Defibrotide for the treatment of hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation

Corbacioglu, Selim; Kernan, Nancy A.; Lehmann, Leslie; Brochstein, Joel A.; Revta, Carolyn; Grupp, Stephan A.; Martin, Paul L.; Richardson, Paul G.

doi:10.1586/ehm.12.18

Cited by 42 publications

(33 citation statements)

References 71 publications

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“…Current standard treatments for VOD consist of supportive measures, including analgesia, diuresis, transfusional and ventilatory support, and renal replacement therapy [6]. Therapeutic options targeting the underlying etiology, which remains poorly understood, are few.…”

Section: Introductionmentioning

confidence: 99%

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

Myers

Lawrence

Marsh

et al. 2013

Biology of Blood and Marrow Transplantation

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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.

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Section: Introductionmentioning

confidence: 99%

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

Myers

Lawrence

Marsh

et al. 2013

Biology of Blood and Marrow Transplantation

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“…Total serum bilirubin is often used as a marker for response to treatment with defibrotide, as discussed in studies by Ho et al 7 and Richardson et al 8 However some patients with VOD may not have hyperbilirubinemia but still have all the other features consistent with VOD. 9,10 In a recent study by Myers et al, 10 five patients had a bilirubin of ⩽ 2 mg/dL at the time of diagnosis of VOD and reversal of portal venous flow (PVF) by ultrasonography; two of these continued to have a bilirubin of o 2 mg/dL. 10 There have been few studies focusing specifically on anicteric VOD.…”

mentioning

confidence: 99%

Anicteric veno-occlusive disease after hematopoietic stem cell transplantation in children

Naples

Skeens

Auletta

et al. 2015

Bone Marrow Transplant

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“…The incidence of veno-occlusive disease (VOD) in children following HSCT ranges from 11 to 60%, giving a mean incidence in children of approximately 25% compared with an incidence of 13.7% across all age groups, as recently summarized by Coppell et al 39,40 . VOD as defined by the Baltimore criteria 41 was diagnosed in a total of 6 of our patients.…”

Section: Resultsmentioning

confidence: 99%

Single-Agent Post-Transplantation Cyclophosphamide as Graft-versus-Host Disease Prophylaxis after Human Leukocyte Antigen–Matched Related Bone Marrow Transplantation for Pediatric and Young Adult Patients with Hematologic Malignancies

Jacoby

Chen

Loeb

et al. 2016

Biology of Blood and Marrow Transplantation

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High dose cyclophosphamide given after HLA-matched related and unrelated allogeneic bone marrow transplantation (BMT) for patients with hematologic malignancies is effective single agent graft-versus-host disease (GVHD) prophylaxis in adults. Data describing outcomes for pediatric and young adult patients has not been reported. Between the years 2007-2013, 29 pediatric and young adult patients age ≤ 21 years of age treated at our institution for high-risk hematologic malignancies underwent myeloablative HLA-matched related T cell replete BMT. Eleven patients received post-transplant cyclophosphamide (PTCy) as single agent GVHD prophylaxis and were followed prospectively. Eighteen patients received calcineurin inhibitor (CNI)-based standard GVHD prophylaxis and were studied retrospectively as a control group. No acute GVHD developed in patients receiving PTCy, while patients receiving CNI-based GVHD prophylaxis had a cumulative incidence of grade II-IV and grade III-IV acute GVHD of 27% and 5% respectively. No patients receiving PTCy developed chronic GHVD, compared to one in the control group. Two-year overall survival was similar between the two groups (54% PTCy vs 58% CNI-based prophylaxis), as was event-free survival (42% PTCy vs 47% CNI-based). The 5 year cumulative incidence of relapse was 58% for PTCy and 42% for CNI-based GVHD prophylaxis (p=0.45). These results suggest that PTCy is a safe and efficacious method of GVHD prophylaxis following an HLA-matched related BMT in the pediatric and young adult population that affords patients to be off all post-transplant immunosuppression on day +5.

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Defibrotide for the treatment of hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation

Cited by 42 publications

References 71 publications

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

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

Anicteric veno-occlusive disease after hematopoietic stem cell transplantation in children

Single-Agent Post-Transplantation Cyclophosphamide as Graft-versus-Host Disease Prophylaxis after Human Leukocyte Antigen–Matched Related Bone Marrow Transplantation for Pediatric and Young Adult Patients with Hematologic Malignancies

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