# Clinical and Molecular Profiles and Treatment Outcomes in Patients With Acute Promyelocytic Leukaemia: A Single-Centre Experience

## TL;DR

This study analyzes clinical and molecular features of acute promyelocytic leukemia patients and finds that ATRA and ATO treatment leads to high remission and low relapse rates.

## Contribution

The study provides insights into treatment outcomes and molecular profiles of APL patients in a single-center setting.

## Key findings

- Most APL patients presented with fever and bleeding as primary symptoms.
- ATRA and ATO-based treatment achieved high remission rates with low relapse.
- The PML-RARα bcr1 transcript was the most common subtype observed.

## Abstract

Introduction: Acute promyelocytic leukaemia (APL) is one of the most treatable blood cancers with a high cure rate. The reciprocal translocation t (15; 17) results in the formation of the promyelocytic leukaemia-retinoic acid receptor alpha (PML-RARα) gene and its fusion protein, which are hallmarks of this disease. Patients often present with bleeding diathesis and may experience a fulminant early course. Outcomes with all-trans retinoic acid-based regimens are very favourable. In this study, we share our experience with APL at our centre.

Objective: The study aimed to study clinical and molecular profiles and treatment outcomes in patients with APL.

Materials and methods: We collected data on all patients diagnosed with and treated for APL at our centre between June 2019 and December 2024. APL was diagnosed based on the PML-RARα mutation and identified by reverse transcriptase real-time polymerase chain reaction or fluorescent in situ hybridisation, along with bone marrow aspiration morphology and immunophenotyping by flow cytometry. Baseline data, including demographic, clinical and molecular characteristics, therapy details, complications, and outcomes, were recorded. Baseline risk stratification was performed using the modified Sanz criteria.

Results: A total of 40 patients with APL were evaluated. The male-to-female ratio was 3:1. Patients' ages ranged from 4 to 79 years, with a median age of 37 years. The most common presenting feature was fever (55%), followed by bleeding (35%), dyspnoea (15%), generalised weakness (7.5%), and altered sensorium (2.5%). According to the modified Sanz criteria, 23 (57.5%) patients were classified as low risk, while 17 (42.5%) were classified as high risk. The PML-RARα fusion gene was detected in all patients, with the distribution of breakpoint cluster region 1 (bcr1), bcr2, and bcr3 transcripts being 20 (50%), 1 (2.5%), and 19 (47.5%), respectively. Coagulation parameters did not significantly differ between low- and high-risk groups. Twenty-nine (72.5%) patients received all-trans retinoic acid (ATRA) and arsenic trioxide (ATO)-based induction chemotherapy, while 11 (27.5%) received ATRA, ATO, and daunorubicin-based induction chemotherapy. Differentiation syndrome occurred more frequently in the high-risk group than in the low-risk group (p=0.001). The most common complication during induction chemotherapy was febrile neutropenia (97.5%). The transfusion requirement during induction was higher for bcr1 and bcr3 transcripts, but this did not reach statistical significance (p>0.05). Morphological remission was achieved in 92.5% of patients. Induction mortality was 7.5%. All patients except one received ATRA and ATO-based consolidation. No mortality was observed during consolidation. At the end of consolidation, 92.5% of patients were in morphological and molecular remission. A total of 16 (40%) patients received maintenance treatment with ATRA, 6-mercaptopurine, and methotrexate. Relapse was observed in 2 (5%) patients. At a median follow-up of 30 months, the event-free survival of the entire cohort was 87.5%.

Conclusion: Most patients with APL presented with fever and bleeding. The bcr1 transcript of PML-RARα was the most commonly observed. ATRA and ATO-based treatment was associated with high remission rates, manageable toxicity, and a low relapse rate.