Supportive Care

The prevention of abnormal bleeding is critical.

Key aspects of Supportive Care are fully described in Supportive Care for AML.

There is some evidence that azoles are not required for fungal prophylaxis in APML as the period of neutropenia is short.

Tretinoin (ATRA) may be complicated by a specific set of symptoms referred to as differentiation (ATRA) syndrome.

Arsenic Trioxide may cause QT prolongation on ECG, hepatotoxicity and/or neurological toxicity.

Differentiation (ATRA) syndrome

Diagnosis of the differentiation (ATRA) syndrome should be suspected clinically in the presence of one of the following symptoms and signs:

dyspnoea

unexplained fever

weight gain

peripheral oedema

unexplained hypotension

acute renal failure or congestive heart failure (particularly by a chest radiograph demonstrating pulmonary infiltrates)

pleuropericardial effusion

We recommend checking O₂ saturations initially at least 4-hourly until white count has dropped, then 8-hourly while an inpatient, or more often if there are any respiratory symptoms. The following account of the ATRA Syndrome is taken from Sanz, M. A., M. S. Tallman, et al. (2005). Tricks of the trade for the appropriate management of newly diagnosed acute promyelocytic leukemia. Some minor modifications have been made.

In addition to the aforementioned supportive measures aimed at counteracting the coagulopathy, physicians caring for patients with APML should be aware of early symptoms or signs suggestive of differentiation (ATRA) syndrome.

At the earliest manifestation of suspected differentiation (ATRA) syndrome, e.g. unexplained respiratory distress), and before the development of a fulminant syndrome, the following measures should be undertaken immediately:

Temporary discontinuation of tretinoin (ATRA).
Prompt initiation of dexamethasome 10 mg IV 12 hourly until disappearance of signs and symptoms, and for a minimum of 3 days.
Frusemide when clinically indicated.

While early therapy with dexamethasone currently represents the standard approach to treat patients who develop differentiation syndrome, there is currently no controlled trial evidence that prophylactic corticosteroid is advantageous to reduce rates of morbidity and mortality associated with this syndrome. Nevertheless, in uncontrolled studies, a very low mortality or morbidity rate was reported as a result of differentiation syndrome by administering corticosteroids prophylactically in patients with white blood cell (WBC) count >5 x 10⁹/L. (We recommend you follow this advice. If the WBC rises by more than 4 x 10⁹/L from baseline during the first 2 to 3 days of treatment, give dexamethasone in a dose of 10 mg IV or orally BD.)

Besides these specific measures to reduce the rates of differentiation syndrome and haemorrhage-associated morbidity and mortality, the policy for other supportive measures, including use of hematopoietic growth factors, does not differ from that commonly used for patients with other subtypes of AML.

Other Side Effects of Tretinoin (ATRA)

Pseudotumour Cerebri – severe headaches with nausea, vomiting, and visual disorders. This generally develops in patients younger than 20 years. Temporarily discontinue tretinoin and administer opiates.

Hepatotoxicity -> 5 X ULN increase in liver enzymes. Discontinue tretinoin. If hepatotoxicity persists, discontinue arsenic (ATO) in the tretinoin/arsenic arm. The idarubicin dose in the AIDA arm should continue.

Lip and skin dryness may be alleviated by cream and eye drops. Nasal drops or vaseline may be required for frequent epistaxis due to breaks in the nasal mucosa.

Nausea and vomiting may require antiemetic therapy.

Transient bone and joint pain will require analgesia. If pain is severe and narcotic analgesia is required, consider reduction of tretinoin (ATRA).

Triglyceride levels may increase.

Hyperhistaminaemia with marked basophilia may occur, resulting in shock without Retinoic Acid Syndrome. If suspected, check histamine levels. Chemotherapy should be commenced after control with antihistamines.

Tretinoin (ATRA) may be teratogenic. This means patients and partners of patients on tretinoin (ATRA) need to receive appropriate information about contraception.


About this Canterbury DHB document (4484):
Document Owner:	Blake Hsu (see Who's Who)
Last Reviewed:	October 2018
Next Review:	October 2020
Keywords:
Note: Only the electronic version is controlled. Once printed, this is no longer a controlled document. Disclaimer The Haematology Department Protocols and Guidelines (the Red Book) are intended as a guide for registered health professionals to communicate guidelines and share best practices with supporting health professionals within New Zealand district health boards. They are not intended to be provided to or used as a reference for patients or non-registered health professionals. All health professionals must exercise their own clinical judgement and use pertinent clinical data when treating patients. The authors and editors of this publication have checked with sources believed to be reliable in their effort to provide information that is complete and in accord with the standards accepted at the time of publication. However, in view of the possibility of human error or changes in medical science, neither the authors, editors, publisher, nor any other party who has been involved in preparing or publishing this work warrants that the information contained in it is accurate or complete in every respect. They therefore have no liability (whether in tort (including negligence) or otherwise) for any loss or damage arising out of any reliance on this information. This publication has been compiled by the staff and contractors of Canterbury District Health Board (CDHB) and as such CDHB has copyright for this book. Amendments must be authorised in accordance with the documented process. No release of part of, or all of, this publication to any other party or organisation is permissible without the prior approval of the designated document owner.
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Topic Code: 4484