Haematological Malignancies: Leukaemia Types

Leukaemia

• Definition: Progressive proliferation of immature leucocytes (blast cell >20%) that diffusely infiltrate all organs and tissues, displacing normal haematopoietic cells from the bone marrow.
• Incidence: 1:10,000 for AML (80% of adult AL) and 1:70,000 for ALL (80% of children AL).

Etiology of Leukaemia

• Genetic: Down syndrome, Fanconi anemia
• Radiation
• Chemical: benzene
• Chemotherapy
• Viruses: EBV in ALL
• Previous haematological disorders: MDS, myelofibrosis, CML

Clinical Features

• Symptoms of bone marrow failure: anaemia, thrombocytopenia, neutropenia
• Tissue infiltration: lymph node enlargement, hepatosplenomegaly, CNS involvement, lung, gum hypertrophy, skin chloromas (monocytic AML), testicular infiltration (ALL)
• Leukostasis causes infarction
• Increased uric acid
• Bone pain

Acute Leukaemia

• Accumulation of blasts in the marrow >20%
• AML: tissue/organ infiltration, bone marrow cytogenetic for prognosis and treatment, immunophenotyping of blood or marrow blasts (CD19 for ALL, CD33 for AML)
• ALL: tissue/organ infiltration, central nervous system (CNS) involvement

Classification of AML

• FAB classification: M0, M1, M2, M3, M4, M5, M6, M7 based on predominant differentiation pathway and degree of differentiation.

Specific Treatment of ALL

• Remission induction: using vincristine, prednisolone, daunorubicin, and asparaginase
• CNS prophylaxis: cranial irradiation and intra-thecal methotrexate
• Consolidation therapy: 1-2 intensification phases to reduce the risk of relapse
• Maintenance therapy: 2-3 years of 6-MP and methotrexate
• Allogeneic stem transplant: an option in young patients with high-risk disease

Prognosis of ALL

• About 75% of adults achieve complete remission (CR) with modern therapy and good supportive care
• 5-year survival rate for children is around 70%
• For adults <30% (less than 20% for those <50 years)

Emergencies in Haematological Malignancies

• In acute leukaemia: DIC with severe bleeding (AML M3), severe thrombocytopenia with ICH, neutropenic fever and septic shock, tumour lysis syndrome and acute renal failure

Chronic Myeloid Leukaemia (CML)

• Definition: clonal disorder of pluripotent stem cells
• One of the myeloproliferative disorders (MPD) that forms 15-20% of all leukaemias
• Peak age of incidence: 40-60 years
• Incidence: 1.25/100,000
• 3 phases: chronic phase (blast 5-9%), accelerated phase (blast 10-19%), blastic phase (blast 20%)

Clinical Features of CML

• Asymptomatic, discovered accidentally
• Anaemia
• Abdominal discomfort due to splenic enlargement (splenomegaly in >75%), hepatomegaly
• Sweating, fever, weight loss, gout, leukostasis (infarction)
• Signs: pallor and splenomegaly that can be huge

Investigations for CML

• Peripheral blood: Hb N or ↓, Plt: N, ↑, or ↓, WCC: ↑ (usually above 50,000/cu mm but may reach up to 500,000), shows the whole spectrum of myeloid precursors with only few blasts
• Bone marrow: hypercellular with ↑ in myeloid series
• Cytogenetics: Ph chromosome (t 9-22) is present in most patients
• PCR for BCR-ABL fusion gene
• Increased ESR, LDH, uric acid, decreased NAP score (increased in infection)

Management of CML

• Imatinib (STI 571): first-line drug in chronic phase, causes major cytogenetic response in 83% of patients
• Chemotherapy: hydroxyurea, effective in controlling leucocytic count
• IFN-alpha SC: may produce cytogenetic response (decrease the % of Ph +ve cells), may be useful in pregnant
• Bone marrow transplant: only established curative treatment

Chronic Lymphatic Leukaemia (CLL)

• Definition: uncontrolled proliferation and accumulation of lymphocytes that are mostly mature but immunologically incompetent
• Incidence increases with age, median age: 65 years, incidence: 2.5/100,000

Clinical Features of CLL

• Often asymptomatic, detected accidentally
• May complain of recurrent infection, weight loss, manifestations of BM infiltration: anaemia, neutropenia, thrombocytopenia
• G. lymphadenopathy, moderate splenomegaly, hepatomegaly
• Autoimmune AIHA, ITP may occur

Investigations for CLL

• FBC and blood film: lymphocytosis > 5X 10^9/L, mature lymphocytes
• Anaemia, neutropenia, thrombocytopenia due to BM failure are usually absent in early stage, however, they can be caused by autoimmune mechanisms
• BM: lymphocytosis > 30% with characteristic immunophenotypic markers (CD5,23)

Treatment of CLL

• Indications to start treatment: anaemia, recurrent infection, bleeding, bulky disfiguring or compressing LNs, increasing splenomegaly
• Treatment: chlorambucil with or without prednisolone, prednisolone to control AIHA, sometimes radiation to relieve compression
• Stem cell transplant

This quiz covers the definition and types of Leukaemia, a haematological malignancy. It discusses the differences between chronic and acute Leukaemia, as well as myeloid and lymphatic types.