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Leukaemia means cancer of blood cells. It can be classified into two main categories: Acute Leukaemias and other types of Leukaemias. In this issue of HealthNews, we break down the types of Leukaemia and how advances in treatment are improving the survival outlook for patients with the disease.

Leukaemia is a type of blood cancer that occurs when the bone marrow—also known as the blood cell ‘factory’ in the body—produces abnormal blood cells that crowd out healthy cells and eventually enter the bloodstream. It is the 12th most common cancer and 10th most common cause of cancer deaths in Singapore¹.

There are many subtypes of Leukaemia, each with its own unique characteristics, prognosis, and treatment modalities. In general, Leukaemia can be classified into two main categories: Acute Leukaemia and other types of Leukaemias.

Acute Leukaemia is fast-growing and aggressive. It progresses rapidly, compared to other types of Leukaemia. The cancer cells originate from the immature blood cells. Acute Leukaemia can be categorised into two main subtypes, based on the type of white blood cell affected:

• Acute Myeloid Leukaemia (AML), which involves the overproduction of abnormal immature myeloblasts.
• Acute Lymphocytic Leukaemia (ALL), which involves the overproduction of abnormal immature lymphoblasts.

Other types of Leukaemia

• Chronic Myeloid Leukaemia (CML), where immature myeloid cells (cells responsible for producing red blood cells, platelets and certain white blood cells) undergo a genetic change that forms a genetic mutation called BCR-ABL, turning the cells into CML cells which grow and divide uncontrollably.
• Chronic Lymphocytic Leukaemia (CLL) occurs when the body produces an abnormally high number of B-cells (a type of white blood cell that fights infections) and crowds out healthy cells in the body.
• Other Leukaemias include Adult T-cell Leukaemia (associated with human T-lymphotropic virus infection), NK/T-cell Leukaemia (originating from NK/T cells of the immune system), Hairy Cell Leukaemia (a type of B-cell cancer), B/T-cell Prolymphocytic Leukaemia, Plasma Cell Leukaemia (originating from plasma cells), and Large Granular Lymphocytic Leukaemia.

Symptoms of Leukaemia

Leukaemia symptoms vary based on the subtype of Leukaemia. In general, common signs and symptoms of Leukaemia include:

• Fatigue
• Fever
• Breathlessness
• Pale skin
• Feeling weak
• Loss of appetite and weight loss
• Night sweats or excessive sweating
• Bleeding gums or nosebleeds
• Easy bruising
• Red or purple spots on the screen
• Bone or joint pain
• Frequent or severe infections

In the case of Acute Leukaemia, rapid production of leukaemia cells in the bone marrow may lead to rapid decline in the production of normal red blood cells, white blood cells, and platelets. This accounts for symptoms related to anaemia and low platelet count, such as fatigue, easy bruising and/or bleeding, fever, and infection.

Management of Leukaemia

Advances in cancer research and technologies over the last decade have led to new frontiers in the treatment of blood cancers, including Leukaemia. Today, Leukaemia can be managed by a wide array of treatment modalities, depending on the subtype of disease.

Treating Acute Leukaemia

In general, treatment for Acute Leukaemia is directed against leukaemia cells in order for normal red blood cells, white blood cells, and platelets to recover. Because of its aggressive nature, the management of Acute Leukaemia requires more intense and timely treatment compared to other Leukaemia subtypes.

Acute Leukaemia is usually treated with intensive remission-induction chemotherapy aimed at leukaemia cells in the bone marrow, followed by maintenance of response with post-remission chemotherapy.

Chemotherapy alone may not be sufficient to completely eradicate leukaemia cells. In such cases, stem cell transplantation (SCT)—also known as bone marrow transplantation—may need to be considered.

SCT is a highly specialised procedure that involves replacing the patient's abnormal bone marrow cells with normal stem cells. There are two types of SCTs:

• Autologous SCT, where stem cells are taken from the same patient and reinfused to replace stem cells destroyed from chemotherapy or radiation therapy. This type of SCT is not commonly done for patients with Acute Leukaemia.
• Allogeneic SCT, where stem cells come from a suitable matched donor. This is commonly done for patients with high-risk Acute Leukaemia.

As SCT involves an intensive conditioning regimen with risks and side effects, patients will need to be assessed based on age, general health, and availability of suitable donors to determine eligibility for SCT.

Although Acute Leukaemia is a challenging disease to manage due to its rapid progression, emerging treatment advances are paving new roads for improved patient outcomes in the management of the disease.

One of the latest developments in blood cancer treatment is Chimeric Antigen Receptor (CAR) T-cell Therapy, a form of immunotherapy that harnesses the body's immune system to target cancer cells. The treatment involves genetically engineering a patient's T-cells in a laboratory setting to produce CAR T-cells which, when reinfused into the patient, have the ability to recognise specific targets on cancer cells and destroy them using the patient's own immune response.

CAR T-cell Therapy has shown promising outcomes for the treatment of relapsed or refractory Leukaemia, with an overall success rate of 70-80% in achieving remission². The treatment is currently approved for use in children and young adult patients aged 2-25, with B-cell Acute Lymphoblastic Leukaemia (ALL) that is resistant, and where a relapse has occurred subsequently or post-transplant.

Treating other subtypes of Leukaemia

In the past, chemotherapy was the mainstay of treatment for chronic Leukaemia and other subtypes of Leukaemia. However, thanks to recent medical advances, the treatment paradigm for chronic and other Leukaemia has shifted from chemotherapy to targeted therapy alone.

Targeted therapy is a type of precision medicine that targets specific genes and proteins that control how cancer cells grow, divide, and spread. Compared to chemotherapy, targeted therapy is directed to a specific cancer target and therefore has reduced effects on surrounding healthy cells. What this means is that patients have shorter recovery times and can go about their normal lives without worrying about side effects or complications often associated with chemotherapy.

More revolutionary breakthroughs ahead

Patients with Leukaemia can be treated to great degrees of success today, thanks to groundbreaking medical and technological developments in the field of haematology over the last decade.

The advent of CAR T-cell Therapy, for example, has brought about significant survival advantages that show the potential of novel treatment advances to carve new frontiers in the treatment of Leukaemia as well as other blood cancers. In the near future, we expect more revolutionary breakthroughs ahead in the field that will bring new hope for survival for patients with various blood diseases.