AbstractAbstract 986In 2011, we described the TEMPI syndrome in three patients, a rare condition characterized by the pentad of (1) Telangiectasias, (2) elevated Erythropoietin and resulting erythrocytosis, (3) Monoclonal gammopathy, (4) Perinephric fluid collections, and (5) Intrapulmonary shunting. Since this publication, two additional living patients have been identified. Of note, all patients carried a diagnosis of unexplained polycythemia for many years to decades prior to the realization that the erythrocytosis was only one part of a more complex syndrome.The underlying pathophysiology of the TEMPI syndrome is unknown. Given that the patients did not exhibit symptoms until their 3rd or 4th decade, we felt that the TEMPI syndrome was more likely to be acquired and less likely to be congenital. We hypothesized that the monoclonal paraprotein may play a role in triggering this very unusual pattern of symptoms. Based on this hypothesis, the patients began empiric treatment with the proteasome inhibitor bortezomib, either alone, or as part of an induction regimen prior to autologous stem cell transplantation.The first patient to receive bortezomib, a 48 year old woman, received 8 cycles of intravenous bortezomib, given in standard fashion. Her telangiectasias, which were concentrated over her lips and torso, disappeared rapidly. Her bilateral perinephric fluid collections disappeared and her serum erythropoietin normalized from a peak of >5000 mIU/ml. By the end of the 8 cycles, her IgG kappa paraprotein became undetectable. Before treatment, she was hypoxic to such a degree that she required a wheelchair and continuous supplemental oxygen. Following treatment, her intrapulmonary shunting resolved, her oxygen saturation normalized, and she has resumed jogging. She remains in a complete remission, now fifteen months after her last dose of bortezomib.The second patient, a 55 year old woman, had undergone surgical fenestration of the renal capsule to allow for drainage of the perinephric fluid into her abdomen. The fluid was produced at such a rate that she required regular paracentesis to remove the resulting ascites. She received 6 cycles of intravenous bortezomib. Her telangiectasias resolved, her serum erythropoietin normalized from a peak of 507 mIU/ml, her paO2 improved, and production of perinephric fluid decreased. However, after four months off treatment, the concentration of her IgG kappa paraprotein began to increase, as did her serum erythropoietin. Furthermore, she has developed pulmonary hypertension, which we suspect may represent a rare paraneoplastic condition seen in some patients with multiple myeloma.The third patient, a 52 year old man, has received ten cycles of intravenous bortezomib. He has tolerated therapy well without side-effects. His serum erythropoietin has decreased from 5500 to 2500 mIU/ml. However, he has not shown the same dramatic reduction in the level of his IgG kappa paraprotein, nor has he shown resolution of his telangiectasias, perinephric fluid, or intrapulmonary shunting.The response of the fourth patient to bortezomib was recently described as a letter to the editor in the New England Journal of Medicine.The fifth patient, a 49 year old woman, was referred for evaluation of unexplained and progressive hypoxia requiring the use of continuous supplemental oxygen. She had been diagnosed at age 34 with polycythemia vera and treated with periodic phlebotomy. Telangiectasias were present on the face, chest, abdomen, and back. Erythropoietin was elevated to >8000 mIU/ml and an IgG-kappa paraprotein was identified. Her cardiovascular shunt fraction was 27%. Given the variable response of the other patients to single-agent bortezomib, she began an induction regimen that included cyoclophosphamide, bortezomib, and dexamethasone (CyBorD) with plans for autologous SCT.The efficacy of treatment with bortezomib, as well as the reversible nature of the symptoms, lends support to the hypothesis that the abnormal plasma cell clone and monoclonal gammopathy are the cause of the TEMPI syndrome. Efforts to identify the antigenic target of the paraprotein are underway, using protein microarray and immunohistochemical techniques.We suspect that more patients with the TEMPI syndrome exist. The constellation of the described pentad should raise the potential of this syndrome. We welcome any reader insights into this unusual condition. Disclosures:Raje:Onyx: Consultancy; Celgene: Consultancy; Millennium: Consultancy; Acetylon: Research Funding; Amgen: Research Funding; Eli-Lilly: Research Funding. Somer:BioPat Holdings, Inc.: Consultancy. Off Label Use: We use bortezomib in the treatment of a newly described syndrome, the TEMPI syndrome.
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Jan 1, 2024
Charles Lefkowitz 
Open Access
