TOPLINE

Among children with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) treated with inotuzumab ozogamicin before hematopoietic stem cell transplant (HSCT), defibrotide prophylaxis was associated with sinusoidal obstruction syndrome (SOS) rates comparable to those seen in patients who had not received inotuzumab.

METHODOLOGY

• Children with relapsed or refractory B-ALL often need HSCT. Prior treatment with inotuzumab ozogamicin has improved remission rates and survival compared with standard chemotherapy in relapsed/refractory disease, but the drug can also increase the risk for SOS, a life-threatening complication of transplantation. Although defibrotide is widely used in the treatment of transplant-associated SOS, its role as prophylaxis is unclear.
• Researchers conducted a single-center retrospective analysis of 92 children, adolescents, and young adults with relapsed or refractory B-ALL who underwent HSCT between January 2016 and October 2024.
• Participants were divided into those who received inotuzumab ozogamicin before HSCT (n = 32; median age at HSCT, 16.1 years) and those who did not (n = 60; median age at HSCT, 11.7 years). Overall, 34 patients received defibrotide prophylaxis for SOS prevention during HSCT; 26 of those patients received inotuzumab ozogamicin and eight did not.
• Primary endpoints included the incidence of SOS during HSCT, nonrelapse mortality at day 100 post-HSCT, cumulative incidence of relapse, relapse-free survival, and overall survival. The median follow-up duration was 3 years.

TAKEAWAY

• The incidence of SOS among patients receiving inotuzumab ozogamicin plus defibrotide prophylaxis was similar to that in patients who did not receive inotuzumab ozogamicin (15% vs 12%; P = .61). By contrast, SOS occurred in 50% (three of six) of patients in the inotuzumab group compared with 12% (six of 52) in the noninotuzumab group.
• Overall, patients who received inotuzumab had low 100-day and 3-year nonrelapse mortality (0% and 6%, respectively) and did not differ significantly from patients who had not received inotuzumab (3% and 9%, respectively). Additionally, 3-year relapse-free survival and overall survival were not significantly different between groups — 54% in the inotuzumab group vs 75% in the noninotuzumab group (P = .07) and 68% vs 87%, respectively (P = .14).
• The 3-year cumulative incidence of relapse was higher among patients treated with inotuzumab (39% vs 16%; P = .02), although this difference was no longer significant among patients requiring fewer than three re-induction attempts (19% vs 17%; P = .91).
• Among the 34 patients who received defibrotide prophylaxis, only two discontinued it due to adverse reactions, including recurrent epistaxis or grade 2 gastrointestinal bleeding, both in the setting of concomitant thrombocytopenia.

IN PRACTICE

“Our findings suggest that defibrotide as SOS prophylaxis in patients previously treated with [inotuzumab ozogamicin] is well tolerated and associated with SOS-rates and severity comparable with those in patients without prior [inotuzumab ozogamicin] therapy, thereby representing a viable HSCT-strategy for pediatric patients with prior receipt of [inotuzumab ozogamicin],” the study authors wrote.

SOURCE

The study, led by Jonathan D. Paolino, Dana-Farber Cancer Institute, Division of Hematology/Oncology, Boston Children’s Hospital, Harvard Medical School, Boston, was published online on July 16, 2026, in Blood Advances.

LIMITATIONS

The study was limited by its retrospective single-center design. Because defibrotide prophylaxis was not randomly assigned, the study cannot establish that prophylaxis itself reduced SOS risk. It included only patients who successfully proceeded to HSCT, which may have introduced selection bias. Additionally, the small number of patients who received inotuzumab ozogamicin without defibrotide prophylaxis restricted the statistical power to draw definitive conclusions.

DISCLOSURES

The study received support from the Boston Children’s Hospital Translational Research Program and the Alex’s Lemonade Stand Foundation. Paolino disclosed receiving honoraria from Jazz Pharmaceuticals for activities unrelated to the work reported in this manuscript. The remaining authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.