Contemporary Epidemiology of Veno-Occlusive Disease/Sinusoidal Obstructive Syndrome (VOD) in Pediatric Patients Transplanted for Acute Leukemia: Association with Antibody-Drug Conjugate Medications

Document Type

Conference Proceeding

Publication Date

2-2026

Publication Title

Transplantation and Cellular Therapy

Abstract

Introduction: Increasing and earlier use of antibody-drug conjugates (ADCs) for targeted delivery of calicheamicin has improved pediatric acute leukemia outcomes. However, ADC exposure increases VOD risk in patients undergoing subsequent hematopoietic cell transplantation (HCT) and data on incidence with contemporary dosing of ADCs is limited. Objective: Define the incidence of VOD in pediatric patients after first HCT for relapsed B-ALL and AML; evaluate its association with ADCs: Inotuzumab-ozogamicin (InO) and Gemtuzumab-ozogamicin (GO).

Methods: This retrospective multi-institutional study comprised two independent cohorts. The B-ALL cohort (ReCALL-1) included patients with relapsed B-ALL from 2018-2022. The AML cohort (REAL-AML) included patients with AML diagnosed from 2011-2024. The primary outcome was time to clinically diagnosed VOD. Secondary outcomes included severe VOD (EBMT grade 3+) and non-relapse mortality (NRM). Multivariable regression estimated adjusted hazard ratios (aHR) by ADC exposure, accounting for baseline covariates that differed by ADC exposure (Table 1, Fig 2).

Results: The B-ALL and AML analytic cohorts included 264 (37 sites) and 278 (6 sites) patients with median follow-up of 39 and 55 months after HCT, respectively (Table 1). The cumulative incidence of VOD was 17% (95% CI 13-23%) and 20% (95% CI 16-16%) in ALL and AML, at a median of day +14 (range 4-47) and +17 (range 6-37) post-HCT, respectively. The majority of cases (85%) were severe.

In B-ALL, 26% received InO, median 3 doses (range 1-10). InO associated with an increased risk of VOD (Fig 1A), severe VOD (60-day incidence 26% v 10%, Gray's p < .001 ) and NRM (3-year incidence 18% v 7%, Gray's p = 0.02). InO-exposed patients were more likely to require post-HCT intensive care with VOD (17% v 7%, p = 0.009) and overall (32% v 16%, p = 0.006). Associations persisted in multivariable models, but were attenuated, and association with NRM was no longer statistically significant (Fig 2A). The InO/VOD association varied by cumulative dose and proximity to HCT. Compared to no InO, aHRs for 1-3 and 4+ doses of InO were 1.8 (95% CI 0.8-3.8, p = 0.1) and 2.8 (95% CI 1.2-6.5, p = 0.02), respectively; and for InO exposure >60 days pre-HCT and ≤60 days of HCT were 1.2 (95% CI 0.5-3.1, p = 0.7) and 3.0 (95% CI 1.5-6.0, p = 0.002), respectively. In AML, 29% received GO, median 1 dose (range 1-3). GO associated with an increased risk of VOD (Fig 1B) and severe VOD (60-day incidence 24% v 14%, Gray's p = 0.04 ), but not NRM or intensive care. Associations were similar after multivariable adjustment (Fig 2B). No dose or timing dependency was observed. Conclusion: In this real-world, contemporary cohort of pediatric ALL/AML, HCT portends a 17-21% risk of VOD and ADCs are associated with a nearly 2-fold risk of VOD. The risk related to InO, but not GO, is dose and timing dependent. Future analyses will evaluate prophylactic strategies in high-risk groups.

Volume

32

Issue

2 Suppl

First Page

S573

Comments

Helen DeVos Children's Hospital

Tandem Meetings of ASTCT and CIBMTR, Feb 4-7, 2026, Salt Lake City, UT

Last Page

S574

DOI

10.1016/j.jtct.2025.12.862

ISSN

2666-6375

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