Canterbury DHB

Acute Promyelocytic Leukaemia

This section is currently being reviewed by Dr Blake Hsu. It was last reviewed by Dr Ruth Spearing in October 2018.

Overview

• Acute Promyelocytic Leukaemia (APML) is characterised by t(15;17) with production of PML-RARα fusion gene.
• Approximately 5-10% of AML patients have APML.
• APML usually responds promptly to a combination of a differentiating agent, tretinoin (also known as all trans-retinoic acid or ATRA), and chemotherapy. Arsenic is also effective in APML.
• APML is the most curable form of AML with a CR rate of more than 90% and a 5 year overall survival of around 80%.

  We suggest everyone treating APML reads the excellent review Tricks of the trade for the appropriate management of newly diagnosed acute promyelocytic leukemia by Sanz, M. A., M. S. Tallman, et al. (2005). Some minor modifications have been made.

Clinical Features

These are essentially the same as for other forms of AML except that the haemorrhagic tendency may be very severe and can be made temporarily worse by initial therapy. This is due to a combination of thrombocytopenia and DIC/increased fibrinolysis.

Laboratory Diagnosis

• Pancytopenia is often severe and only a few leukaemic cells may be present in the blood. The hypogranular variant is more likely to have abnormal cells in the blood.
• Coagulation tests – PT, APTT, thrombin clotting time, fibrinogen, and FDPs are classically abnormal.
• The bone marrow appearances are usually characteristic with heavy granulation and multiple Auer rods in some cells. The hypogranular variant has a monocytoid appearance.

The diagnosis may be suggested by immunophenotyping (often CD34 and HLADR negative and CD9, 13, 33 positive). The diagnosis however requires the demonstration of the t(15;17) translocation by FISH or cytogenetics, and / or the demonstration of PML-RARα by DNA analysis.

AML with cup-like blasts is classically also CD34 and HLA DR neg and may cause confusion on morphology. It may also be associated with DIC and is often associated with a high white count. It is important to distinguish this form of AML from APML. See Jalal S. et al, BJH 2010 148: 182.

For a full account of the laboratory findings of APML, refer to the WHO Classification of Tumours – Pathology and Genetics of Tumours of Haemopoietic and Lymphoid Tissues, 2008, pp 112 - 114.

Prognosis and the Decision to Treat

Prognosis

APML is included in the WHO 2016 classification of “AML with recurrent cytogenetic changes”. The prognosis for APML is better than other forms of AML with a CR rate of more than 90% and overall survival of around 80% at 5 years. The main risk of serious complications is due to bleeding, which arises at presentation and during the initial 5-7 days of treatment.

The Decision to Treat

In general, treatment should be offered to all patients with APML as soon as the t(15;17) and/or the PML-RARα defect has been demonstrated or the morphology indicates these changes are almost certain to be present.

Intensive supportive treatment to prevent bleeding plus tretinoin (ATRA)—with or without chemotherapy—is indicated in virtually all patients, regardless of age. This is because of the excellent results that are usually obtained.

In Christchurch, patients with APML will be offered treatment within the AML19 trial. See section on AML19 APML and Clinical Trials page on the Intranet. Alternatively you can phone the Clinical Trials Co-ordinator (ext: 80377).

Pre-Treatment Investigations

See the Investigations section under AML.

Management

• Treatment with tretinoin (ATRA) and supportive care for coagulopathy should be started as soon as the diagnosis is suspected.
• The immediate priority is to address any haemorrhagic tendency aggressively. FFP and/or cryoprecipitate should be given to maintain the fibrinogen at a level of >1.5 g/L and to try and normalise the PT and APTT.
• At least 1 adult dose of platelets should be given 12 hourly to maintain a platelet count > 30 x10⁹/L until the fibrinogen is above 1.5 g/L without replacement treatment.

Topic Code: 4299