Management strategies for AIHA include corticosteroids, intravenous immunoglobulin, immunosuppressive agents, cytotoxic agents, monoclonal antibodies (Rituximab) and in severe and or refractory cases splenectomy. Our patient is a 49 year-old Jamaican man with past medical history of HIV infection and recently diagnosed stage IV Hodgkin lymphoma with marrow and organ involvement who presented to the ER with severe fatigue, chills and high-grade fever. CBC testing revealed hemoglobin of 3.2gm/dl with a normal leukocyte and platelet count. Further testing revealed strongly positive direct coombs test, undetectable haptoglobin, elevated unconjugated bilirubin, elevated LDH and plasma free hemoglobin confirming the diagnosis of AIHA. Laboratory parameters for disseminated intravascular coagulation (DIC) were negative. Infection was ruled out with cultures and radiological studies. Severe ongoing hemolysis led to an acute change in mental status, hypotension and acute renal failure requiring the patient to be transferred to the ICU for hemolytic shock. Patient failed to respond to conventional treatments including high dose steroids and IVIG. A single dose of rituximab was also tried without any clinical improvement. Patient’s clinical status deteriorated rapidly and within 48 hours, he developed multi-organ failure requiring continuous venovenous hemodialysis (CVVHD), hemodynamic support with pressors, and aggressive hematological support with multiple blood transfusions. At this point a decision was made to initiate TPE. Within hours of the first TPE, the patient’s clinical status improved. His mental status improved dramatically from a stupor to a fully conscious state. Daily TPE was continued for four days, which resulted in stabilization of his hematocrit, discontinuation of pressors as well as CVVHD. Laboratory parameters of hemolysis normalized. He was eventually able to receive definitive chemotherapy for Hodgkin lymphoma. He is currently three months status post last TPE and undergoing the third cycle of chemotherapy with no recurrence of AIHA. Our experience indicates that TPE can be an effective and rapid treatment modality for patients with severe AIHA secondary to IgG antibodies refractory to conventional means of therapy.

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e18012 Background: Valproic acid (VPA, 2-propylpentanoic acid) is a histone deacetylase inhibitors (HDACi), which has in vitro activity against Acute Myeloid Leukemia (AML) blasts. HDACi produce epigenetic modifications, and may have antineoplastic effects in AML by activating transcriptional silenced genes. The mammalian target of rapamycin (mTOR) pathways constitutive activation has been involved in the pathogenesis of various cancers, including AML. We present a series of two cases of poor risk de novo and refractory elderly AML patients treated with a combination of HDACi VPA and mTOR inhibitor sirolimus (S). Methods: This is a retrospective chart review garnered data on two patients with de novo AML and refractory AML who were treated with a combination therapy of VPA 500 mg three times a day with sirolimus 1 mg by mouth daily. Patients continued to receive treatment until disease progression. Results: Patient 1 achieved transfusion independence and a 6 month CR with ECOG PS 1 without hospitalizations. Repeat BM demonstrated no morphologic or immunophenotypic evidence of AML. Persistent disease was still detectable by FISH. Patient 2 was started on the regimen after persistent disease was detected by day 14 bone marrow, post standard 7 + 3 induction. Repeat bone marrow after 23 days of treatment with VPA and Sirolimus showed no immunophenotypic, morphological or cytogenetic evidence of AML. The patient remained in remission for 9 months on therapy with normal blood counts. Conclusions: We postulate that the use of VPA with sirolimus, is an active combination therapy for elderly, poor risk AML patients who may not otherwise tolerate intensive chemotherapy. The mechanism of action may involve activation of the mTORC2 pathway by HDAC1. Given our observations, further studies are warranted to better define the activity of this or similar combination therapies in elderly AML patients. [Table: see text]

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4382 Recombinant factor VIIa (rVIIa) is currently used for treatment and prevention of bleeding episodes in hemophilia with inhibitors, congenital factor VII deficiency, and acquired hemophilia. We report a series of 3 cases of immune mediated refractoriness to platelet transfusion therapy that were successfully treated with rVIIa, an off-label use. Data was obtained retrospectively over a 6 month period. All patients were known to be platelet refractory with presence of significant titers of plasma HLA antibodies. Two patients had undergone matched unrelated donor HSCT and the third patient suffered from Myelodysplastic syndrome (MDS). Two of the patients presented with GI bleeding and the third with intracranial bleeding. Due to limited availability of HLA matched platelets and negligible increment in platelet count from ABO matched platelets, use of factor VIIa was considered. Transfusion with PRBCs to maintain a Hemoglobin (Hb) > 8.0g/dl and close monitoring of coagulation parameters were performed. Patients received boluses of rFVIIa at 90mcg/kg, every 3–12 hrs. The dose of rFVIIa ranged from 10800–28,000 mcg/day. All three episodes of bleeding achieved clinical or radiologic improvement. No toxicities or arteriothrombotic events were observed with rFVIIa use. Our experience indicates that rFVIIa might be an effective treatment option for patients with refractoriness to platelet transfusion therapy. The optimal dosing schedule in this clinical situation needs to be studied. Patient demographics and outcomes Patient Diagnosis Pre-intervention Hb/platelet rFVIIa used (microgms) PRBC/Platelet transfused (units) Clinical outcome SV – GI bleed ALL-MUD, BMT, day +102. 7.9/4000 28000/d × 4 days 6/3 Bleeding stopped and Hemoglobin stabilized on day 4 CS- GI bleed AML-MUD,BMT, day + 78 7.8/3000 25200/d × 2 days 2/2 Bleeding stopped and Hemoglobin stabilized on day 2 MW-Intracranial hemorrhage MDS – IPSS risk group Intemediate-2 7.6/6000 10800/d × 2 days 2/2 Improvement in Neurological exam and stabilization on CT scan seen by day 3 Disclosures: Off Label Use: Recombinant factor VIIa for refractoriness to platelet transfusion therapy.