Fig. 1: Treatment schedule for newly diagnosed patients with acute promyelocytic leukemia.
ATO was sourced from Intas Pharmaceuticals Pvt. Ltd, India, ATRA was sourced from Catalent Germany Eberbach GmbH, Germany, and mitoxantrone was sourced from Neon Laboratories, India. Arsenic trioxide (ATO) was administered at a fixed dose of 10 mg daily intravenously over 3 h (0.15 mg/kg for bodyweight <45 kg). Oral all-trans retinoic acid (ATRA) was administered 45 mg/m2 daily in two doses. Mitoxantrone was given at a dose of 10 mg/m2 intravenously daily for 2 days. Induction therapy was given for at least 42 days and until achieving complete morphologic remission or a maximum of 60 days. ATRA was started on day 7 of induction for intermediate and high-risk patients or once WBC counts were less than 5 × 109/L, whichever was later. Consolidation blocks were for 28 days each. Bone marrow RT-PCR at the end of the first consolidation was done to document molecular remission. ATRA was added to the low-risk protocol after May 2019 and hence only 4 patients who received both ATRA and ATO concurrently in induction were included in the analysis. In low-risk patients, mitoxantrone was given if WBC count >20 × 109/L in 1st week of treatment, WBC count >50 × 109/L in 2nd week of treatment, differentiation syndrome not resolving with steroids or associated with leukocytosis, or at physician discretion when there was rapid WBC count doubling. Post consolidation concurrent ATO and ATRA were administered for 10 days/month × 6 months (Blue and red squares in maintenance indicate ATO and ATRA respectively), given for 10 days a month for 6 months. Prophylactic CNS directed therapy and steroids were not administered. Patients were classified as low-risk if the peripheral blood white blood cell (WBC) count <5 × 109/L and the platelet count >20 × 109/L and as high-risk if the WBC count was ≥10 × 109/L, all others were considered as intermediate risk. Green arrows: mitoxantrone ATO: arsenic trioxide ATRA: all-trans retinoic acid BM RT-PCR: Bone marrow reverse transcriptase-polymerase chain reaction for PML-RARA. −ve: negative +ve: positive.
