Acute leukaemias are malignant cells that either arises from lymphoid of myeloid cell lines. To understand the process of leukaemia we need to first understand the production of blood cells within the bone marrow. All blood cells are produced from a haematopoietic stem cell within the bone marrow, this can differentiate into a common myeloid progenitor cell which will then differentiate into platelets, red blood cells and some white blood cells (mast cells, basophils, neutrophils, eosinophil and macrophages). If the haematopoietic stem cell does not differentiate into a myeloid cell they produce a common lymphoid progenitor cell, which gives rise to natural killer cells, T cells and B cells, other white blood in the circulatory system.
Acute myeloid leukaemia refers to malignant neoplasm arising from the myeloid cell line and is mostly seen in adults. Whereas acute lymphoid leukaemia affects the lymphoid lineage and is the most common childhood malignancy. Both of these lead to rapid production of their cell line however due to the rapid turnover these are immature cells and do not function as they normally would, this also leads to a suppression of all other cell lines, resulting in anaemia, clotting disorders and increased susceptibility to infections. In acute lymphoid leukaemia (ALL) most commonly the B cells are affected. There is what is known as the two-hit hypothesis which assumes leukaemia is the result of two genetic mutations, the first being a clonal proliferation of the lymphoid or myeloid stem cells and the second mutation affects the normal haematopoietic differentiation. This results in the bone marrow filling with numerous immature non-functional cells. Leading to leukopenia (lack of immune cells, increasing risk of infection), thrombocytopenia (decreased functional platelets leading to decreased ability to form clots) and anaemia (lack of red blood cells to carry oxygen). This can give rise to classic symptoms such as fatigue, pallor, weakness, bleeding, hepatomegaly and/or splenomegaly and fever. ALL can give rise to painless lymphadenopathy as it affects the T and B cells which reside in lymph nodes around the body.
Treatment of these conditions involves aggressive chemotherapy and sometimes allogeneic transplantation, where stem cells are collected from a matching donor to be transplanted into the patient to restore their immune system and suppress the disease. There are 3 phases are part of the chemotherapy regimen:
1 – Induction therapy – the goal of this stage is to massively reduce the tumour cell count
2 – consolidation therapy – the goal is to destroy any remaining tumour cells. This phase lasts several months
3 – maintenance therapy – the goal is to maintain remission; which chemotherapy is given in low doses for up to 24 months.
Common induction chemotherapy agents used: vincristine (inhibits microtubule formation in the mitotic spindle preventing replication of cells), glucocorticoids, asparaginase (leukemic cells are unable to synthesis asparagine, a non-essential amino acid, like other body cells, asparaginase breaks down circulating asparagine so it cannot be used by leukemic cells).
Supportive therapy is extremely important as patients can be severely immunocompromised. Personal hygiene and providing a germ-free environment is key to help avoid infections.