S5575 A Case of Decompensated Cirrhosis Secondary to Sickle Cell Hepatopathy (SCH) Managed With Orthotopic Liver Transplantation (OLT) Followed by Haploidentical Hematopoietic Stem Cell Transplantation (HSCT)

Introduction: Cirrhotic patients due to SCH often face poor outcomes with liver transplantation alone due to concern of recurrent hepatic graft damage. We present a unique case of OLT followed by haploidentical HSCT in a 26-year-old man with severe sickle cell disease (SCD) complicated by cirrhosis. Case Description/Methods: A 26-year-old man with HbSS SCD complicated by recurrent vaso-occlusive crises and avascular hip necrosis developed decompensated cirrhosis from SCH. Despite treatment of SCD with transfusions and hydroxyurea, his cirrhosis progressed with refractory ascites, spontaneous bacterial peritonitis, and hepatic encephalopathy. With a MELD score of 36, he underwent successful OLT with the institution's immunosuppression protocol of basiliximab induction, steroid taper, mycophenolate modafinil and maintenance tacrolimus. His post-transplant course was relatively uncomplicated with just biliary anastomotic stricture managed with endoscopic stenting. Seven months post-OLT, the patient underwent HSCT with Flu/Cy/ATG/TBI conditioning. Tacrolimus was held during the conditioning. Complications included cutaneous reaction to ampicillin requiring intravenous methylprednisolone and ruxolitinib due to initial concern for early graft vs host disease (GVHD) which was later felt less likely based on timing and presentation characteristics. Sirolimus, used for immunosuppression/GVHD prophylaxis, was switched to tacrolimus due to possible cutaneous adverse reaction and was continued to prevent OLT rejection. Full donor engraftment was observed at day 60. Hemoglobin electrophoresis was consistent with donor phenotype. Over 18 months post-OLT and 12 months post-HSCT, the patient continues to thrive with significant improvement in functional status and physical health. Discussion: This case demonstrates a novel approach of sequential liver transplantation followed by haploidentical HSCT in a patient with severe SCD complicated by decompensated cirrhosis secondary to SCH. To our knowledge, this is the first reported case of planned sequential transplantation for SCD-related cirrhosis in the United States. Patients with SCD who have undergone liver transplantation can have significant risk of graft loss, with studies showing up to 22% requiring re-transplantation due to SCD complications. Our approach addresses both the end-organ damage and the underlying disease, providing a potentially curative option for patients who would normally be declined for liver transplantation.