Successful Treatment of Acute Promyelocytic Leukemia (APL) In a Patient with Severe Cardiac Disease

The standard and often curative regimen for APL includes cardiotoxic daunorubicin and All-Trans Retinoic Acid (ATRA). Arsenic trioxide (ATO), like ATRA, induces leukemic blast differentiation and is active in APL.

A 58 year old African American man had a metallic aortic valve replacement 6 years prior to presentation, for which he was on warfarin, coronary artery disease, a left ventricular ejection fraction of 20%, and an implanted cardioverter-defibrillator. He presented with dyspnea, fever, scattered rales and ecchymoses and petichiae. His white blood count was 38,000/mcl, with 51% promyelocytes and 8% neutrophiles, Hb 9.7 g/dl, and platelets of 12,000/mcl. Fibrinogen was 172 mg/dl, aPTT 28 seconds, and international normalized ratio 2.3; lactate dehydrogenase was 1593 U/dl. The bone marrow (BM) was replaced by promyelocytes, karytotype revealed t (15;17) (q22;q12), and fluorescent in situ hybridization (FISH) showed the promyelocytic leukemia – retinoic acid receptor fusion product (PML-RARA). The diagnosis was high risk APL. Warfarin was suspended, and treatment was initiated with ATRA 45 mg/M2. On day 7, he developed shortness of breath; cough and chest radiograph illustrated marked interstitial edema as well as bilateral pleural effusion. These features of the differentiation syndrome resolved rapidly after transfer to the Medical Intensive Care Unit and dexamethasone initiation. On day 10, daily ATO at 0.15 mg/kg IV was initiated. His QTC interval ranged from 430–600 ms, showed interactions with 5-HT inhibitors and antifungal drugs, and stabilized after discontinuation of these drugs. By day 23, his white blood cell counts had normalized, and BM aspiration showed normal morphology. ATO was discontinued, platelet count rose to 50,000/mcl by day 28, when warfarin was resumed. Post-induction the patient received 4 cycles of ATO 5 days per week for 4 weeks, each followed by 4 weeks off treatment and ATRA 45 mg/m2 daily for 2 weeks every 4 weeks for a total of 7 cycles. Cytogenic remission was confirmed by FISH analysis of BM on days 23 and 113, and subsequently by quantitative RT-polymerase chain reaction on peripheral blood specimens for one year. By these criteria he remains in complete remission one year after presentation.

With careful cardiac monitoring, ATRA-ATO induced a durable complete remission of APL in a patient with several major cardiac contra-indications to anthracyclines. Despite the patient's metallic aortic valve, he tolerated suspension of anti-coagulant therapy well.

No relevant conflicts of interest to declare.