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

Frontiers in Pediatrics

Irina Shipitsina¹  Dmitry Balashov¹  Alexei Maschan¹  Alexandra Laberko²  Anna Shcherbina²  Igor Khamin³  Marina Aksenova⁵ 

[1] Hematopoietic Stem Cell Transplantation, Dmitry Rogachev National Medical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia;Immunology, Dmitry Rogachev National Medical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia;Intensive Care, Dmitry Rogachev National Medical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia;Nephrology, Dmitry Rogachev National Medical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia;Nephrology, Y. Veltischev Research and Clinical Institute for Pediatrics at N. Pirogov Russian National Research Medical University, Moscow, Russia;

关键词: hematopoietic stem cell transplantation;    myelodysplastic syndrome;    thrombotic microangiopathy;    defibrotide;    renal bleeding;   

DOI  :  10.3389/fped.2020.00155

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown