Treatment of Steroid-Refractory Acute Graft Versus Host Disease with Low Dose Combination Monoclonal Antibody Therapy: A Pilot Study.

Severe (Grade III–IV) acute graft versus host disease (aGVHD) is a serious complication of allogeneic haemopoietic stem cell transplantation. Patients not responding to high dose corticosteroids have a very poor prognosis (60–90% mortality). Previous second line agents, such as anti-thymocyte globulin, have had limited success in controlling steroid-refractory aGVHD. Recently monoclonal antibodies that target cytokines (TNF and IL-2) have been trialled, with several case series reporting responses to high dose infliximab (10mg/kg, x1-9 doses) and daclizumab (1mg/kg, x5-8 doses), alone or in combination. Here we report the results of a pilot study using reduced-dose infliximab and daclizumab, along with strict antimicrobial prophylaxis, for refractory aGVHD. The aim was to maintain the efficacy of monoclonal antibody therapy whilst reducing the infectious complications seen in previous series.

Since May 2003 we have treated 10 allogeneic transplant patients with one or both of the monoclonal antibodies. All had failed a minimum of 3 days methylprednisolone 2mg/kg/day, started a median of 35 days post-transplant. The first four patients received infliximab 10mg/kg, x2-3 doses. Two of four had a complete response with one patient alive 15 months after antibody treatment. The remaining three died of opportunistic infections. Following this study, a second cohort of patients (n=6) were given low dose, combination therapy (infliximab 5mg/kg, x2 doses and daclizumab 1mg/kg, x4 doses). 5/6 patients had complete resolution of aGVHD and 5/6 are alive at a median of 130 days post-treatment. One patient died of MRSA pneumonia despite resolution of GVHD. The remaining 5 patients have had minimal and manageable infectious complications whilst on strict prophylactic regimens. In conclusion, low dose combination monoclonal antibody therapy appears to be a promising and safe treatment for refractory aGVHD.