Prognosis of Veno-Occlusive Disease after Stem Cell Transplantation in the DF-VOD Trial. On behalf of the DF-VOD Investigators:.
Authors: Barbui Tiziano , Caruso Vanesa , Tognoni Gianni , Marchioli Roberto 
Published: October 2019

Hepatic veno-occlusive disease (VOD) is a severe complication occurring in patients undergoing intensive chemotherapy and stem cell transplantation (SCT). Its therapy is based on general supportive procedures; however, even if these measures improve with time and new specific therapies are now available, chances of success continue to be scarce, and day + 100 mortality exceeds 50% in current series.

Methods: In the DF-VOD trial, patients are being randomized to receive defibrotide (DF) or no treatment other than supportive and are followed-up for 100 days. Diagnosis of VOD is based on the Baltimore Criteria, and patients who do not meet them but have a biopsy or hemodinamically proven VOD are also eligible. Complete Response (CR) is defined as a bilirubin < 2 mg/dl and complete resolution of any other end-organ dysfunction. In this report, principal characteristics and the outcome of the whole cohort are described. Pre-SCT (age, gender, primary disease, conditioning, donor type) and clinical and laboratory characteristics at diagnosis of VOD (days from SCT to VOD, bilirubin and AST/ALT levels, and the presence of ascites and multiorgan failure (MOF)) were analyzed as prognostic factors by logistic regression models adjusted for treatment and other principal confounders.

Results: Fifty-eight patients were randomized since October 2001, but 8 patients were excluded from the analysis because of missing data. Their principal characteristics at randomization and outcome are shown in table 1. The outcome of this cohort was found to be similar to that of Richardson’s cohort of 78 patients, all treated with defibrotide, in which CR was 49% and day +100 survival was 42% (Blood2003; 102:193a). Variables significantly associated with survival are shown in table 2.

Conclusions: History of previous SCT, severe liver dysfunction denoted by high levels of bilirubin and AST/ALT, and the involvement of other organs seem to be independent risk factors for mortality in patients with VOD. The low survival in this population underlines the need of new treatment strategies. Randomization of patients in the DF-VOD trial is going on to produce clear evidence on the efficacy of defibrotide in this disease.

Patients’ characteristics and outcome

N = 50 Gender (% males) 30 (60) Age at randomization (SD) 36.6 (16.1) Days from SCT to VOD (SD) 13 (12) Primary disease: (%) ---Hematological malignancy 47 (94) --- Other 3 (6) Conditioning: (%)--- BUCY 16 (32) --- CY + TBI 16 (32) --- Other 18 (36) Type of donor: (%)--- HLA-identical / Syngenic 27 (54) --- Autologous 5 (10) --- HLA-mismatched 4 (8) --- Unrelated 14 (28) Previous SCT (%) 13 (26) Ascites 24 (48) Bilirubin (mg/dl), median (range) 6.0 (2.0-30.0) AST/ALT > 40 U/L (%) 24 (48) MOF at diagnosis (%) 29 (58) Complete Response (%) 19 (38) Day + 100 survival (%) 17 (34) -- Adults 15/45 (33) -- Pediatrics 2/5 (40)

Characteristics associated with mortality in multivariate analyses

N (%) RR (95% IC) P Previous SCT 13 (26) 12.8 (1.14-143.7) 0.0390 Bil < 6 mg/dl AND AST/ALT < 40 U/L 17 (34) 1.00 Bil ≥ 6 mg/dl OR AST/ALT ≥ 40 U/L 17 (34) 2.26 (0.40-12.8) 0.3565 Bil ≥ 6 mg/dl AND AST/ALT ≥ 40 U/L 16 (32) 16.0 (1.92-133.4) 0.0103 Hepatic + one additional organ dysfunction 11 (22) 2.81 (0.43-18.4) 0.2811 Hepatic + ≥ 2 additional organ dysfunction 18 (36) 10.4 (1.38-77.6) 0.0231