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Transplant- Associated Thrombotic Microangiopathy in a Beta-Thalassemia Major Patient Following Bone Marrow Transplant- Case Report
Transplant-associated thrombotic microangiopathy (TA-TMA) is a significant complication of hematopoietic stem cell transplantation and poses a challenge with diagnosis and management.
Objectives:
To report a case of TA-TMA in an allogeneic bone marrow transplant (BMT) patient and discuss diagnostic and management challenges.
Design/Method:
Case Report.
Results:
Seven year old female with B-thalassemia major who underwent 10/10 matched unrelated donor BMT. Her conditioning regimen included Busulfan, Fludarabine, Cyclophosphamide and ATG, graft versus host disease (GVHD) prophylaxis included cyclosporin and short course methotrexate. Post-transplant course was complicated by grade II acute GVHD, intracranial bleed, GI hemorrhage and pericardial effusion. She developed several episodes of acute kidney injury post-transplant with recovery of renal function back to baseline creatinine (0.3-0.5 mg/dL). Six months post transplant the patient developed hematuria and worsening proteinuria followed by intractable hypertension. Renal function gradually worsened with creatinine rising to ~1.6 mg/dL and ended up with oliguria and fluid overload. In addition she developed hemolytic anemia, thrombocytopenia and peripheral blood schistocytes. Several measures were attempted to improve her renal function including stopping her calcineurin inhibitor, decreasing her diuretic regimen and stopping ACE inhibition. Renal biopsy was obtained and showed acute, severe thrombotic microangiopathy. Complement serologies (C3, C4, CFI, CFH levels and CFH autoantibody) were all normal or elevated. Hemodialysis, therapeutic plasma exchange and basiliximab were initiated. She received 2 doses of basiliximab and 10 treatments of plasma exchange, resulting in no response. The patient continued on thrice weekly dialysis. The patient tolerated dialysis with great difficulty complicated by bilateral eye pain, dizziness, extremity tingling and abdominal pain during her treatments. Finally the patient developed a syncopal event with mental status changes following one of her dialysis episodes. EEG confirmed seizure activity. Brain MRI showed diffuse white matter abnormality consistent with severe TMA. Given the patient’s progressive worsening and extreme symptoms, Eculizumab was started. After 3 doses, she has begun to show signs of hematologic recovery with no signs of renal recovery. Her blood pressure remains very difficult to control.
Conclusion:
TA-TMA is an uncommon but significant complication of HSCT that presents significant diagnostic and management challenges. Even with accurate diagnosis (clinically and histologically), optimal treatment strategies remain elusive and the prognosis is poor.