Acute lymphoblastic leukaemia

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Acute lymphoblastic leukaemia (ALL) is a malignant disease of the lymphoid cell line in the bone marrow. There is uncontrolled clonal cell proliferation which infiltrates the normal bone marrow and displaces the normal haematopoiesis. There is also extramedullary infiltration to CNS, liver, testes, and skin. There is at least 20% blast rate in bone marrow and/or peripheral blood, and the cells are proven to be of lymphoid origin.

It occurs mostly in children between ages 2-6 years, and 60% of the patients are younger than 20 years. However, it might occur in adults also, and the median age for adults is 35 years. More common in males.

Clinical features

General features of acute leukaemia (both AML and ALL) are characterized by subacute onset and rapid progression. They include:

  • Symptoms of anaemia
    • Fatigue
    • Pallor
  • Symptoms of thrombocytopenia
    • Epistaxis
    • Bleeding gums
    • Petechiae, purpuras
  • Frequent infections and fever due to immature leukocytes
  • Hepatosplenomegaly

Some present with oncological emergencies like tumour lysis syndrome or DIC.

Hepatosplenomegaly and lymphadenopathy are more common in ALL than AML. CNS and meningeal infiltration are common, causing headache, altered mental status, or other neurological symptoms. Infiltration of the bone marrow and periosteum can cause bone pain.

B-symptoms (fever, DRENCHING night sweat, unintentional weight loss >10% last 6 months) are common in ALL, but not AML. Testicular enlargement is a rare but significant finding of testicular infiltration.

Diagnosis and evaluation

Some cell lines may be normal at the time of diagnosis.

Diagnosis is confirmed on detection of >20% blasts in the bone marrow or finding specific genetic mutations on cytogenic examination (PCR). This requires a bone marrow aspiration and biopsy. If it’s not possible, a peripheral blood smear might be used.

Immunophenotyping is achieved with flow cytometry to determine the origin of the myeloid cell line. Immunophenotyping, molecular diagnostics, and cytogenic examination are important to determine the exact subtype, which is important for prognosis and to guide treatment.

Philadelphia translocation (t(9;22)) is present in 20-30 % of adults. PCR is also useful for confirming subtype. Lumbar puncture to check for CNS infiltration in addition to brain and spine CT or MRI. This should be done in all patients.

Treatment

The goal is to achieve and maintain complete remission, meaning that there is recovery of normal bone marrow function and <5 % blasts.

It takes nearly 2-3 years with treatment to reach complete remission. Induction therapy is usually with agents such as vincristine, doxorubicin, dexamethasone. This last for 4-8 weeks. Consolidation with methotrexate for 4-8 weeks. Maintenance by methotrexate weekly and 6-mercaptopurine daily for 2 years.

CNS prophylaxis is a must as the relapse rate is 60 % if not given. Intrathecal chemotherapy with methotrexate or cytarabine is given, and CNS irradiation might be considered in some cases too.

In case of relapse or high-risk disease, allogenic stem cell transplant is considered.

Same prophylactic therapy as in AML.

Prognosis

BCR-ABL1 positivity means very poor prognosis.

The prognosis is way better for children than for adults. Complete remission is 97 % for children, and 5-year survival is 80-90 %, while for adults 5-year survival is 35 %.