High-Dose Methylprednisolone for Veno-Occlusive Disease of the Liver in Pediatric Hematopoietic Stem Cell Transplantation Recipients

Abstract

Veno-occlusive disease (VOD) of the liver is a well-recognized serious complication of hematopoietic stem cell transplantation (HSCT), with few successful treatment modalities available for severe disease. Some reports have demonstrated success in adults with the use of high-dose steroid therapy, but experience in the pediatric population is lacking. We retrospectively reviewed HSCT patients treated at our institution since 2003 and identified 15 (2.4%) who developed VOD. Of these, nine (60%) were treated with intravenous high-dose methylprednisolone (500 mg/m2 per dose every 12 hours for six doses). Steroid therapy was initiated at or before first ultrasound evidence of reversal of portal venous flow and before meeting criteria for initiation of defibrotide therapy. Four patients were also treated with defibrotide starting 2 to 5 days after initiation of steroids. Eight of nine patients (88%) with VOD were diagnosed with multiorgan failure. Response to high-dose steroid therapy as defined by decrease in bilirubin by 50% in 10 days from therapy initiation was noted in six of nine patients (67%), occurring within 3 to 6 days of steroid therapy. Two patients died from multiorgan failure due to VOD. Seven survivors of VOD recovered at the median 6 days (range, 5 to 38) from VOD diagnosis. Overall, VOD survival as a group was 78%; however, survival among responders was 100%. No serious toxicities related to high-dose steroid therapy were observed. We conclude that high-dose steroid therapy if initiated early may reverse VOD of the liver in pediatric HSCT patients, abrogating the need for defibrotide therapy with its associated toxicities and regulatory difficulties.

The use of defibrotide in blood and marrow transplantation

“…84,85 The overall incidence of VOD/SOS in patients undergoing HSCT was estimated to be 13.7% (range, 0%-62%) in a pooled analysis of 135 studies. 77 In a single-institution study, the reported incidence was 11.5% (Baltimore criteria) and 13.8% (modified Seattle criteria) 75 ; MOD/MOF occurred in ;36% of patients with VOD/SOS diagnosed by Baltimore criteria and 22% by modified Seattle criteria.…”

Sinusoidal Obstruction Syndrome (Hepatic Veno-Occlusive Disease)

“…61 A recent pediatric retrospective study described by Myers et al, 2013, 9 patients who received methylprednisolone. 125 Eight of these patients had multi-organ failure secondary to SOS. Response was defined as a 50% reduction in bilirubin level by 10 days after the commencement of therapy.…”

“…Overall survival was 78%. 125 Methylprednisolone may be considered for the use in the treatment of SOS with the appropriate caveats of caution regarding infection.…”

Defibrotide for the Treatment of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome with Multiorgan Failure

“…The joint BCSH/BSBMT guideline does not recommend use of tPA for treatment of VOD/SOS due to the associated risk of bleeding [21]; guidelines from the European School of Haematology (ESH)-EBMT note that while tPA may be effective in some patients, it is contraindicated in those with MOF, hemorrhage or severe hypertension [33]. In two clinical studies in patients with VOD/SOS, administration of IV high-dose methylprednisolone (500 mg/m 2 or kg every 12 h) achieved response in the majority of patients, with overall Day +100 survival rates of 58% [41] and 78% [42]. Overall, given the associated risk of infection and limited evidence of its efficacy, this treatment option (used with commensurate caution) may be most appropriate for patients lacking therapeutic alternatives [32].…”