Abstract: SA-PO960

Transplant Associated Thrombotic Microangiopathy (TA-TMA) in a Child with Neuroblastoma and Complement Factor Deletion: A Novel Association

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports

Authors

  • Chinnadurai, Amirtha, Yale University School of Medicine, New Haven, Connecticut, United States
  • Suliman, Ali Y, Yale univeristy School of medicine, Hamden, Connecticut, United States
  • Kent, Michael, Yale University, New Haven, Connecticut, United States
  • Tufro, Alda, Yale University School of Medicine, New Haven, Connecticut, United States
Background

TA-TMA is an increasingly recognized morbidity following stem cell transplantation. It is uncommon in autologous stem cell transplantation (auto-SCT). Risk factors for TA-TMA following auto-SCT include specific malignancies such as neuroblastoma, platinum based chemotherapy, total body irradiation and infections. To our knowledge, there are no previous reports of genetic predisposition as a cause of TMA in neuroblastoma following auto-SCT.

Methods

A 3-year-old hispanic boy with stage IV poorly differentiated neuroblastoma, received 6 cycles of high dose chemotherapy, primary tumor resection and underwent auto-SCT two months later. His post-stem cell transplant course was complicated with septic shock with multi-organ dysfunction including respiratory failure, recurrent supraventricular tachycardia and acute kidney failure requiring continuous renal replacement therapy, which subsequently resolved and the neuroblastoma remained in remission. Two months after auto-SCT, he developed refractory hypertension on multiple anti-hypertensive therapy, seizures associated to acute posterior reversible leukoencephalopathy syndrome, recurrent acute kidney injury and severe thrombocytopenia and anemia, dependent on daily transfusions. The diagnosis of TMA was then established with the presence of schistocytes, low serum haptoglobulin, elevated lactate dehydrogenase, negative Coombs, normal ADAMTS13, marked decrease in CH50 and complement component 5 activity. Complement gene panel revealed homozygous deletion of CFHR1 gene. He received weekly eculizumab for two months leading to normalized renal function, eGFR of more than 100ml/min/1.73m2 (modified schwartz), resolved hypertension, proteinuria, anemia and thrombocytopenia. Eculizumab therapy was tapered as all TMA signs resolved, and remains in remission to date (23 months from onset) ,while receiving Eculizumab every two months.

Conclusion

We report for the first time a case of TMA in a child with neuroblastoma harboring a complement genetic mutation known to cause TMA or atypical hemolytic uremic syndrome. It resolved upon Eculizumab and remains in remission after extending the therapy interval to 8 weeks. We hypothesize that complement genetic variants may constitute a risk factor for sporadic TA-TMA.