A European LeukemiaNet (ELN) expert panel reviewed recent advances in frontline and relapse management of acute promyelocytic leukemia (APL) and provided updated guidelines for treatment in an article published in Blood. The panel addressed indications on genetic diagnosis, management of complications and treatment toxicities, molecular assessment of response, and management in special populations.

The panel recommended immediately admitting patients with suspicion of APL to the hospital, initiating all-trans retinoic acid (ATRA), and managing coagulopathy. Confirmation of APL by genetic diagnosis should follow.

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Routine monitoring of coagulation parameters at least daily until disappearance of all signs of coagulopathy was recommended. The panel further noted that transfusions should be initiated immediately and continued to maintain appropriate fibrinogen concentration, platelet count, and international normalized ratio.

Cytoreductive therapy with ATRA should be started upon suspicion of APL. High-risk patients should also receive chemotherapy, and low-risk patients may receive antileukemic agents upon genetic diagnosis of APL. Because previous studies have demonstrated the efficacy of ATRA plus arsenic trioxide (ATO), the expert panel recommended treating low-risk patients as well as patients not receiving chemotherapy with ATRA plus ATO.

After consolidation therapy, a bone marrow molecular assessment should be performed to confirm complete response (CR) with negative minimal residual disease (MRD). Routine monitoring was not recommended after induction therapy or in low-risk patients with CR with negative MRD after consolidation. MRD monitoring every 3 months for up to 3 years after consolidation was recommended for high-risk patients.

Because of the efficacy of ATRA and ATO seen in low-risk patients, the expert panel stated that maintenance therapy after consolidation was not needed. Maintenance therapy should be continued in high-risk patients receiving ATRA and chemotherapy who showed clinical benefit.

Elderly patients with good clinical conditions should receive the same treatment as younger patients, with a small dose reduction similar to the treatment of low-risk patients with APL.

Patients with evidence of molecular or hematologic relapse after consolidation should be crossed over according to the previously used treatment: patients who previously received ATRA plus ATO should receive ATRA plus chemotherapy and vice versa. Autologous hematopoietic stem cell transplant should be performed in patients who have achieved second molecular remission, have negative MRD, or are PCR negative.

Finally, the patient’s individual genetic variants of APL should inform treatment. Patients with ATRA-sensitive variants should be treated with ATRA and anthracycline chemotherapy, while those with ATRA-resistant variants might not benefit from ATRA treatment.

Disclosures: Multiple authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Reference

  1. Sanz MA, Fenaux P, Tallman MS, et al. Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet [published online February 25, 2019]. Blood. doi: 10.1182/blood-2019-01-894980