Approaching treatment of transplant-associated thrombotic Microangiopathy from two directions with Eculizumab and transitioning from Tacrolimus to Sirolimus

BACKGROUND In the past, conventional treatment strategies for transplant-associated thrombotic microangiopathy (TA-TMA) have not proven to be very effective. Recently, eculizumab which is a humanized monoclonal antibody that works as a terminal complement inhibitor has demonstrated promise in the treatment landscape of TA-TMA. METHODS AND MATERIALS This was a single-center retrospective analysis of 20 consecutive adult patients with TA-TMA: 10 patients who received conventional therapy and 10 patients who received eculizumab-based therapy. These patients had undergone allogeneic HSCT at MD Anderson Cancer Center between August 2011 and September 2016. RESULTS When comparing the treatment outcomes in the two cohorts, none of the patients in the conventional therapy group obtained a hematologic or complete response according to our response criteria whereas seven patients in the eculizumab group achieved a hematologic response with one patient achieving a complete response with organ recovery. In addition, overall survival at the end of assessment was 60% in the eculizumab cohort and 30% in the conventional cohort. One major difference in practice at our institution versus previously published studies is the management of immunosuppression. In a majority of patients, tacrolimus was continued or transitioned to sirolimus for GVHD prophylaxis. CONCLUSION Response rates and survival were improved for patients who were transitioned to sirolimus, so a two-pronged approach of inhibiting complement along with providing an alternative effective immunosuppressive agent may be beneficial in the treatment of early onset TA-TMA.