Leukaemia

Overview Leukemia is a common malignancy in children and adults that occurs when alterations in normal cell regulatory processes cause uncontrolled proliferation of hematopoietic stem cells in the bone marrow.

Definitions
Leukaemia: Clonal proliferation of hematopoietic stem cells in the bone marrow
Acute Leukaemia: Clonal proliferation of hematopoietic stem cells in the bone marrow that develops rapidly, requires immediate treatment and often presents with symptoms. In acute leukaemia the cells in the bone marrow are immature (blasts).
Chronic Leukaemia: clonal proliferation of hematopoietic stem cells in the bone marrow that develops slowly, treatment may be delated and often presents asymptomatically. In chronic leukaemia the cells in the bone marrow are still able to mature.
Lymphoma: Heterogeneous group of haematological neoplasms, characterised by proliferation of malignantly transformed T or B lymphocytes. The proliferation occur typically in the lymph nodes unlike leukaemia which occir in the bone marrow and result in overcrowding.

Watch Video An introduction to Haematopoesis

Classification

Its important to know that Leukaemia can be divided into acute and chronic and then further divided into its cell lineage. Remember that this makes each of them very different diseases.

Acute leukaemia
- Acute Myeloid leukaemia (adults)
- Acute Lymphoblastic leukaemia (children)
Chronic Leukaemia
- Chronic Myeloid leukaemia (adults)
- Chronic Lymphoblastic leukaemia (older adults)
Myelodysplastic syndromes
Leukemoid reaction

Remember Acute lymphoblastic leukemia occurs more often in children, whereas the other subtypes are more common in adults.

Clinical Presentation

Acute Leukaemia – pancytopaenia
- Acute Lymphoblastic Leukaemia (more common in children)
  - Fever
  - Lethargy
  - Bleeding
  - Hepatomegaly
  - Splenomegaly
  - Lymphadenopathy
  - Bone pain

Remember Patients will AML fall ill suddenly and deteriorate fast, because of Infection, Bleeding (low platelets) and Hyperviscosity.

Acute Myelogenous Leukaemia
- Constitutional symptoms: Fever, Weight loss, Night sweats
- Anaemia symptoms: Shortness of breath, chest pain
- Thrombocytopaenia symptoms: excessive bruising, nosebleeds, or heavy menstrual periods in women
- Less likely: Bone pain, hepatomegaly and splenomegaly

Causes of Panytopaenia

Bone marrow failure – Aplastic anaemia

Drugs

Bone marrow infiltration – Lymphoma, leukaemia, myeloproliferative disease, myelodysplastic

Hypersplenism

SLE

Sepsis

Alcohol

Radiation

Chronic Leukaemia – white cell count is high (but nonfunctioning)
- Chronic Lymphoblastic Leukaemia (more common in older adults)
  - 50% are asymptomatic
  - Hepaosplenomegaly
  - Lymphadenopathy
- Chronic Myelogenous Leukaemia
  - 20% are asymptomatic
  - Splenomegaly

SUMMARY OF MAJOR LEUKAEMIA
Subtype	Description	Typical Group affects
Acute lymphoblastic leukaemia	Blast cells on peripheral blood smear or bone marrow aspirate	Children (53% <20yo)
Acute Myelogenous leukaemia	Blast cells on peripheral blood smear or bone marrow aspirate; Auer rods on peripheral smear	Adults
Chronic lymphoblastic leukaemia	Clonal expansion of at least 5,000 B lymphocytes per μL (5.0 × 10⁹ per L) in the peripheral blood	Older adults (85% >65yo)
Chronic Myelogenous leukaemia	Philadelphia chromosome (BCR-ABL1fusion gene)	Adults

Investigations for Leukaemia

Bone marrow aspirate
Bone marrow biopsy
Cytogenetic testing
Flow cytometry with immunophenotyping
Molecular testing
Peripheral smear

Treatment

A patient with suspected leukemia should be referred to a hematologist-oncologist to confirm the diagnosis and initiate treatment.
Treatment depends on type of leukaemia

Complications of Leukaemia

Tumour Lysis Syndrome
Disseminated Intravascular Coagulopathy – Widespread activation of coagulation, from release of procoagulants into the circulation with consumption of clotting factors and platelets, with ↑risk of bleeding
Hyperviscosity
Death