Treatment Outcomes in Acute Promyelocytic Leukemia Patients Using a Uniform ATRA + ATO Consolidation Therapy Regimen across All Risk Groups: A Single Centre Study from India

INTRODUCTION Acute Promyelocytic Leukemia (APL) is a particularly aggressive subtype of acute myeloid leukemia associated with high risk of early mortality due to coagulopathy & bleeding. The current standard induction therapy for APL comprises of all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO), with or without anthracyclines. However, the consolidation regimens recommended for APL are highly variable according to risk group & cardiac function, and include different combinations of ATRA, ATO, anthracyclines, cytarabine, &/or gemtuzumab ozogamicin. Anthracyclines have been historically included in consolidation regimens, particularly in high-risk (HR) patients. Herein, we present the treatment outcomes with a uniform ATRA+ATO consolidation regimen in both low-risk(LR) & HR APL patients. AIMS To study the clinical outcomes in APL patients treated with uniform ATRA+ ATO consolidation regimen across all risk groups. METHODS Data of all APL patients who were treated between October 2021 & July 2024 was retrospectively analysed. Induction therapy consisted of ATRA at 45mg/m2 plus injection ATO at 0.15mg/kg daily, till documentation of morphological complete remission (CR). HR patients received 1-2 doses of Daunorubicin at 60mg/m2 dose. All the patients, irrespective of their baseline risk stratification, received uniform consolidation therapy comprising of ATRA+ATO. Injection ATO was administered at dose of 0.15 mg/kg/day by intravenous infusion, for 5 days/week for 4 weeks, every 8 weeks for a total of 4 cycles. ATRA was administered at dose of 45 mg/m2/day for 2 weeks every 4 weeks, for a total of 7 cycles. Patients below 18 years of age received ATRA at 25 mg/m2/day dose. Bone marrow PCR for PML-RARA for assessment of molecular remission was done after the 3rd cycle of consolidation. None of the patients who completed consolidation therapy received any maintenance therapy. All patients in HR group received four doses of intrathecal cytarabine in consolidation phase for CNS prophylaxis. RESULTS Total 39 patients were diagnosed with APL (LR 54%, HR 46%) and were started on induction therapy. The median age was 30 years (range 9-72) and male: female ratio was 1.2:1. The median total leukocyte count & platelet count at presentation were 3.6x109/L (range 0.29-176) and 17x109/L (range 2-48) respectively. Sixty percent of patients had disseminated intravascular coagulation (DIC) & 20% had intracranial bleed at the time of presentation. Approximately 32% patients developed differentiation syndrome during induction therapy. Nine patients (23%) died in early induction phase due to intracranial hemorrhage (80% of them had high-risk APL), & one died of severe differentiation syndrome. Morphological CR was achieved in 100% (n=29) patients who completed induction phase therapy. Molecular remission was achieved in 100% patients with the uniform ATRA+ATO consolidation strategy. Only two out of 29 patients required dose reduction of ATO during consolidation phase treatment due to myelosuppression. None of the patients developed febrile neutropenia or infection & none required any blood product transfusion in consolidation. There was no significant non-hematological toxicity in consolidation phase. All patients were followed up for at least two years after end of consolidation therapy. All the patients are alive on follow up and there has been no incidence of hematological or CNS relapse. CONCLUSION In our single-institution experience, a uniform ATRA + ATO consolidation therapy regimen in both LR & HR APL was associated with 100% molecular remission & 100% survival, while avoiding the risk of chemotherapy-induced myelosuppression & need for intensive supportive treatment in high-risk patients in our resource-limited settings.