AUTOINFLAMMATORY DISEASES IN HEMATOLOGY FROM DIAGNOSIS TO TREATMENT

AUTOINFLAMMATORY_DISEASES_IN_HEMATOLOGY_FROM_DIAGNOSIS_TO_TREATMENTkapak

TEMPI SYNDROME

Ünal Ataş

Alanya Alaaddin Keykubat University, Faculty of Medicine, Department of Hematology, Antalya, Türkiye

Ataş Ü. TEMPI Syndrome. In: Kurt Yüksel M, editor. Autoinflammatory Diseases in Hematology from Diagnosis to Treatment. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.133-149.

ABSTRACT

TEMPI syndrome (telangiectasia, high erythropoietin erythrocytosis, monoclonal gammopathy, perinephric fluid collection and intrapulmonary shunt), classified as “plasma cell neoplasms with associated paraneoplastic syndrome”, was first described in 2011. After the description, approximately 44 cases, all of which were case or case series presentations, were added to the literature. The initial findings are usually telangiectasia and polycythemia, and most cases are followed up in different clinics for a long time with these clinical findings or with monoclonal gammopathy of unknown clinical significance without being diagnosed. While patients are often misdiagnosed as having polycythemia vera, patients with TEMPI syndrome have polycythemia accompanied by very high erythropoietin (EPO) levels. In addition, JAK2 gene mutation and features characteristic of myeloproliferative disorders in the bone marrow are not expected. Monoclonal gammopathy involving IgG and IgA type heavy chains has been reported in all cases, except for IgM in 2 cases. Bone marrow clonal plasma cell ratio is expected to be less than 10%. However, some patients have been shown to have smoldering multiple myeloma (MM), symptomatic MM criteria, and lymphoplasmacytic lymphoma in those with additional IgM type monoclonal gammopathy. Perinephric effusion and intrapulmonary shunts are the other two most common clinical findings, although they are not seen in some patients. In addition to these descriptive findings, rare additional clinical conditions, most commonly venous thrombosis, have been reported. It is unknown how clonal plasma cells and/or monoclonal gammopathy trigger the signs and symptoms of TEMPI syndrome. While no clear and single genetic factor or pathway has been identified in etiopathogenesis, there are findings and theories on a case-by-case basis. For diagnosis, telangiectasia, erythrocytosis with high erythropoietin, and monoclonal gammopathy were identified as major; perinephric fluid collection and intrapulmonary shunt were identified as minor; and venous thrombosis were identified as other criteria. In the differential diagnosis, POEMS and TAFRO syndromes and other acquired and congenital causes of erythrocytosis that may occur with high EPO are important. Good responses have been reported to plasma cell targeting agents such as bortezomib, lenalidomide and daratumumab. Despite these agents, there are also relapsed/refractory patients. In some cases, experiences with autologous stem cell transplantation performed for consolidative purposes or due to refractoriness have also been reported. However, there are comments that the combination of daratumumab with bortezomib, lenalidomide or thalidomide may be an effective combination in the treatment of TEMPI syndrome, as a first-line treatment. It is difficult to comment on this issue, as more data need to be collected for the treatment of relapsed and refractory patients. In case of underlying lymphoplasmacytic lymphoma, the combination of rituximab and bortezomib seems to be a suitable option. Although patients may remain undiagnosed for a long time and their response to treatment appears to be good, it is difficult to comment on prognosis because it is a rare entity. For the same reason, there is no clear follow-up plan.

Keywords: Plasma cell neoplasms; TEMPI syndrome; Telangiectasia; Erythrocytosis; Monoclonal gammopathy; Perinephric fluid collection; Intrapulmonary shunt; Paraneoplastic syndrome

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