Acute Leukemias

 

• Background

  

  
  

  Pathophysiology

  • Proliferation of immature blast cells. Aggressive cancer as, even before their oncogenic mutation, they have the capacity for self-renewal.
  • Acute lymphoblastic leukaemia (ALL): proliferation of lymphocyte progenitors.
  • Acute myeloid leukaemia (AML): proliferation of granulocyte progenitors. In some cases, follows myeloproliferative diseases (via myelodysplastic syndrome) including CML.

  Epidemiology

  • ALL: commonest childhood cancer, especially <5 years old, though 35% are >25 years old.
  • AML: risk increases with age. 1/20,000 annual incidence.
  • Both are slightly commoner in males.

• Signs and symptoms

  Cytopaenia due to bone marrow failure:

  • Anaemia: fatigue, pallor, SOB.
  • Infection. Despite ↑WBC, there is neutropenia. There may also be low grade fever even in the absence of infection.
  • Bleeding: bruising, menorrhagia, internal. May also be due to DIC.

  Organ infiltration:

  • Hepatosplenomegaly
  • Lymphadenopathy
  • CNS (especially ALL): CN palsy, papilloedema, meningism.
  • Testes (especially ALL): unilateral swelling.
  • Gum hypertrophy, skin nodules.
  • Thymus: mediastinal mass.

• Risk factors

  • Chemotherapy or radiation exposure.
  • Previous haematological disease (AML): myelodysplastic syndrome, paroxysmal nocturnal haemoglobinuria.
  • Family history.
  • Genetic: Down's (ALL), Fanconi's anaemia, ataxia telangiectasia.

• Investigations

  Bloods:

  • FBC: pancytopenia, though there may be neutropenia despite ↑WBC.
  • Coag: may show DIC.
  • Blood film: lymphoblasts in ALL, myeloblasts containing Auer rods in AML.
  • U&E: urea and creatinine may be ↑. Also may see ↑↓Ca2+, ↑K+, ↑uric acid.
  • LFTs may be ↑. This (and U&E) also needs to be checked as baseline before chemotherapy.
  • ↑LDH
  • Blood culture if there is fever.

  Organ infiltration:

  • Specific investigations such as CXR, CT, or LP.

  Diagnosis:

  • Bone marrow biopsy and/or aspiration, plus biopsy of infiltrated organs if possible.
  • Blast cells >20% confirms diagnosis.
  • Immunophenotyping to identify the subtype.
  • Cytogenetics provide prognostic and therapeutic information. Possible translocations: Philadelphia chromosome t(9;22) in adults with ALL, t(12;21) in kids with ALL, t(15;17) in acute promyeloid leukaemia (AML variant).

• Management

  Supportive:

  • Pancytopenia management e.g. RBC and platelet transfusion, antibiotics. Consider colony-stimulating factor if there is high risk of neutropenia.
  • Allopurinol if there is ↑uric acid from tumour lysis.

  Chemotherapy:

  • Duration: 6-8 months in AML, and up to 3 years in ALL.
  • AML: {cytarabine} plus {idarubicin or daunorubicin}.
  • ALL: many options. Imatinib if Philadelphia chromosome +ve.
  • May include intrathecal treatment for CNS disease.

  Stem cell transplant may be indicated in high risk patients.

• Complications and prognosis

  Iatrogenic complications:

  • Infertility, especially males, so sperm banking advised.
  • Nausea and vomiting.
  • Bone marrow failure.
  • Tumour lysis syndrome.
  • Long term risks: cancer, hypothyroidism, pulmonary fibrosis, heart failure.
  • Kids: short stature, ↓IQ

  Prognosis:

  • 5 year survival ALL: 90% kids, 50% adults.
  • 5 year survival AML: 20% overall, but 75% if age <60.
  • Poor prognosis if: old, adverse cytogenetics (e.g. t(9;22) in ALL, t(8;21) in AML), male (ALL in kids), ↑blast count, CNS disease.