Canterbury DHB

Context

Treatment of non-trial patients

Patients who do not enter the AML19 APML trial will be treated with induction and consolidation as per the AIDA arm of the trial.

In This Section

Management of Relapse or Refractory Patients

Arsenic Treatment

Supportive Care

Management of Relapse or Refractory Patients

If a patient with APML relapses, reinduction with arsenic and tretinoin (ATRA) as per AML17 provides an excellent chance of achieving a molecular CR. If not in molecular remission at day 60, consider adding Idarubicin as per AIDA protocol. An autograft or allograft may now be appropriate treatments, as APML will almost certainly relapse if arsenic is not followed by further chemotherapy.

Patients who have only received arsenic and tretinoin (ATRA) should be treated with AIDA.

Arsenic Treatment

Arsenic, when given as a daily infusion, is effective in both de novo and relapsed APML, with a haematological CR of about 80%. It causes minimal haematological toxicity, though can be quite difficult to give consistently in some patients with borderline QTc intervals. Arsenic is effective against both tretinoin (ATRA) sensitive and resistant APML. Its mode of action is by the induction of apoptosis via its interaction with the PML-RARα fusion protein, which it degrades. During induction it is usually given daily for 4-6 weeks by IV infusion. In the consolidation phase, a number of different schedules have been used. It can be combined with tretinoin (ATRA) or chemotherapy. Prescription charts for Arsenic are available.

See also side effects of arsenic trioxide.

For full details of this treatment, see Mathews et al, 2006.

Administration

Arsenic trioxide comes in 10 mL vials (1 mg/mL). It should be diluted with 100-250 mL 5% glucose or 0.9% sodium chloride. It is infused over 1-2 hours but can be extended up to 4 hours if reactions occur. A CVAD is not required.

Dose

Tretinoin (ATRA)

45 mg/m²/day will be administered orally in two divided doses (rounded to the nearest 10 mg increment) starting on day 1. Tretinoin (ATRA) treatment should be continued until haematological complete remission or for a maximum of 60 days.

Arsenic Trioxide (ATO)

0.30 mg/kg IV over 2 hours daily for 5 days (days 1-5) in week 1, and thereafter 0.25 mg/kg IV over 2 hours twice a week for an additional 7 weeks.

Consolidation: Tretinoin (ATRA)

45 mg/m²/day will be administered orally in two divided doses and rounded to the nearest 10 mg increment. Treatment will be administered for 2 weeks on, followed by 2 weeks off, for a total of 7 cycles (last cycle administered in weeks 25-26).

Arsenic

0.30 mg/kg IV over 2 hours daily for 5 days, in week 1. In weeks 2-4, arsenic will be given on 2 days a week in a dose of 0.25 mg/kg. This is followed by 4 weeks with no treatment. This will be repeated for a total of 4 cycles (last cycle administered in weeks 25-28).

Supportive Care

Side Effects of Arsenic Trioxide

This drug will be discontinued in the event of cardiac arrhythmias or severe neurological toxicity.

Anti-fungal Prophylaxis

Azoles should be avoided if treating with arsenic.

Remission Criteria

These are the same as for other forms of AML. However, the distinction between normal and abnormal promyelocytes can be difficult. The PML-RARα defect can persist for some months even though the patient has entered haematological remission. The criteria for morphological complete remission is less than 5% blast cells and no hypergranular promyelocytes.

Molecular remission should be assessed after each course of chemotherapy and then on a 3-monthly basis for 2 years. Marrow samples will be collected at day 60 – following course 1 in patients requiring prolonged tretinoin (ATRA) to achieve CR. Samples will be tested by RQ-PCR for assessment of molecular remission and also sent to the Guys Lab in London by Molecular Biology. It is important to ensure this instruction and the precise details of the stage of treatment are included on the form.

About this Canterbury DHB document (32080):

Document Owner:

Ruth Spearing (see Who's Who)

Issue Date:

October 2018

Next Review:

October 2020

Keywords:

Note: Only the electronic version is controlled. Once printed, this is no longer a controlled document. Disclaimer

Topic Code: 32080