Sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation: Incidence, risk factors and outcomes

Abstract

This retrospective study was conducted in Japan to determine the incidence, risk factors and outcomes of sinusoidal obstruction syndrome (SOS) after allogeneic hematopoietic stem cell transplantation (HSCT). Among 4290 patients undergoing allogeneic HSCT between 1999 and 2010, 462 were diagnosed with SOS according to the Seattle criteria (cumulative incidence, 10.8%). The cumulative incidence of SOS diagnosed by the modified Seattle criteria was 9.3%. Of 462 patients, 107 met the Baltimore criteria and 168 had severe SOS with renal and/or respiratory failure. The median onset for SOS was 12 days after HSCT (range, À 2-30). Overall survival at day 100 was 32% for SOS and 15% for severe SOS. Multivariate analyses showed that significant independent risk factors for SOS were the number of HSCTs, age, performance status, hepatitis C virus-seropositivity, advanced disease status and myeloablative regimen. SOS was highly associated with overall mortality (hazard ratio, 2.09; P o 0.001). Our retrospective survey showed that the cumulative incidence of SOS in Japan was 10.8%, similar to that previously reported in Western countries, and that the overall survival of patients who developed SOS was low. Furthermore, several risk factors were identified. Preventive and therapeutic strategies for high-risk SOS patients must be established to improve overall survival.

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

“…Studies that evaluated risk factors for VOD/SOS in large HSCT recipient populations over the past 5 to 7 years vary in consistency with previous data and reveal potential risk factors that have not previously been noted [21,23,26,[36][37][38][39] (Table 5). Among 10 such studies identified for this review, with total numbers ranging from 75 to 5072 patients, incidence of VOD/ SOS ranged from 2.0% (lowest incidence was diagnosed with EBMT criteria) to 30.7% (Table 5).…”

“…Identification of patients at highest risk for VOD/SOS may be key to prompt diagnosis and optimal management of VOD/ SOS [25]. Several analyses have shown an association between diagnosis using the modified Seattle criteria and better outcomes versus outcomes in patients diagnosed with the more stringent Baltimore criteria [23,26,27]. In a retrospective multicenter observational study of allogeneic HSCT recipients in Japan (n = 4290), VOD/SOS with MOD was associated with higher levels of total bilirubin, ascites, and encephalopathy at diagnosis, and patients who met the Baltimore criteria had lower rates of complete response to treatment (resolution of VOD/SOS and, if present, MOD) and overall survival compared with those who met the Seattle criteria alone in either the presence or absence of MOD (P < .001 for all comparisons) [26].…”

“…Several analyses have shown an association between diagnosis using the modified Seattle criteria and better outcomes versus outcomes in patients diagnosed with the more stringent Baltimore criteria [23,26,27]. In a retrospective multicenter observational study of allogeneic HSCT recipients in Japan (n = 4290), VOD/SOS with MOD was associated with higher levels of total bilirubin, ascites, and encephalopathy at diagnosis, and patients who met the Baltimore criteria had lower rates of complete response to treatment (resolution of VOD/SOS and, if present, MOD) and overall survival compared with those who met the Seattle criteria alone in either the presence or absence of MOD (P < .001 for all comparisons) [26]. Similarly, retrospective data from an expanded-access study of defibrotide for treating patients with VOD/SOS (with or without MOD) showed lower day +100 overall survival in HSCT recipients diagnosed by the Baltimore criteria (58.9%) compared with those diagnosed by the modified Seattle criteria (72.3%) or biopsy (67.6%) [23].…”

“…Transplantation-related factors associated with an increased risk of VOD/SOS in adult HSCT recipients following multivariate analysis included the use of horse antithymocyte globulin [37], oral versus i.v. serum level-adjusted administration of busulfan (adults and adolescents) [38], myeloablative conditioning regimens (total body irradiation-based and busulfan-based) and 2 or more HSCTs [26], use of busulfan-thiotepa conditioning in adults with VOD/SOS requiring pharmacologic treatment with at least analgesics or diuretics [36], and increased trough serum tacrolimus level (above the target range of 5 to 10 ng/mL) [21]. In children, the use of busulfan in conditioning regimens versus nonuse of busulfan was an independent risk factor for VOD/ SOS, diagnosed with the EBMT pediatric criteria in a large study (n = 5072), associated with a cumulative incidence of 5.1% (95% CI, 4.1% to 6.3%; P < .001) [30].…”

Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure

“…22 Moreover, a large Japanese HSCT registry analysis of 4290 patients found a rate of severe VOD/SOS of 3.9%. 24 Although the difference between groups in day 1100 survival was statistically significant, day 1180 survival did not reach statistical significance. Importantly, all deaths in both groups after day 1100 were considered to be related to a cause other than VOD/SOS.…”