Infliximab for the Treatment of Severe Steroid Refractory Acute Graft-versus-host Disease in Three Patients after Allogeneic Hematopoietic Transplantation

Abstract

Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic peripheral blood stem cell transplantation (PBSCT). Patients with severe aGVHD not responding to treatment with steroids have a poor prognosis. We treated three patients with severe aGVHD refractory to steroids with infliximab. Patients (MDS 1, NHL 1, ALL 1) developed grade II-IV GVHD at a median of 13 days (range 9-17) after non-myeloablative PBSCT (HLA mismatched). All patients had received treatment with high-dose steroids for a median of 7 days (range 7-10) in addition to mycophenolate mofetil (MMF) (one). Infliximab was given in 3 weekly doses of 5 mg/kg. In one of three patients a partial resolution of diarrhea and minor improvement of skin were observed. One patient died with refractory GVHD. Infliximab is apparently an effective drug for the treatment of aGVHD, but can be more effective at doses of 5 mg/kg or higher and/or by administering it repeatedly every week.

Infliximab for GVHD therapy in children

“…[12][13][14][15][16][17][18] Only a small number of pediatric patients have been reported. We review our experience with infliximab treatment of 24 children with steroid-resistant GVHD.…”

Treatment of steroid-resistant acute graft-versus-host disease with daclizumab and etanercept

“…[22][23][24] Results from phase II trials of treatment of aGVHD with the monoclonal humanized antibody infliximab suggest a significant response rate, especially in gut GVHD, hampered by a high mortality due to infectious complications. [25][26][27][28][29][30] Etanercept is a TNF-receptor fusion protein which, unlike infliximab, does not eliminate TNF-positive cells via antibody-dependent cytotoxicity (ADCC) and induction of monocyte apoptosis. The elimination of TNF-positive cells has been associated with an increased rate of infectious mortality.…”

Combination antithymocyte globulin and soluble TNFα inhibitor (etanercept) +/− mycophenolate mofetil for treatment of steroid refractory acute graft-versus-host disease

“…[7][8][9][10][11][12][13]19 Etanercept is a fusion protein consisting of two identical chains of the human TNFreceptor p75 monomer fused with the Fc domain of human IgG1. It binds to soluble TNFa, neutralising its activity.…”

“…[2][3][4][5][6] The second approach is based upon blockage of cytokine pathways involved in the pathogenesis of acute GVHD, by use of antibodies inhibiting especially tumor necrosis factor-a (TNFa) (etanercept, infliximab) and interleukin-2 (dacluzimab, basiliximab) pathways. [7][8][9][10][11][12][13][14][15][16][17] We have previously reported on use of tacrolimus and ATG for steroid refractory acute GVHD. 2 In brief, although this combination appeared efficacious in patients with refractory cutaneous GVHD (100% response rate; 80% survival), for patients with refractory visceral GVHD, outcome was significantly inferior (60% response rate; 20% survival).…”