Acute Myeloid Leukemia (AML)

Acute Myeloid Leukemia (AML) is a disorder of the process that normally produces neutrophils, a type of white blood cell. These abnormal cells rapidly fill up the bone marrow space, suppressing the normal cells. AML may sometimes be called Acute Myelogenous Leukemia, Acute Myelocytic Leukemia, and or Acute Nonlymphocytic Leukemia. Unlike chronic leukemia, acute leukemia develops quickly and generally needs immediate treatment. Acute Myeloid Leukemia is the most common type of acute leukemia which affects adults and chances of getting Acute Myeloid Leukemia increases with age.

Acute Myeloid Leukemia is caused by damage to the DNA of developing cells in bone marrow. Though exact cause is not known, several risk factors have been identified:

• Exposure to the chemical benzene
• Being male
• Smoking, especially after age of 60
• Treatment with chemotherapy or radiation therapy in the past
• Treatment for childhood acute lymphoblastic leukemia (ALL) in the past
• Being exposed to radiation from an atomic bomb
• History of a blood disorder such as myelodysplastic syndrome
• Weakened immune system due to an organ transplant
• Certain genetic disorders, including Down's syndrome and Fanconi's anaemia

The symptoms are usually similar to ALL. In certain types of AML, like Acute Monoblastic Leukemia, or Acute Myelomonocytic Leukemia, one can have symptoms of gum swelling or skin nodules.

• Fever; Fatigue; Weight loss or loss of appetite; Shortness of breath; Anaemia; Easy bruising; Severe Bleeding; Petechiae (flat, pin-head sized spots under the skin caused by bleeding); Bone and joint pain; Persistent or frequent infections; Abnormal swelling of gums around teeth

Complete Blood Count

The characteristic finding of AML is high white blood cell count with low haemoglobin and platelet count.

Peripheral Blood Smear

Presumptive diagnosis of AML can be made via examination of the peripheral blood smear when there are more than 20% blasts.

Bone Marrow Examination

This is necessary for confirmation of the diagnosis. There must be more than 20% of abnormal cells (blasts) in the marrow for it to be called Acute Myeloid Leukemia. However, in certain cases of Acute Myeloid Leukemia, presence of the characteristic abnormality in chromosome is enough to call it Acute Myeloid Leukemia even with fewer than 20% blasts in the marrow.

Flow Cytometry

AML has seven subtypes (AML-M1 ---- AML-M7). There are further subtypes in the individual categories which are confirmed via flow cytometry.

Cytogenetics

This is testing for abnormalities in the chromosomes. Certain genes are brought next to each other by a process called 'translocation' leading to uninterrupted growth and proliferation of white blood cell precursors in the bone marrow. Missing pair of a chromosome in positions 5, 7, 8 is also a feature of AML. This is called Monosomy. Certain changes in sequence of the genes called mutations are also seen which have an impact on outcome of treatment.

Classification

Unlike cancers of solid organs, ALL and other blood cancers are not staged by the extent of involvement of different organs. They are classified into: Standard-Risk or Good-Risk, Intermediate-Risk and High-Risk. This is predominantly based on the abnormality of chromosomes or genes.

Minimal Residual Disease (MRD)

Minimal Residual Disease (MRD) means patient still has a minimum disease and has not fully recovered. Response to treatment is conventionally checked with a bone marrow morphology which establishes COMPLETE REMISSION (CR). However, CR means that the number of leukemia cells in the body are less than 10⁹ or 1000 million cells. At this level, they cannot be seen under the microscope.

MRD is the detection of cells below 1%, which can range from 1 in 1000 to 1 in a million cells. This enables us to check for response to treatment with a much higher sensitivity than possible under the microscope.

Chemotherapy

Chemotherapy for AML is divided in two phases, INDUCTION and CONSOLIDATION. About 60-70% of patients achieve a complete remission. The chances of a sustained remission or cure are as follows:

• Good Risk: 50-70%
• Intermediate Risk: 30%
• High Risk: Less than 10%

What is different about treatment of APML or AML-M3?

This is a unique condition which responds to high doses of a form of Vitamin A called ALL-TRANS RETINOIC ACID (ATRA) and ARSENIC TRIOXIDE (ATO). This condition carries a 90% cure rate.

How is AML in Children Different from that in Adults?

• AML is less common in children; particularly APML
• Results of Chemotherapy are 10% better in children.
• Children less commonly have BAD chromosomes.

When is BMT needed for AML?

Chemotherapy is curative in only one-third of patients with AML. All patients with AML apart from the ones with good risk genetics or APML should undergo BMT. BMT is best done when the disease is in first CR. Very few patients who RELAPSE or do not respond to treatment are cured.

Conditioning

High to Moderate dose of chemotherapy is generally used in conditioning for BMT.

Who can be a donor?

Although we prefer a matched family donor, a Half matched (Haploidentical) family donor or an unrelated donor can also be used. However, a HAPLOIDENTICAL DONOR who has Natural Killer Cell mismatch with the patient provides the best cure for AML via Graft versus Leukemia (GVL) effect.

Results of BMT in AML

• BMT reduces the risk of relapse i.e., recurrence of disease by 80% compared to chemotherapy
• If the patient is MRD negative before BMT, the risk of relapse is low
• BMT is the only cure for patients, who relapse after chemotherapy