How I Treat Newly Diagnosed Acute Promyelocytic Leukemia

Abstract

Acute promyelocytic leukemia (APL) represents a medical emergency with a high rate of early mortality. As a consequence, as soon as the diagnosis is suspected based upon cytologic criteria, it is necessary to start all- trans retinoic acid (ATRA) treatment without delay. For patients with newly diagnosed APL, induction therapy with ATRA plus anthracycline based chemotherapy is recommended. At present the combination of arsenic trioxide plus ATRA should be considered for patients who are not candidates for anthracycline-based therapy. For pediatric and adult patients with APL aged < 60 years who achieve a CR with induction, I recommend 3 intensive courses of consolidation chemotherapy associated to ATRA, targeted on the basis of the risk group at diagnosis. In patients treated with a very intensive consolidation chemotherapy maintenance treatment can be omitted. However If a maintenance treatment has to be adopted I suggest the use of intermittent ATRA for 15 days every 3 months for a period of 2 years, rather than ATRA associated to chemotherapy. Moreover, taking into account the medical literature, a reduced dosage of ATRA ( 25 mg/m2) in pediatric patients and a consolidation chemotherapy of reduced intensity in elderly patients is recommended. Furthermore, in order to maximize survival, careful attention should be reserved to the coagulopathy and to the appearance of the differentiation syndrome. Finally, PCR for the PML/RARA fusion gene on a bone marrow specimen every three months for two years, and then every six months for additional three years are needed during the follow-up.

Acute Promyelocytic Leukemia (Apl): Comparison Between Children and Adults

“… 53 Relatively high-dose anthracyclines (450–750 mg/m 2 ) used in modern chemotherapy plus ATRA regimens have proven successful to achieve high cure rates in adults and children with APL, although the high cumulative anthracycline dose was potentially associated with high risk of late cardiotoxicity. 4 , 6 , 7 , 44 Although no severe acute cardiotoxicity was observed in our first GIMEMA-AIEOP study, longer follow-up is needed to define the late cardiotoxicity of anthracycline regimens. Late subclinical cardiotoxicity was observed in 52% of the adult survivors of APL treated on the GIMEMA AIDA-0493 and-2000 protocols.…”

“…As suggested by Van Dalen et al, the risk of developing clinical heart failure is dose-dependent, increasing from 0% for 150 mg/m 2 of cumulative anthracycline dose, up to 14.3% for doses of 600 mg/m 2 53. Relatively high-dose anthracyclines (450–750 mg/m 2 ) used in modern chemotherapy plus ATRA regimens have proven successful to achieve high cure rates in adults and children with APL, although the high cumulative anthracycline dose was potentially associated with high risk of late cardiotoxicity 4,6,7,44. Although no severe acute cardiotoxicity was observed in our first GIMEMA-AIEOP study, longer follow-up is needed to define the late cardiotoxicity of anthracycline regimens.…”

Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives

“…Anthracycline-related cardiotoxicity is also a concern106,107 as research has shown that patients treated on AIDA-based protocols developed subclinical but detectable diastolic dysfunction and regional wall motion abnormalities 106. Recognized common acute side effects associated with ATRA therapy include fever, rash, headache and pseudotumor cerebri; the latter occurs more commonly in adolescents/children and may prompt dose reduction or cessation of ATRA in severe cases 108. Long-term toxicity secondary to ATRA therapy has not been seen but requires ongoing review.…”

“… 106 Recognized common acute side effects associated with ATRA therapy include fever, rash, headache and pseudotumor cerebri; the latter occurs more commonly in adolescents/children and may prompt dose reduction or cessation of ATRA in severe cases. 108 Long-term toxicity secondary to ATRA therapy has not been seen but requires ongoing review.…”