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Recovery from life-threatening transplantation-associated thrombotic microangiopathy using eculizumab in a patient with very severe aplastic anemia

Bone Marrow Transplantation volume 49, pages 1116–1118 (2014)Cite this article

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Transplantation-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication of allogeneic hematopoietic SCT (HSCT). Particularly, prognosis of the TA-TMA with multiorgan impairment is poor because there is no definitive therapy.1, 2, 3 The pathogenesis of TA-TMA remains undetermined; however, Jodele et al.4 reported that dysregulation of the complement system may be involved in the pathogenesis of TA-TMA. Eculizumab, a humanized moAb against the complement component C5 that prevents tissue damage by blocking the formation of the membrane attack complex, has been successful in the treatment of paroxysmal nocturnal hemoglobinuria or atypical hemolytic uremic syndrome (aHUS).5,6 Thus, if uncontrolled activation of the complement system has an important role in the development of TA-TMA, eculizmab could be a targeted therapy for TA-TMA.

We report the case of a 9-year-old male who was diagnosed with SAA. The patient underwent transplantation with HLA-identical BM cells from the sibling after treatment with fludarabine, CY and antithymocyte globulin (ATG). CsA was administered as a prophylaxis for acute GVHD. Recovery of WBC after HSCT was poor due to mixed chimerism. Next, the patient received DLI twice (on days 22 and 45). On day 54, the patient had acute GVHD (skin: stage 1; gut: stage 1). Despite treatment with methylprednisolone (mPSL) in addition to CsA, gut symptoms (for example, abdominal pain and melena) worsened with protein-losing enteropathy on day 80. Pathological findings of the duodenal mucosal membrane biopsied by intestinal endoscopy were consistent with those for GVHD (stage 4, grade III). Efficacy of administration of 2.5 mg/kg ATG on day 112, infliximab from day 161 or tacrolimus instead of CsA from day 189 was limited for gut GVHD. Therefore, from day 237, the patient received mPSL (1 mg/kg) and infliximab (every 3 weeks) as treatment for GVHD.

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Acknowledgements

We thank Yoko Yoshida, MD (Department of Blood Transfusion, Nara Medical University) for estimating the expression of CFH, CHFR-1, -3 and anti-CFH antibody.

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  1. Department of Pediatrics, Kinki University Faculty of Medicine, Osaka, Japan

    M Okano, N Sakata, S Ueda & T Takemura

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  1. M Okano
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  2. N Sakata
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Correspondence to N Sakata.

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Okano, M., Sakata, N., Ueda, S. et al. Recovery from life-threatening transplantation-associated thrombotic microangiopathy using eculizumab in a patient with very severe aplastic anemia. Bone Marrow Transplant 49, 1116–1118 (2014). https://doi.org/10.1038/bmt.2014.97

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