Serious Hemorrhagic Complications After Successful Treatment of Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy With Defibrotide in Pediatric Patient With Myelodysplastic Syndrome

Abstract

Background: Transplant-associated thrombotic microangiopathy (TAM) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT). There is some evidence of endothelial injury playing a significant role in TAM development. The efficacy of defibrotide was demonstrated for prophylaxis and treatment of another HSCT-associated endothelial damage syndrome-liver veno-occlusive disease. The data for defibrotide usage in TAM are limited. Case Description: A 9-year old boy underwent HSCT from a matched unrelated donor for monosomy seven-associated myelodysplastic syndrome treatment. A myeloablative preparative regimen and post-transplant immunosuppression with cyclophosphamide on days +3 and +4 and a combination of tacrolimus with mycophenolate mofetil from day +5 were used. From day +61, sustained fever with progressive neurologic impairment and no evidence of infection was observed. On day +68, the patient developed severe TAM with acute kidney injury requiring renal replacement therapy (RRT). Defibrotide therapy 25 mg/kg/day was administered for 7 days with resolution of TAM symptoms. It was followed by multiple hemorrhagic episodes-epistaxis, hemorrhagic cystitis, and renal hemorrhage, which are presumed to be the complications of defibrotide therapy. Conclusion:Defibrotide could be an effective therapy for TAM, but adequate doses, duration of therapy, and drug safety profile both for pediatric and adult patients need to be evaluated by randomized prospective studies.

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy and the role of advanced practice providers and pharmacists

“…Another supportive treatment for HSCT-TMA, defibrotide is approved for the treatment of hepatic veno-occlusive disease, also known as sinusoidal obstruction syndrome, a complication following HSCT [63]. Retrospective analyses and case series of defibrotide therapy have reported responses in patients with HSCT-TMA [46,[64][65][66][67] and a prospective pilot study suggested prophylactic defibrotide use reduces the incidence of HSCT-TMA [68], but increased bleeding and hemorrhagic complications were reported with defibrotide use in these studies [65][66][67][68]. Historically, another approach to treat HSCT-TMA has been to withhold or modify calcineurin inhibitors [22], but recent data have shown that continuing immunosuppressants does not impact resolution of HSCT-TMA or survival in patients with HSCT-TMA.…”