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Acute Myeloid Leukaemia

  • Overview Symptoms Causes Diagnosis Treatment
Overview

Leukaemia are cancers that start in cells that would normally develop into different types of blood cells. Most often, leukaemia starts in early forms of white blood cells, but some leukaemia start in other blood cell types. There are several types of leukaemia, which are divided mainly on whether the leukaemia is acute (fast growing) or chronic (slower growing), and whether it starts in myeloid cells or lymphoid cells.

Acute myeloid leukaemia (AML) has many other names, including acute myelocytic leukaemia, acute myelogenous leukaemia, acute granulocytic leukaemia, and acute non-lymphocytic leukaemia. AML starts in the bone marrow (the soft inner part of certain bones, where new blood cells are made), but most often it quickly moves into the blood, as well. It can sometimes spread to other parts of the body including the lymph nodes, liver, spleen, central nervous system (brain and spinal cord), and testicles.

Most often, AML develops from cells that would turn into white blood cells (other than lymphocytes), but sometimes AML develops in other types of blood-forming cells giving rise to different subtypes of AML, as classified by WHO and the FAB systems. The sub-typing depends upon the morphology of cancer cells. Each of these types has a different natural history, presentation and prognosis.

Symptoms

Presently, no screening tests have been shown to be helpful in finding acute myeloid leukaemia (AML) early. AML often develops and causes symptoms to surface fairly quickly. Therefore, the best way to find AML early is to report any possible symptoms of AML right away.

Certain groups of people are known to be at high risk of AML because they have certain blood disorders, such as a myelodysplastic syndrome or inherited disorders such as Down syndrome, or because they were treated with certain chemotherapy drugs or radiation.

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
  • 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 radiation
  • Exposure to 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

Chemotherapy is the main treatment for most people with acute myeloid leukaemia (AML). Chemo is often not recommended for patients in poor health, but advanced age by itself is not a barrier to getting chemo. It is usually divided into two phases

  • Induction Soon after diagnosis an intensive course of treatment begins to bring about, or induce, a remission. The goal is to clear the blood of leukaemia cells (blasts) and to reduce the number of blasts in the bone marrow to normal.
  • Consolidation After induction therapy finishes and remission is achieved; more treatment is required to help destroy any leftover disease in your body. This helps prevent a relapse and/or a spread to the central nervous system. consolidation therapy chosen will depend on the estimated risk of relapse.
  • A third, maintenance phase (or post-consolidation), involves giving a low dose of chemo for months or years after consolidation is finished. This is often used to ?treat acute promyelocytic leukemia (APL), but it is rarely used for other types of AML.

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.

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

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.

Favourable outcome 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 favourable outcome rate for all patients with AML (including the elderly and those unable to tolerate aggressive therapies) is likely lower. Favourable outcome rates for promyelocytic leukaemia can be as high as 80% - 90%.