SP15 | ATRA-ATO WITHOUT CHEMOTHERAPY IN TWO SELECTED PATIENTS WITH HIGH-RISK ACUTE PROMYELOCYTIC LEUKEMIA

Acute promyelocytic leukemia (APL) is cured with the combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) without chemotherapy, especially for standard APL (with baseline white blood count (WBC)<10x109/L). However, the prognosis of high-risk APL (WBC>10x109/L) even with the improved results of the APOLLO trial, remains inferior than to standard-risk APL. Aim: To evaluate efficacy and safety in two very selected patients with APL patients not candidate to receive chemotherapy as induction. Methods: We retrospectively analyzed patient chats of 2 high-risk APL patients diagnosed in 2024. APL was treated as the standard arm of the GIMEMA APL0406 protocol. Results: In December 2024, a 26-year-old male with a history of severe intellectual disability and allergy, was admitted to the ER for fever and syncope. He had Hgb 3.2 g/dL, GB 19.50x109/L, N 6.28 x109/L, PLTs 39.000, PCR 21 with 75% of myeloid blasts. Bone marrow aspiration revealed 87% of blasts CD12/CD33/CD117/CD117+ CD34-. PML::RARα was positive, so APL diagnosis was established. He started immediately cytoreduction with hydroxyurea and ATRA, and the day after, ATO 0.15 mg/kg for 28 day. Treatment was well tolerated. He achieved CR after induction and started the 2nd ATRA/ATO consolidation. The second patient was a 29-year-old female with grade 3 obesity. She had fever, menstrual bleeding, and sore-throat. Hb 10 g/dL, WBC 10.3 x109/L, N 2.3 x109/L, M 6.8 x109/L, Plts 32.000. Bone marrow showed 73% of blasts CD13/CD33/ CD117/CD123+; PML::RARα, isoform BCR1 was positive, consistent with APL. She started ATRA/ATO reduced at 12 mg with hydroxyurea. She developed leukocytosis and skin infection treated with daptomycin. A CR was reached after induction and she will start the 2nd ATRA/ATO consolidation. Conclusions: This case-series confirms that ATRA-ATO is feasible and effective in selected high-risk APL, who are at higher risks of complications from anthracyclines. Our 2 patients, albeit young, had significant risks of complications from idarubicin. The differentiation between standard and high-risk APL lacks a biological basis (WBC counts are a continuum), was developed before ATRA-ATO. As demonstrated by the APOLLO trial (still there are 2 doses of idarubicin), treating high-risk APL with less chemotherapy is beneficial. Conversely, ATRA-ATO in high-risk APL could be associated with increased risks of hyperleukocytosis requiring cytoreduction. Further prospective studies are needed.