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Supplementary Figures 1-3, Tables 1-2 from Downregulation of Notch Pathway by a γ-Secretase Inhibitor Attenuates AKT/Mammalian Target of Rapamycin Signaling and Glucose Uptake in an ERBB2 Transgenic Breast Cancer Model

Abstract 4528 Background: Atraumatic splenic rupture is a known complication of amyloidosis. We report a female patient with amyloidosis who developed spontaneous splenic rupture in the peri transplant period. Case report: A 56 years old Caucasian woman presented with renal failure (creatinine 1.7 mg/dL) and nephrotic-range proteinuria (3.6 grams in 24 hours). Renal biopsy showed mesangial expansion with increased diffuse infiltrate and Congo red stain positivity consistent with renal amyloidosis. Bone marrow (BM) biopsy showed 5% plasma cells. Pre-transplant CT scan showed hepatosplenomegaly. 13.16 million CD34+ cells/kg of G-CSF mobilized progenitor cells were collected without complications. She received high dose melphalan at 200 mg/m2 followed by autologous hematopoietic cell transplantation (HCT). On post transplant day +8, she developed initial intraperitoneal hemorrhage from spontaneous splenic rupture. The post-transplant course was complicated with tracheal intubation, worsening renal failure requiring hemodialysis, and episodic hypertensive episodes with posterior reversible encephalopathy syndrome, making her a poor candidate for immediate surgical intervention. A day +60 BM biopsy showed normal cellularity with mild megakaryocytic hyperplasia. There was amyloid deposition in 30% of marrow space by Congo red stain. She underwent exploratory laparotomy and splenectomy on day +70 post transplant. Spleen was enlarged, measuring 18 × 15 × 9 cm in size, and weighed 1630 grams. There were multiple areas of hemorrhage and necrosis with multifocal and extensive nodular deposition of pink, amorphous, and waxy material. Congo red stain showed apple-green birefringence in associated collagen and vessel walls. Thioflavin T was strongly positive, confirming the presence of amyloid. No evidence of lymphoproliferative disorder or plasma cell dyscrasia was seen. The patient developed rebleeding and was treated with aminocaproic acid and multiple platelet transfusions. Her post transplant course has been further complicated with the development of autoimmune hemolytic anemia and immune thrombocytopenic purpura, consistent with Evans syndrome. She required treatment with corticosteroids, intravenous immunoglobulin, rituximab and colchicine. More than five months from her transplant, the patient is alive, independent of transfusion support, and in complete remission. Discussion: Splenic involvement in amyloidosis is rather frequent (5-10%). However, an atraumatic rupture of the affected spleen is thought to be an extremely rare event. There have been only 5 published cases of spontaneous splenic rupture in the context of autologous HCT in patients with amyloidosis (Am J Hematol 2003;74:131-135, Eur J Haematol 2008;80:182-184, Wien Klin Wochenschr 2006;118:49-53). One case was associated with G-CSF stem cell mobilization. The range of timing of splenic rupture in reported cases was day +1 to +23 post transplant. The reported spleen weight ranged from 159 to 450 grams. Most patients had elevated white blood cell count at the time of rupture. Although the occurrence of atraumatic splenic rupture in amyloid patients has been described, spontaneous splenic rupture in the context of autologous HCT still remains rare. Transplant physicians should maintain high index of suspicion for spontaneous splenic rupture in amyloid patients and laparoscopic splenectomy can be safely performed in the post-transplant period granted that their cardiac status can tolerate pneumoperitoneum. Disclosures: No relevant conflicts of interest to declare.