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Acute Myeloid Leukaemia

Overview

Adult AML is a cancer of the blood and marrow. This type of cancer can worsen rapidly, if not treated at the right time. It is the most common type of acute leukaemia in adults. AML also goes by acute myelogenous leukaemia, acute myeloblastic leukaemia, acute granulocytic leukaemia and acute nonlymphocytic leukaemia.

There are different subtypes of AML, as classified by WHO and the FAB systems. This depends upon the morphology of cancer cells or blasts. Each of these types has a different natural history, presentation and prognosis.

APML (Acute Promyelocytic Leukaemia) or AML M3 is a sub-type that is distinct from other AMLs mainly because of how it responds to all-trans retinoic acid therapy.

AML cells can build up in the bone marrow and blood, so there is less room for healthy white blood cells, red blood cells and platelets. When this happens, infection, low haemoglobin or easy bleeding may occur. The leukaemia cells can spread outside the blood, to other parts of the body, including the brain, spinal cord, skin and gums.

Symptoms

AML can show up in the form of one or more of these symptoms:

Fever
Easy bruising or bleeding
Flat pinpoint red spots under the skin caused by bleeding
Weakness or feeling tired
Shortness of breath
Weight loss or loss of appetite
Night sweats
Many of these symptoms may occur simply because of a reduction in normal blood cells. So it is important to see a doctor for a conclusive diagnosis.

Causes

Most AML cases can't be pinned down to exact causes. However, the following risk factors are usually associated with the disease:

Smoking, especially after the age of 60
Past history of chemotherapy or radiation therapy
Having had treatment for childhood Acute Lymphoblastic Leukaemia or ALL
Being exposed to atomic bomb radiation
Exposure to the chemical benzene
Having a myelodysplastic syndrome or a bone marrow failure disease
Congenital syndromes like Down’s Syndrome
Gender (more AML patients are male)

Diagnosis

AML is diagnosed by a simple peripheral smear which requires a drop of blood and examination under microscope. A bone marrow aspiration or trephine biopsy follows. The aspirate helps in identifying blasts and special stains that differentiate other forms of acute leukaemia or from ALL.

A flow cytometry assessment and cytogenetics assessment for karyotype (chromosome arrangement patterns) using peripheral or bone marrow aspirate (preferable) will identify the immunophenotype of the AML and help in ascertaining prognosis.

The patient may need a lumbar puncture to assess spread to brain, if indicated.

Treatment

For AML, other than APML or AML M3, standard chemotherapy as part of 7+3 regimen or 5+2 regimen, using daunorubicin and cytosine arabinoside are used in induction. Once the induction therapy has decreased the blasts percentage, (to less than 5%) in the marrow, the patient undergoes consolidation therapy with high dose cytosine arbinoside.

Further, in consolidation therapy, once the patient is in complete remission, allogenic transplant may be offered to patients upfront if they have poor cytogenetics, and after first relapse in standard risk patients.

AML is a difficult disease to treat as it is very aggressive, and needs continuous monitoring and follow up. The single most important prognostic factor in AML cytogenetics or the chromosomal structure of the leukaemic cell. Certain cytogenetic abnormalities are associated with very good outcomes (for example, the (15;17) translocation in APML or AML M3). About half of AML patients have 'normal' cytogenetics. They fall into an intermediate risk group. A number of other cytogenetics abnormalities are known with a poor prognosis and a high risk of relapse after treatment.

Deletion, Inversion of chromosomes.

Risk Category Abnormality 5 Year Survival Relapse rate
Good

t(8;21), t(15;17), inv(16)

70% 33%
Intermediate

Normal, +8, +21, +22, del(7q), del(9q), Abnormal 11q23, all other structural or numerical changes

48% 50%
Poor

5, -7, del(5q), Abnormal 3q, complex cytogenetics

15% 78%

 

Cure rates in clinical trials have ranged from 20 to 45%. However, it should be noted that clinical trials often include only younger patients and those able to tolerate aggressive therapies. The overall cure rate for all patients with AML (including the elderly and those unable to tolerate aggressive therapies) is likely lower. Cure rates for promyelocytic leukaemia can be as high as 80% - 90%.

What is the role of hematopoietic stem cell transplant? Allogeneic transplant is a therapy form, wherein an HLA matched donor's stem cells are removed by peripheral vein puncture, using an apheresis machine and given to the patient after conditioning therapy. It is superior to autologous transplant, where the patient's own stem cells are used.

In case of translocation of chromosome t(8, 21), (15, 17) or inversion of ch 16, the patient comes to good risk category. The 5 year survival is rated at 70%, with a 33% chance of relapse.

In poor risk patient (those with unfavourable cytogenetics) allogenic transplant confers better survival after inducing first clinical remission than otherwise.