TOPLINE

Children with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) treated with inotuzumab ozogamicin (InO) before hematopoietic stem cell transplant (HSCT) had sinusoidal obstruction syndrome (SOS) rates similar to those without prior InO when defibrotide prophylaxis was used. Among patients who received InO and defibrotide prophylaxis, 15% developed SOS, compared with 12% in the non-InO group.

METHODOLOGY

• Researchers analyzed 92 children, adolescents, and young adults with R/R B-ALL who underwent HSCT at a single center from January 2016 to October 2024, comparing outcomes between those who received InO during reinduction (n = 32) and those who did not (n = 60).
• A total of 32 patients received InO during reinduction before HSCT, with 81% (n = 26) receiving InO as the last therapy before transplant; all achieved complete remission (CR) with measurable residual disease (MRD) < 0.01% by flow cytometry (FCM) within 30 days before HSCT.
• Defibrotide prophylaxis at 6.25 mg/kg every 6 hours intravenous (IV) was administered to 81% (n = 26) of InO-treated patients and 13% (n = 8) of non-InO patients, typically starting at conditioning or stem cell infusion and continuing for a median of 23 days (range, 11-35 days).
• Primary outcomes included incidence of SOS (diagnosed using modified Seattle criteria, confirmed by pediatric European Society for Blood and Marrow Transplantation [pEBMT] criteria), nonrelapse mortality (NRM) at day 100, cumulative incidence of relapse (CIR), relapse-free survival (RFS), and overall survival (OS).
• Patients in the InO cohort were more heavily pretreated, with 31% (n = 10) in third remission (CR3) or higher and 31% (n = 10) requiring ≥3 reinduction attempts, compared with 13% (n = 8) and 5% (n = 3), respectively, in the non-InO group.

TAKEAWAY

• Among InO-treated patients who received defibrotide prophylaxis, the incidence of SOS was 15% (4 of 26 patients), similar to the 12% rate (7 of 60 patients) observed in the non-InO group (P = .61).
• In contrast, among InO-treated patients who did not receive defibrotide prophylaxis, the incidence of SOS was 50% (3 of 6 patients), significantly higher than the 12% rate (6 of 52 patients) in non-InO patients without prophylaxis (P = .01).
• NRM at 100 days was 0% in the InO group and 3% in the non-InO group (P = .54), with 3-year NRM of 6% and 9%, respectively.
• The 3-year CIR was higher in the InO group at 39% compared with 16% in the non-InO group (P = .02); however, when restricted to patients requiring < 3 reinduction attempts, CIR was similar between groups (19% vs 17%; P = .91).

IN PRACTICE

"These results support the use of InO for children with relapsed or refractory B-ALL and suggest that defibrotide prophylaxis may reduce the incidence of SOS during HSCT after InO," wrote the authors of the study.

SOURCE

The study was led by Jonathan D. Paolino, Dana-Farber Cancer Institute, Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School in Boston. It was published online on July 20 in Blood Advances.

LIMITATIONS

The retrospective design and small sample size, particularly among InO-treated patients who did not receive defibrotide prophylaxis (n = 6), limit definitive conclusions. Modified Seattle criteria were used for SOS diagnosis during most of the study period, which may differ from contemporary pediatric EBMT criteria; comprehensive data on refractory thrombocytopenia were not uniformly available across the cohort. The study cannot distinguish whether defibrotide reduced SOS incidence or severity, and selection bias exists as only patients achieving CR proceeded to HSCT.

DISCLOSURES

The study was supported by the Boston Children's Hospital Translational Research Program and the Alex's Lemonade Stand Foundation. One author reported receiving honoraria from Jazz Pharmaceuticals for activities unrelated to this work. The remaining authors reported 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.