Risk of sinusoidal obstruction syndrome in allogeneic stem cell transplantation after prior gemtuzumab ozogamicin treatment: a retrospective study from the Acute Leukemia Working Party of the EBMT

Abstract

Gemtuzumab ozogamicin (GO) may increase the risk of sinusoidal obstruction syndrome (SOS) when used prior to allogeneic stem cell transplantation (HSCT). We assessed SOS incidence and outcomes after HSCT of 146 adults, with a median age of 50 years, previously receiving GO. SOS prophylaxis was used in 69 patients (heparin n=57, ursodeoxycholic acid n=8, defibrotide n=4). Cumulative incidence (CI) of SOS was 8% (n=11), with death in 3 patients. Median interval between last GO dose and HSCT was 130 days. Overall survival (OS) and SOS incidence did not differ for patients receiving GO ⩽3.5 months before HSCT and the others. CI of acute and chronic GVHD was 31% and 25%, respectively. Probability of OS and leukemia-free survival (LFS) at 5 years was 40% and 37%, respectively. Relapse incidence and non-relapse mortality were 42% and 21%, respectively. In multivariate analysis, active disease at HSCT was associated with relapse and worse LFS and OS (P<0.03). Liver abnormalities before HSCT correlated with worse OS (P<0.03). Use of low-dose GO prior to HSCT is associated with an acceptable SOS incidence. Prospective studies investigating the role and the utility of SOS prophylaxis are warranted.

Liver disease during and after hematopoietic stem cell transplantation in adults: a single-center Egyptian experience

“…In a similar study, Barba et al found that acute hepatic GVHD was found in 17% of patients who underwent allo-HSCT while chronic hepatic GVHD was found in 50% of their cohort [3]. Another multicenter retrospective study by Battipaglia et al that included 146 adults with AML and receiving allo-HSCT, the main cause of liver function abnormalities among patients were acute GVHD (31%), chronic GVHD at 2 years was 25% [10]. Regarding the type of conditioning regimen and hepatotoxicity, we found that busulfan-based conditioning regimens had a statistically significant hepatotoxic effect compared to non-busulfan conditioning regimens.…”

Risk Factors for Development of and Progression of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome

“…The novel antibody-drug conjugates GO and inotuzumab ozogamicin (INO), calicheamicin conjugates targeted against CD33 and CD22, respectively, were associated with increased risk of VOD/SOS in clinical trials [6,7,17,[50][51][52][53]. Black box warnings regarding the risk of hepatic VOD/SOS with use of each agent are included in their prescribing information documents [54,55].…”

“…Patients received GO at 6 mg/m 2 (first induction dose) and 3 mg/m 2 (second induction dose) and could receive up to 8 monthly infusions of 2 mg/m 2 thereafter. The risk of GO-associated VOD/SOS also was assessed retrospectively in 146 adults who received GO treatment for AML before undergoing HSCT [53]. Prophylaxis for VOD/SOS was used in 69 patients (heparin, n = 57; ursodeoxycholic acid, n = 8; defibrotide, n = 4).…”

Gemtuzumab ozogamicin and novel antibody-drug conjugates in clinical trials for acute myeloid leukemia

“…As reported in ALFA-0701, the incidence of VOD did not significantly differ between the GO and control arm [6 (4.6%) vs 2 (1.5%), p = 0.165], nor did the result of liver chemistry abnormalities [43]. In another study, out of 146 patients undergoing AlloSCT previously treated with GO, 11 (8%) developed VOD after transplantation, with death in 3 patients, comparable to the incidence of historical cohorts of patients not receiving GO [71]. Prophylaxis of VOD for high-risk patients with agents such as recombinant human soluble thrombomodulin might further lower the risk [72].…”