Acute lymphoblastic leukaemia (ALL)

Classification according to ICCC : I.a (Lymphoid leukemias)

Definition

Acute lymphoblastic leukaemia (ALL) is a malignant clonal disorder of the bone marrow characterised by a proliferative disorder of stem cells, which is due to a genetic defect in the nucleus of a stem cell.

Occurrence

Acute lymphoblastic leukaemia (ALL) is the most common malignancy diagnosed in children. Leukaemias represent 30% of all childhood cancers, out of which ALL accounts for 85%. The incidence rate is about 4.5 cases per 100,000 children per year.

Symptoms

Symptoms of acute lymphoblastic leukaemia involve pain in limbs, fever, bleeding into the skin and mucous membranes, lymphadenopathy, skin infiltration (particularly in newborns and young infants), hepatosplenomegaly. Neurological finding, infiltration of lacrimal glands, infiltration of testes might also be present.

Diagnosis

Basic information about the diagnosis is obtained from the examination of blood count, which typically involves anaemia, thrombocytopenia, leucocytosis or even leucopenia. Precursor cells might be absent in the differential.

Biochemical changes involve:

  • high CRP, FW
  • hyperuricaemia
  • hyperphosphataemia
  • elevated liver enzymes
  • potential X-ray changes in bones
  • infiltration of thymus (in case of T-ALL diagnosis)

Examination of bone marrow aspiration is crucial for the diagnosis: bone marrow from patients with acute lymphoblastic leukaemia is infiltrated (often uniformly) with cancer cells – lymphoblasts, which are subsequently characterised by cytochemical, cytometric, cytogenetic and molecular genetic methods. The individual characteristics of a malignant clone, which is obtained by a molecular genetic examination, is used to monitor the effect of treatment: the minimal residual disease (MRD) determines the quality of achieved remission, the intensity of further treatment, as well as the indication for stem cell transplantation.

Classification

Acute lymphoblastic leukaemia (ALL) develops in B-lymphocytic or T-lymphocytic cell populations at various stages of maturation of cell precursors. According to the basic morphologic classification, young precursors are classified as L1, L2 and L3 lymphoblasts. Furthermore, lymphoblasts are characterised by the presence of a non-accidental chromosomal aberration. The cancer cell is defined in more detail by a fusion gene (product of this aberration) detected by molecular genetic methods; the fusion gene determines the risk level of the disease, its prognosis and the intensity of further treatment. ALL in infants and bcr/abl positive ALL are treated according to a specific protocol.

Therapy

Chemotherapy is the basic treatment method. The most commonly used cytostatic drugs involve vincristine, anthracyclines, corticosteroids, and antimetabolites such as 6-mercaptopurine and methotrexate. These drugs are included in internationally recommended treatment protocols, the results of which are continuously assessed, and the protocols are updated. BFM protocols – and procedures derived from them – are nowadays uniformly used in the Czech Republic. Actinotherapy of CNS is used for patients in which a leukaemic infiltration of cerebral meninges was established at the time of diagnosis.

Approximately 10 to 12% of patients with ALL are reported to relapse (early relapse, late relapse, bone-marrow relapse, CNS relapse, testicular relapse). Most of these patients, however, can be further treated in accordance with relapse chemotherapy protocols, and potentially with a subsequent allogeneic transplantation of stem cells.

Treatment outcomes

Long-term survival of patients with acute lymphoblastic leukaemia (ALL) has improved significantly over the last three decades: about 85% of children with ALL can be cured nowadays. Treatment outcomes for ALL in infants are not so good: although the 5-year survival has improved, it is currently only about 40%.

Role of general paediatrician

The general paediatrician plays a crucial role in the diagnostic process, considering the eventuality of acute lymphoblastic leukaemia (ALL), and referring the patient to a haemato-oncological centre. In the course of treatment, which is usually provided on an outpatient basis, the general paediatrician cooperates with the centre and follows up the patient. He/she also treats febrile neutropenia during the maintenance therapy, and deals with the social issues of the patient and his/her family. Vaccination of paediatric patients with ALL is performed in vaccination clinics.