Intra-arterial methylprednisolone for the management of steroid-refractory acute gastrointestinal and hepatic graft versus host disease

Pathology and Laboratory Medicine, University of Rochester Medical Center, James P. Wilmot Cancer Center, Rochester, NY 14642, USA.
American Journal of Hematology (Impact Factor: 3.48). 08/2011; 86(8):712-4. DOI: 10.1002/ajh.22075
Source: PubMed
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    ABSTRACT: Acute gastrointestinal GvHD (GI-aGvHD) refractory to first-line treatment with systemic corticosteroids is resulting in death in the majority of patients. We prospectively assessed the feasibility and efficacy of regional intra-arterial steroid treatment in adult patients with severe (≥grade III) GI-aGvHD not responding to first-line treatment. Patients with more than +++ GI-aGvHD not responding to intravenous methylprednisolone at a dose of 2mg/kg/day were eligible for inclusion. Catheter guided intra-arterial steroid administration (IASA) was performed into the superior and inferior mesenteric artery. 12 consecutive patients with steroid-refractory grade III GI-aGvHD received IASA as second-line treatment. 83% of patients had gastrointestinal response including four patients (33%) with complete response at 28 days after IASA. 5/12 patients were alive at a median time of 531 days. Regional treatment of severe GVHD with IASA treatment seems to be a safe and effective second-line treatment for steroid-refractory GI-aGvHD in adult patients.
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    ABSTRACT: A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haema-tology (BCSH) and the British Society for Bone Marrow Transplantation (BSBMT) has reviewed the available litera-ture and made recommendations for the diagnosis and man-agement of acute graft-versus-host disease. This guideline includes recommendations for the diagnosis and grading of acute graft-versus-host disease as well as primary treatment and options for patients with steroid-refractory disease. The goal of treatment should be effective control of graft-versus-host disease while minimizing risk of toxicity and relapse. 1 An accountable transplant physician should be responsi-ble for supervising the treatment of patients with acute graft-versus-host disease (GvHD) (1C). 2 Clinical criteria should define acute GvHD and not purely time post-transplant (1B). 3 Clinical diagnosis is appropriate if the classical constella-tion of symptoms is present. Biopsies may be helpful if the diagnosis is unclear but should not delay manage-ment (1A). 4 At diagnosis, the extent of individual organ involvement and overall grade of acute GvHD should be documented, taking into account all organ involvement, as this has prognostic significance (1A). 5 The modified Seattle Glucksberg criteria (Przepiorka et al 1995) are recommended for grading (1A). 6 The management of grade 1 disease should include topi-cal therapy and optimizing levels of calcineurin inhibi-tors without the need for additional systemic immunosuppression (1C). 7 The use of systemic corticosteroids is recommended for first line therapy for grade II–IV GvHD (1A). 8 Two milligram/kg per day of methylprednisolone is rec-ommended as the starting dose for patients with grades III–IV GvHD (1A). 9 One milligram/kg per day of methylprednisolone is rec-ommended for patients with grade II GvHD (2B). 10 The use of 'nonabsorbable' steroids can be considered for acute intestinal GvHD in order to reduce the dose of systemic steroids (2B). 11 The following agents are suggested for use in the second line treatment of steroid-refractory acute GvHD: extra-corporeal photopheresis, anti-tumour necrosis factor a antibodies, mammalian target of rapamycin (mTOR) inhibitors, mycophenolate mofetil, interleukin-2 receptor antibodies (2C). 12 The following agents are suggested as third line treatment options in acute steroid-refractory GvHD: alemtuzumab, pentostatin, mesenchymal stem cells and methotrexate (2C).
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