Treatment of Pediatric Acute Promyelocytic Leukemia with Retinoic Acid and Arsenic Trioxide along with Chemotherapy

• Published in: Indian journal of pediatrics 2024-06, Vol.91 (6), p.564-570
• Main Authors: Srinivasan, Shyam, Dhamne, Chetan, Moulik, Nirmalya Roy, Chichra, Akanksha, Tembhare, Prashant, Patkar, Nikhil, Subramanian, P. G., Shetty, Dhanlaxmi, Narula, Gaurav, Banavali, Shripad
• Format: Article
• Language: English
• Subjects: Adolescent; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Arsenic Trioxide - therapeutic use; Child; Child, Preschool; Female; Gynecology; Humans; Infant; Leukemia, Promyelocytic, Acute - drug therapy; Leukemia, Promyelocytic, Acute - mortality; Male; Medicine; Medicine & Public Health; Original Article; Pediatrics; Retrospective Studies; Tretinoin - therapeutic use
• ISSN: 0019-5456; 0973-7693
• DOI: 10.1007/s12098-023-04689-4

Objectives Outcomes of childhood acute promyelocytic leukemia (APL) have exceeded 90% in the era of differentiating agents. In resource-limited settings, early mortality secondary to coagulopathy remains a significant challenge. Differentiation syndrome is a unique complication of APL therapy that requires a high degree of suspicion for timely initiation of therapy. Methods A retrospective study of children ≤15 y of age with APL diagnosed between January-2013 and June-2019 treated at a tertiary cancer centre was conducted. Patients with a total leukocyte count ≥10,000/µL were risk stratified as high-risk. Treatment included differentiating agents, all-trans retinoic acid and arsenic trioxide along with chemotherapy. Baseline demographics, clinical complications and outcomes were analysed. Results Out of 90 patients treated, 48 (53%) had high-risk APL and 25 (28%) presented with significant bleeding manifestations. Response to therapy was excellent with 96% of evaluable patients achieving molecular remission by the end of consolidation phase. Differentiation syndrome occurred in 23 (25%) patients of which two expired. Early mortality rate was 5.5% and was due to severe hemorrhage most often at the time of presentation. The 3-y overall survival of the entire cohort was 91% (95% CI: 85–97%). Two of 4 patients with relapse of disease could be salvaged with only differentiating agents followed by autologous transplantation. Conclusions Long-term outcomes of Indian children with APL are excellent. Timely management of coagulopathy and prompt initiation of differentiating agents along with appropriate cytoreductive measures is critical. Efforts to build academic-community partnerships to ensure timely diagnosis and emergency care in order to reduce early mortality are needed.