The Incidence of Veno-Occlusive Disease Following Allogeneic Hematopoietic Stem Cell Transplantation Has Diminished and the Outcome Improved over the Last Decade

Abstract

The evolution of the incidence, morbidity, and mortality of veno-occlusive disease (VOD) was analyzed in 845 allogeneic hematopoietic stem cell transplantations (allo-HSCTs) performed over 24 years. A total of 117 patients and 73 patients developed VOD following the Seattle and the Baltimore diagnostic criteria, respectively (cumulative incidence 13.8% and 8.8%). The cumulative incidence was significantly higher in the period 1985 to 1996 than in 1997 to 2008 (11.5% vs 6.5%; P = .01). This decline was because of the low incidence of VOD among reduced-intensity conditioning-HSCT (RIC-HSCT) (2.1%) and the reduction among those receiving myeloablative-HSCT from unrelated donors (32.7% vs 10.5%, P = .001). A total of 35 patients had severe VOD (26 with multiorgan failure [MOF]), and 20 died by VOD (cumulative mortality rate 17.3%, Seattle, or 22.5%, Baltimore). The mortality declined since 1997 (from 22% to 9%; P = .06, Seattle, and from 36% to 14%; P = .04, Baltimore), with the introduction of defibrotide being the only relevant change in the management of patients. This occurred even though the severity of VOD was similar in both periods. Among those with MOF, only 2 of 8 (25%) receiving defibrotide died versus 14 of 18 (78%) receiving other treatments (P = .007). Myeloablative conditioning, previous liver disease, poor performance status, and alternative donors were the variables with higher impact on VOD development. In summary, although VOD remains a dreaded early complication of HSCT, technical and therapeutic progress in recent decades have notably reduced its incidence and improved the outcome.

Salvage therapy with high-dose cytarabine and mitoxantrone in combination with all-trans retinoic acid and gemtuzumab ozogamicin in acute myeloid leukemia refractory to first induction therapy

“…In our trial, a dosage of 3 mg/m 2 had only a modest impact on toxicity, especially with regard to the development of SOS directly after salvage therapy as well as after transplantation, with a rate of moderate/severe SOS after transplantation of 8.5%, which is expected in this patient population. 30,31,37,38 Thus, in contrast to previous data showing an enormously increased incidence of SOS (64%) by pre-treatment with GO (6 mg/m 2 or 9 mg/m 2 ) in a 3.5-month period prior to transplant, 39 we were able to show that salvage therapy including GO in a dosage of 3 mg/m 2 is safe and can be followed by allogeneic HCT without increasing the rate of SOS. Whether an increment of the GO dosage by using fractionated administration, 40,41 comparable to successful attempts in first-line therapy, 35 is safe in terms of SOS and even more effective compared to our GO-A-HAM regimens remains elusive.…”

Sinusoidal Obstruction Syndrome (Hepatic Veno-Occlusive Disease)

“…28 Although initial reports of SOS incidence were in the 60% range, 17 a more recent meta-analysis of 135 studies performed between 1979 and 2007 place the overall mean incidence of SOS following HSCT at 13.7% (95% confidence interval = 13.3%-14.1%) 57 In one report, the cumulative incidence was significantly higher 20 years ago (1985)(1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996) than in more recent years (1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008), attributed to reduced-intensity conditioning regimes for HSCT, and the reduction in use of unrelated donors for HSCT. 58 Onset of SOS is characterized by painful hepatomegaly, jaundice, weight gain, and ascites. Severe SOS is typically associated with multiorgan failure (MOF) and high mortality rates (>80%) [57][58][59] The sudden weight gain and the development of hepatomegaly and tenderness typically occur on day 0 or 1 following HSCT, or 8-10 days after initiation of cytoreductive therapy.…”

“…58 Onset of SOS is characterized by painful hepatomegaly, jaundice, weight gain, and ascites. Severe SOS is typically associated with multiorgan failure (MOF) and high mortality rates (>80%) [57][58][59] The sudden weight gain and the development of hepatomegaly and tenderness typically occur on day 0 or 1 following HSCT, or 8-10 days after initiation of cytoreductive therapy. From the standpoint of clinical parameters, when serum bilirubin values exceed 15 mg/dl and weight gains approach 10-15 kg, mortality exceeds 90%.…”

“…[133][134][135][136][137] The reported incidence of SOS following allogeneic hematopoietic stem cell transplantation has diminished and the outcome improved over the last decade. 138 This has been attributed to reduced-intensity conditioning HSCT (RIC-HSCT) for patients myeloablative-HSCT from unrelated donors.…”

Toxicity and efficacy of busulfan and fludarabine myeloablative conditioning for HLA-identical sibling allogeneic hematopoietic cell transplantation in AML and MDS

“…The incidence of VOD with BuFlu is generally lower than 5%, and this effect is also in agreement with the reported observation of a reduction in the incidence of VOD over time. 42 VOD is expected to be less frequent and severe with the use of i.v. compared with oral Bu, with RIC compared with MAC, and with BuFlu compared with BuCy conditioning.…”