Prajwal Dhakal1, Smith Giri2, Ranjan Pathak3, Vijaya Raj Bhatt4. 1. 1 Department of Medicine, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal. 2. 2 Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA. 3. 3 Department of Medicine, Reading Health System, West Reading, PA, USA. 4. 4 Department of Internal Medicine, Division of Hematology-Oncology, University of Nebraska Medical Center, Omaha, NE, USA.
Abstract
INTRODUCTION: Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare entity with no standard of care and high mortality, despite the use of plasma exchange. METHODS: Using specific search terms, all cases having TA-TMA treated with eculizumab and indexed in MEDLINE (English language only) by November 2014 were reviewed. RESULTS: A total of 26 cases, 53% men, had a median age of 33 years (range 2-61). Transplant-associated thrombotic microangiopathy occurred after stem-cell transplant (35%) or solid-organ transplant (65%), frequently associated with the use of cyclosporine or tacrolimus (96%). A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS 13) level was always >10%. After TA-TMA diagnosis, the following drug adjustments were made: discontinuation of cyclosporine or tacrolimus in 45%, dose reduction in another 27%, continuation of the drugs in 23%, and switch from cyclosporine to tacrolimus in remaining 5%. Plasma exchange was performed in ∼43%. The median interval between transplant and initiation of eculizumab was 63 days (range 11-512). A median of 5.5 doses (range 2-21) of eculizumab was utilized with 92% response occurring after a median of 2 doses (range 1-18). At a median follow-up of 52 weeks (range 3-113), the survivors (92%) were doing well. CONCLUSION: Within the limits of this retrospective analysis, our study demonstrates that eculizumab use may result in high response rate and 1-year survival in patients with TA-TMA refractory to discontinuation of calcineurin inhibitor and plasma exchange.
INTRODUCTION: Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare entity with no standard of care and high mortality, despite the use of plasma exchange. METHODS: Using specific search terms, all cases having TA-TMA treated with eculizumab and indexed in MEDLINE (English language only) by November 2014 were reviewed. RESULTS: A total of 26 cases, 53% men, had a median age of 33 years (range 2-61). Transplant-associated thrombotic microangiopathy occurred after stem-cell transplant (35%) or solid-organ transplant (65%), frequently associated with the use of cyclosporine or tacrolimus (96%). A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS 13) level was always >10%. After TA-TMA diagnosis, the following drug adjustments were made: discontinuation of cyclosporine or tacrolimus in 45%, dose reduction in another 27%, continuation of the drugs in 23%, and switch from cyclosporine to tacrolimus in remaining 5%. Plasma exchange was performed in ∼43%. The median interval between transplant and initiation of eculizumab was 63 days (range 11-512). A median of 5.5 doses (range 2-21) of eculizumab was utilized with 92% response occurring after a median of 2 doses (range 1-18). At a median follow-up of 52 weeks (range 3-113), the survivors (92%) were doing well. CONCLUSION: Within the limits of this retrospective analysis, our study demonstrates that eculizumab use may result in high response rate and 1-year survival in patients with TA-TMA refractory to discontinuation of calcineurin inhibitor and plasma exchange.
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