for certain tumor cell markers, and immunotherapies.

And Servier?

Servier currently invests a large part of its budget in oncology research and development, with the goal of improving management of patients with hematological malignancies, especially acute lymphoblastic leukemia.

To better understand the mechanisms that lead to the development of the disease or to resistance to standard treatments, searching for new targets that may allow developing new therapeutic options and generating data for defining what treatment or treatment sequence may be the best suited to each patient are avenues currently pursued by the Group’s R&D teams.

KEY POINTS

  1. Acute lymphoblastic leukemia

    is a rare disease that especially affects children.
  2. Its cause is currently unknown

    and it does not present specific symptom.
  3. During the past few years,

    the management of this disease has made considerable progress leading to high cure rates, particularly in children.

1American Cancer Society – July 2019. SANTÉ PUBLIQUE France /INCa

2Parkin DM et a., eds. International incidence of childhood cancer, Vol. II. Lyon, International Agency for Research on Cancer – WHO Fact Sheet 2009

 

3Hunger SP, Mullighan CG. Acute Lymphoblastic Leukemia in Children. N Engl J

Med. 2015;373(16):1541-1552.

4Sant M, Allemani C, Tereanu C, De Angelis R, Capocaccia R, Visser O,Marcos-Gragera R, Maynadié M, Simonetti A, Lutz JM, Berrino F; HAEMACARE Working Group. Incidence of hematologic malignancies in Europe by morphologic subtype:results of the HAEMACARE project. Blood. 2010;116(19):3724-3734.

5Coebergh JWW, Reedijk AMJ, de Vries E, et al. Leukaemia incidence and survival in children and adolescents in Europe during 1978–1997. Report from the Automated Childhood Cancer Information System project. Eur J Cancer. 2006;42(13):2019-2036.