Small vessels, big trouble in the kidneys and beyond: Hematopoietic stem cell transplantation-associated thrombotic microangiopathy

Divisions of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Blood (Impact Factor: 10.43). 05/2011; 118(6):1452-62. DOI: 10.1182/blood-2011-02-321315
Source: PubMed

ABSTRACT Transplantation-associated thrombotic microangiopathy (TA-TMA) is a challenging diagnosis after hematopoietic stem cell transplantation. Although endothelial injury represents the final common pathway of disease, the exact pathophysiology of TA-TMA remains unclear. Potential causes include infections, chemotherapy, radiation, and calcineurin inhibitors. Recent literature addresses the roles of cytokines, graft-versus-host disease, the coagulation cascade, and complement in the pathogenesis of TA-TMA. Current diagnostic criteria are unsatisfactory, because patients who have received a transplant can have multiple other reasons for the laboratory abnormalities currently used to diagnose TA-TMA. Moreover, our lack of understanding of the exact mechanism of disease limits the development and evaluation of potential treatments. Short- and long-term renal complications contribute to TA-TMA's overall poor prognosis. In light of these challenges, future research must validate novel markers of disease to aid in early diagnosis, guide current and future treatments, prevent long-term morbidity, and improve outcomes. We focus on TA-TMA as a distinct complication of hematopoietic stem cell transplantation, emphasizing the central role of the kidney in this disease.

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    • "Transplantation-associated thrombotic microangiopathy (TA-TMA) represents a challenge after allogeneic hematopoietic progenitor cell transplantation because of diagnostic uncertainties, lack of established treatment, and an overall poor prognosis [1]. Eculizumab, which is a monoclonal antibody against terminal complement, has been used successfully in atypical hemolytic and uremic syndrome and TA-TMA associated with solid organ transplantation. "
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    ABSTRACT: Transplantation-associated thrombotic microangiopathy (TA-TMA) is a challenge after allogeneic hematopoietic progenitor cell transplantation, considering the diagnostic uncertainties and lack of established treatment. We report a 43-year-old male patient who was diagnosed as TA-TMA after allogeneic progenitor cell transplantation for a progressive ALK negative anaplastic large cell lymphoma and responded to eculizumab with dramatically improving neurological status and renal function. Rapid neurological and renal recovery achieved after eculizumab could support a possible relationship between complement activation and TA-TMA. Eculizumab should be a reasonable treatment approach in patients with TA-TMA after allogeneic hematopoietic progenitor cell transplantation.
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