Thrombotic Microangiopathy after Allogeneic Stem Cell Transplantation: A Comparison of Eculizumab Therapy and Conventional Therapy.

Abstract

We report the results of a single-center analysis of a cohort of 39 patients treated between 1997 and 2016 for transplantion-associated thrombotic microangiopathy. We evaluated 2 subgroups of patients: 24 patients treated between 1997 and 2014 who received conventional therapy and 15 patients treated with the complement-inhibiting monoclonal antibody eculizumab between 2014 and 2016. The conventional therapy group was treated predominantly with defibrotide alone or in combination with plasmapheresis or rituximab. Despite an initial response rate of 61%, only 4 patients (16%) were long-term survivors, 2 of whom had a low-risk thrombotic microangiopathy without multiorgan damage. Progression of thrombotic micorangiopathy and bacterial/fungal infections contributed equally to treatment failure. The overall response rate in the eculizumab group was significantly higher, at 93%. In addition, we were able to stop eculizumab treatment in 5 patients (33%), all of whom had high-risk thrombotic microangiopathy, due to sustained recovery. Despite the very good response in the eculizumab-treated group, we did not observe a significant improved overall survival, due primarily to a high rate of infection-related mortality (70%). Therefore, further studies are needed to identify the optimal therapeutic management approach for transplantation-associated thrombotic microangiopathy to improve its dismal outcome.

• Authors: Stephan R Bohl, Florian Kuchenbauer, Stefanie von Harsdorf, Nadine Kloevekorn, Stefan S Schönsteiner, Arefeh Rouhi, Phyllis Schwarzwälder, Hartmut Döhner, Donald Bunjes, Martin Bommer
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 23 Issue 12 Pg. 2172-2177 (Dec 2017) ISSN: 1523-6536 [Electronic] United States
• PMID: 28860002 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Polydeoxyribonucleotides
• defibrotide
• eculizumab

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Humans
• Infections (etiology)
• Middle Aged
• Polydeoxyribonucleotides (therapeutic use)
• Stem Cell Transplantation (adverse effects)
• Survival Analysis
• Thrombotic Microangiopathies (etiology)
• Transplantation, Homologous
• Treatment Outcome
• Young Adult