How is acute lymphoblastic leukaemia diagnosed?

Dr Karen Gunther, a clinical haematologist, explains how acute lymphoblastic leukaemia is diagnosed.

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Acute lymphoblastic leukaemia (ALL) is a malignancy of immature lymphoid cells. These live in the lymph glands, circulate in the blood, and stay in the bone marrow which is the “factory” where blood is made. 

Acute lymphoblastic leukaemia and lymphoma are overlapping clinical presentations of the same condition. The diagnosis depends on whether there is a marked increase in the peripheral lymphocyte counts in the blood or predominantly an increase in size of multiple lymph glands. 

Patients with acute lymphoblastic leukaemia generally present with features due to extensive bone marrow infiltration. This results in an associated loss of production of normal blood cells and low blood counts including anaemia, neutropenia (low counts of good white cells called neutrophils) and thrombocytopenia (low platelet counts). 

Anaemia leads to fatigue and tiredness, neutropenia leads to severe infections, and thrombocytopenia can lead to bleeding or bruising. 

Patients will often also have an enlarged liver or spleen and lymph glands (hepatomegaly, splenomegaly and lymphadenopathy). This particular kind of malignancy can often also involve the central nervous system. 

Diagnostic tests for acute lymphoblastic leukaemia

The white cell count in the peripheral blood may be reduced normal or markedly elevated depending on the primitive cells in the peripheral blood. Looking at the peripheral blood smear (technique to examine red and white blood cells and platelets under a microscope) can usually be used to recognise the abnormal cells with a uniform appearance and scanty cytoplasm in the peripheral blood. 

Confirmation of the diagnosis requires immunophenotyping. This is a process to identify the proteins presented on the surface of the cells and can be done by a technique called flow cytometry. This can be done on the peripheral blood, on a lymph node biopsy, or from a bone marrow aspirate and trephine biopsy. Patients suspected of having acute lymphoblastic leukaemia or lymphoma are usually worked-up by looking at a peripheral smear, bone marrow aspirate and trephine biopsy, and CT scans. 

The diagnosis requires identification of primitive lymphoid cells (lymphoid blasts with a characteristic immunophenotype) in the blood or bone marrow or other involved tissue. Lymphoblastic cells can be B cells or T cells. T-cell acute lymphoblastic leukaemia usually carries a worse prognosis. 

Differential diagnosis

All cases are classified according to the WHO classification based on B and T cell expression and associated genes that are expressed, such as the Philadelphia chromosome which can be present. 

The differential diagnosis includes other types of leukaemia and lymphoproliferative disorders. It’s essential to specifically identify the cells involved and exclude a reactive process which can result in similar findings, although immunophenotypically and genetically there is a significant difference. 

The prognosis is dependent on the patient’s age, race, white cell count, sex, genetic features and exact nature of the malignant cells. 

Treatment path

For optimal treatment, it’s important to adhere to contemporary research protocols as the treatment is improving over time. Patients need to be fully evaluated before treatment and monitored carefully during treatment. 

Treatment involves induction therapy usually with regimens involving multiple chemotherapeutic agents and often combinations with immune therapeutic agents, such as antibodies. 

Consolidation involves recurrent cycles of therapy usually again chemo-immunotherapy and often in high-risk patients going on to allogeneic haemopoietic stem cell transplant.

Intercurrent central nervous prophylaxis is involved in many of the treatment regimens and many of them also include maintenance therapy. It’s usually better to adhere to one of the well-tried and tested protocols rather than to mix and match between them. 

Full details regarding the leukaemia are required in order to optimise therapy and add specific agents which may add value in certain settings. Unfortunately, many of the additions to therapy which improve the outcome are extremely expensive and not necessarily routinely available. 

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