Vitamin A deficiency in the absence of organic gastrointestinal abnormalities is exceedingly rare in the developed world. A strong index of suspicion and thorough review of systems are invaluable in evaluating patients with unexplained corneal melt.
immune effector cells and evade the immune response. Nivolumab is a member of the new class of immunotherapies, so called "checkpoint" inhibitors, with tremendous activity in solid tumours as well as Hodgkins lymphoma. 1 Case Report: Here we describe the outcome of a 25 yo woman diagnosed with Hodgkin's lymphoma (HL, classical nodular) in 2009 after presenting with neck lymphadenopathy. She was treated but relapsed in October of 2010 and received salvage chemotherapy followed by autologous stem cell transplantation. In November 2011, she relapsed again and achieved partial remission after multiple rounds of therapies including brentuximab vedotin. In October 2013, she underwent an allogeneic stem cell transplant (ASCT) with fludarabine and busulfan conditioning from a matched unrelated donor. Her transplant course was complicated by mild chronic GVHD presenting as nausea, vomiting and joint pains. She also developed an atypical "chronic" GVHD manifested as intermittent hemibody sensory loss, tingling, and weakness with periodic confusions which could only be controlled by low dose daily prednisone. At day+590 post ASCT, she relapsed classical nodular sclerosing HL. At a second institution, she began Nivolumab at 3mg/Kg intravenously. Fourteen days after her first dose, she developed grade III transaminitis and was placed on prednisone 2mg/kg for 7 day but 24 days after the Nivolumab dose, she presented to our ER with RUQ abdominal pain, pruritis, jaundice and grade IV transaminitis with bilirubin of 10 which subsequently peaked to 31 (Figure 1). A workup for infectious etiology (EBV, hepatitis, CMV, Adenovirus and HHV6) was negative. An abdominal ultrasound was negative for VOD/SOS. A liver biopsy was consistent with aGVHD as evidenced by loss of interlobular bile ducts, mild centrilobular perivenular fibrosis, increased intrasinusoidal kupffer cells, and hepatocyte injury (Figure 2). She also developed severe low TSH/free T4 levels suggestive of central hypothyroidism. She was restarted on steroids at 2mg/kg but after 2 weeks, developed hepatorenal syndrome and hypotension. Hemodislysis/Plasmaphoresis followed by extracorporeal photophoresis was initiated but unfortunately her condition rapidly deteriorated. She ultimately succumbed to hypotension with disseminated intravascular coagulation and multi-organ failure. Conclusion: To our knowledge this is the first case of documented acute GVHD induced by an anti-PD1 antibody following ASCT. The use of immune checkpoint inhibitors after ASCT should be examined carefully.
61 Background: Early results from recent studies using immune checkpoint blockade targeting programmed death 1 (PD-1) have suggested that pleomorphic undifferentiated sarcomas may have response rates of over 40%. As of now predictive biomarkers for response and resistance have been incompletely characterized. Methods: A 58-year-old man who received radiation for a head and neck squamous cell cancer, developed a radiation-induced undifferentiated pleomorphic sarcoma (UPS) in his neck in 2014. His sarcoma was resected but recurred in 2015. He received adjuvant radiation after surgical debulking in September 2015 and was found on radiation simulation scan to have new widespread metastatic disease involving liver, lung, and bone. He started treatment on nivolumab in November 2015 and has had a sustained near complete response in all lesions. Results: All sites had a near complete response to nivolumab treatment. Pre treatment tissue analysis revealed no mutations or amplifications in 134 cancer-related genes, on the Oncomine Assay (Life Technologies, Inc.). Normal tissue was noted to be heterozygous for BRCA2 N372H, while the allelic fraction of the 372H variant in the tumor was found to be 85%. Programmed death ligand-1 (PDL-1) immunohistochemistry staining of the tumor tissue was negative. Tumor infiltrating lymphocytes were not noted in the tumor tissue specimen. Conclusions: This patient exhibited a near complete response to all sites of disease, with remaining PET avidity in a single hilar node. The role of the BRCA2 variant and radiation just prior to starting nivolumab is unknown. BRCA2 N372H is a common single nucleotide polymorphism (SNP) in the population with a minor allele frequency of 0.25. Although the effect of the 372H variant on BRCA2 protein structure is predicted to be minimal, population studies have suggested a slightly increased risk of breast and ovarian cancer in homozygotes. It is possible that the radiation treatment to the site of recurrence in the head and neck, resulted in an abscopal effect enhancing the therapeutic effect of nivolumab therapy. Additional testing on his tissue is being done to further investigate the response.
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