Timing of Allogeneic Hematopoietic Cell Transplantation After Inotuzumab Ozogamicin Influences Sinusoidal Obstruction Syndrome and Survival in Relapsed/Refractory B-ALL.
In a retrospective multicenter cohort of 107 InO-responsive patients aged ≥15 years with relapsed/refractory B-ALL, transplantation within 50 days of the last InO dose and greater InO exposure were associated with more SOS, non-relapse mortality, and inferior survival.
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In a retrospective multicenter cohort of 107 InO-responsive patients aged ≥15 years with relapsed/refractory B-ALL, transplantation within 50 days of the last InO dose and greater InO exposure were associated with more SOS, non-relapse mortality, and inferior survival.
Research significance
The study provides observational evidence that a shorter InO-to-HCT interval and greater InO exposure identify patients at increased post-transplant risk; it supports—but does not prove—the hypothesis that delaying HCT beyond 50 days when clinically feasible, limiting InO cycles, or adapting conditioning and monitoring could reduce SOS and improve outcomes.
Source abstract
BACKGROUND: Inotuzumab ozogamicin (InO) is widely used as a bridge to allogeneic hematopoietic cell transplantation (HCT) in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). However, post-transplant sinusoidal obstruction syndrome (SOS) remains a major complication, and the optimal timing of HCT after InO exposure is not established. OBJECTIVE: To evaluate the impact of InO exposure and timing between InO and HCT on transplant outcomes, with a focus on SOS, non-relapse mortality (NRM), and survival. STUDY DESIGN: We conducted a retrospective multicenter observational study across 21 Spanish transplant centers within the Grupo Español de Trasplante Hematopoyético y Terapia Celular (GETH-TC). We included 107 adolescents and adults (≥15 years) with R/R B-ALL who achieved response to InO and proceeded to allogeneic HCT between January 2017 and June 2025. Patients were excluded if refractory to InO. Clinical, treatment, transplant, and outcome data were prospectively collected in a centralized REDCap database. SOS, graft-versus-host disease (GVHD), engraftment, relapse, and survival outcomes were analyzed. Multivariable Cox and Fine-Gray models were used to identify risk factors. RESULTS: The median age was 39 years; 53% were male. Most patients achieved CR prior to HCT, and 74% were MRD-negative. The median interval from last InO dose to HCT was 49 days, and 57% received ≥2 cycles of InO. Conditioning was TBI-based in 54%, and 74% received post-transplant cyclophosphamide. SOS occurred in 34.6% of patients, with 79% classified as severe or very severe. The 120-day cumulative incidence of SOS was 34%, and 27% for severe/very severe SOS. In multivariable analysis, an interval ≤50 days between InO and HCT (HR 3.15), male sex (HR 2.86), and myeloablative TBI-based conditioning (HR 2.47) were independently associated with increased risk of SOS. Higher EASIX scores were also predictive of SOS. Receipt of >2 InO cycles and a short InO-to-HCT interval were associated with increased NRM. SOS was associated with higher NRM (HR 2.78). MRD positivity prior to HCT was associated with higher relapse risk (HR 2.27). At 2 years, OS, LFS, and GRFS were 51%, 42%, and 33%, respectively. A short InO-to-HCT interval (≤50 days), >2 cycles of InO, MRD positivity, and higher EASIX were associated with inferior survival outcomes. CONCLUSIONS: In patients with R/R B-ALL undergoing allogeneic HCT after InO, SOS is frequent and clinically significant. A short interval between InO and HCT (≤50 days) and greater InO exposure are independently associated with increased SOS, NRM, and inferior survival. These findings identify potentially modifiable, clinically actionable factors that may improve transplant outcomes.