Venetoclax Bridges Children With Relapsed Leukemia to Transplant

VENETOCLAX-based therapy could help children with relapsed or refractory acute leukaemia achieve sufficient disease control to proceed to haematopoietic stem cell transplantation (HSCT), according to new real-world research.

In a retrospective study of 21 children, 75% of evaluable patients responded to their first venetoclax-based treatment, while 86% of those achieving complete remission or complete remission with incomplete marrow recovery became measurable residual disease (MRD)-negative.

Overcoming Resistance Before Transplantation

Relapsed or refractory paediatric acute leukaemia remains difficult to treat, particularly when conventional salvage chemotherapy fails to control disease sufficiently for transplantation.

Five-year overall survival following first relapse is approximately 48.9% for acute lymphoblastic leukaemia (ALL) and 35–42% for acute myeloid leukaemia (AML). Achieving undetectable MRD before HSCT is also associated with better outcomes.

Researchers therefore examined the use of venetoclax, a BH3-mimetic targeting BCL-2, as a bridge to HSCT.

The single-centre study included 21 children younger than 18 years treated between March 2020 and December 2025. Together, they received 26 episodes of venetoclax-based therapy.

Median age was 13 years, and patients had received a median of two previous lines of therapy. Ten had AML, six ALL, four myeloid neoplasms following cytotoxic therapy, and one mixed-phenotype acute leukaemia. Two-thirds had unfavourable cytogenetics.

Three-Quarters Responded to Initial Treatment

Among 20 evaluable patients, the overall response rate after initial venetoclax-based therapy was 75% (15/20).

Thirteen achieved complete remission, one complete remission with incomplete marrow recovery, and one a partial response.

Among the 14 patients achieving complete remission or complete remission with incomplete marrow recovery, 12 (86%) became MRD-negative. Median time to best response was 32 days.

Venetoclax-based therapy enabled 14 of 21 patients (67%) to proceed immediately to HSCT. Another patient achieved MRD-negative complete remission and elected to stop treatment and enter surveillance rather than undergo transplantation.

Median time from starting venetoclax to HSCT or CAR-T therapy was 2.4 months.

Re-Treatment Produces Responses

Five children subsequently received another venetoclax-based regimen after previous exposure.

All five responded to re-treatment, giving an overall response rate of 100%, while four of the five achieved MRD negativity. Three achieved complete remission and two complete remission with incomplete marrow recovery.

The researchers noted that all five had responded to venetoclax previously and received a different chemotherapy backbone when re-treated, making careful patient selection important when interpreting these findings.

At a median follow-up of 32.3 months after initial treatment, 13 patients (62%) remained alive. Estimated 2-year overall survival was 74.9% (95% CI: 49.6–88.8).

Toxicity and Study Limitations

The most common grade ≥3 toxicities were cytopenia, affecting 21 treatment episodes; febrile neutropenia, affecting 18; sepsis or infection, affecting 11; and diarrhoea or colitis, affecting 10.

One episode of tumour lysis syndrome occurred, while only one treatment episode required an overnight intensive care admission. Because venetoclax was administered alongside other therapies, causality for adverse events could not be definitively attributed to the drug.

The researchers cautioned that the cohort was small, heterogeneous and restricted to transplant-fit patients, potentially introducing selection bias. The retrospective study also lacked a comparator group and pharmacokinetic analysis.

Prospective studies are therefore needed to determine which children are most likely to benefit and establish optimal venetoclax-based combinations.

Reference

Colman KS et al. Venetoclax-Based Therapy as a Bridge to Hematopoietic Stem Cell Transplantation in Relapsed or Refractory Pediatric Acute Leukemia. 2026. doi:10.1002/1545-5017.70715.