Venetoclax–azacitidine as a bridge to transplant in pediatric relapsed/refractory acute myeloid leukemia: A real-world experience

Abstract

Background

Survival outcomes in pediatric acute myeloid leukemia (AML) have improved significantly; however, prognosis for relapsed or refractory (R/R) disease remains dismal. This study evaluates real-world outcomes of Venetoclax-Azacytidine (Ven–Aza) as a bridge to transplant in children with R/R AML.

Methods

We retrospectively reviewed patients aged 1–18 years with R/R AML treated with Ven–Aza at a single centre (January 2022–December 2025). Treatment consisted of Aza (75 mg/m², days 1–7) and Ven with a 3-day ramp-up to body surface area–adjusted adult exposure equivalent dosing for 14 days. Responses, adverse events and survival outcomes were analysed.

Results

Fourteen patients received Ven–Aza. Median number of Ven-Aza cycles administered were 2 (Range:1-4). Best responses achieved were CR in 6 (42.8%), CRi in 2 (14.2%), PR in 1 (7.1%) and NR in 5 (35.7%), giving a composite CR/CRi of 8/14 (57.1%) and ORR of 9/14 (64.3%). MRD negativity occurred in 6 of 8 responders. Patients harbouring RUNX1 mutations showed favourable responses (CR/CRi in 4/6). Meanwhile, patients with FLT3-ITD (n = 5), TP53 (n = 1) or KRAS/NRAS (n = 2) alterations demonstrated lower response rates and a higher likelihood of disease progression. All 8 patients with CR/CRi underwent allogenic HSCT at a median of 2.5 months. Hematologic toxicities were frequent (grade ≥3 in 11); infectious complications occurred in 5 and TLS in 2 patients. Median follow-up was 10 months; 2- years OS was 28.6% (95th CI: 0.08-0.52) for whole cohort and 57.1% (95th centile: 0.17-0.83) for the patients undergoing HSCT.

Conclusion

Ven-aza demonstrated encouraging remission rates and acceptable toxicity in pediatric R/R AML, effectively serving as a bridge to HSCT.