Renal and Neurological Response with Eculizumab in a Patient with Transplant Associated Thrombotic Microangiopathy after Allogeneic Hematopoietic Progenitor Cell Transplantation

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.

Is complement blockade an acceptable therapeutic strategy for hematopoietic cell transplant-associated thrombotic microangiopathy?

“…Three different case reports describe three patients responding to the use of eculizumab, although two of them died after initial response. [53][54][55] The causes of death were acute respiratory distress syndrome of unknown cause 53 and diffuse alveolar hemorrhage. 55 Larger prospective trials are needed to confirm the value of eculizumab in TA-TMA.…”

“…[53][54][55] The causes of death were acute respiratory distress syndrome of unknown cause 53 and diffuse alveolar hemorrhage. 55 Larger prospective trials are needed to confirm the value of eculizumab in TA-TMA. At the present time, eculizumab-use may result in a hematologic response in TA-TMA; however, the efficacy may be less in sick patients with severe manifestations and other comorbidities, and hematologic response does not guarantee survival.…”

Severe, persistent neurotoxicity after transplant‐associated thrombotic microangiopathy in a pediatric patient despite treatment with eculizumab

“…14 In addition to improving overall survival, improvement and resolution of acute neurologic toxicities after eculizumab therapy is repeatedly reported. 15,16 For optimal effect in TA-TMA, eculizumab is dosed weekly for 4 weeks, and thereafter dosed to maintain a CH50 level of 0-3 CAE for an additional two weeks, and then stopped. 13…”

“…In a pediatric cohort with high‐risk TA‐TMA, defined as proteinuria >30 mg/dL and evidence of complement system activation (elevated s5b‐9) 1‐year overall survival after treatment with eculizumab was 56% compared to 9% for untreated patients ( P = 0.003) . In addition to improving overall survival, improvement and resolution of acute neurologic toxicities after eculizumab therapy is repeatedly reported . For optimal effect in TA‐TMA, eculizumab is dosed weekly for 4 weeks, and thereafter dosed to maintain a CH50 level of 0‐3 CAE for an additional two weeks, and then stopped …”

Eculizumab for transplant‐associated thrombotic microangiopathy in adult allogeneic stem cell transplant recipients

“…25,35,36 A growing body of literature supporting this claim is accumulating with the publication of a number of case reports and case series documenting positive treatment responses. 1,2,13,16,30,[36][37][38][39][40][41][42][43] However, a majority of these reports are in pediatric patients and there remains a paucity of data. Recognizing this, the ASH/EBMT joint study group published a 2014 review which stressed that the research agenda should no longer focus on large clinical trials to address the scarcity of data, but emphasized that any study-whether randomized or observational-is strongly encouraged.…”