Thalidomide for tocilizumab‐resistant ascites with TAFRO syndrome

Tatekawa, Shotaro; Umemura, Koji; Fukuyama, Ryuichi; Kohno, Akio; Taniwaki, Masafumi; Kuroda, Junya; Morishita, Yoshihisa

doi:10.1002/ccr3.284

Cited by 37 publications

(28 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 month after the administration of cyclosporin A (4 mg/kg /day) on day 51, the platelet count had increased to the normal range and the patient's ascites and pleural effusion had completely resolved. Furthermore, Tatekawa et al reported a 56-yearold man who had TAFRO syndrome [18]. Combined administration of tocilizumab and prednisolone improved lymphadenopathy, pleural effusion, anemia, thrombocytopenia, and hypoalbuminemia, but elevation of C-reactive protein Fig.…”

Section: Discussionmentioning

confidence: 97%

TAFRO syndrome with refractory thrombocytopenia responding to tocilizumab and romiplostim: a case report

et al. 2018

View full text Add to dashboard Cite

Thrombocytopenia, anasarca, fever, reticulin fibrosis, organomegaly (TAFRO) syndrome is a unique clinicopathologic subtype of multicentric Castleman's disease that has recently been identified in Japan. However, little is known about its renal histological changes and the optimal treatment for TAFRO syndrome. An 80-year-old Japanese woman was admitted to our hospital for evaluation of severe anasarca and weight gain (10 kg in a month). She had polyneuropathy, monoclonal plasma cell proliferative disorder with positive kappa M-protein, a sclerotic bone lesion, elevation of vascular endothelial growth factor (VEGF), skin changes, and extravascular volume overload, which fulfilled the diagnostic criteria for POEMS (polyneuropathy, organomegaly, endocrinopathy, and monoclonal protein, skin changes) syndrome. However, kappa-type M-protein and thrombocytopenia with positivity of platelet-associated immunoglobulin G antibody were unusual, and fitted the diagnostic criteria for TAFRO syndrome. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis with endothelial swelling and the infiltration of monocytes and neutrophils without specific immunoglobulin deposits. Her systemic symptoms were refractory to initial treatment with high-dose melphalan and glucocorticoids. Alternative therapy with an anti-interleukin-6 (IL-6) receptor antibody (tocilizumab) effectively controlled the symptoms, while a thrombopoietin receptor agonist (romiplostim) was effective for her thrombocytopenia. Results suggest that IL-6-VEGF axis and an autoimmune mechanism may be responsible for TAFRO syndrome with clinical features of POEMS and refractory thrombocytopenia, which can be successfully treated with combination of tocilizumab and romiplostim.

show abstract

Section: Discussionmentioning

confidence: 97%

TAFRO syndrome with refractory thrombocytopenia responding to tocilizumab and romiplostim: a case report

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Both iMCD‐TAFRO patients were anti‐IL‐6 nonresponders and all three iMCD‐NOS patients treated with anti‐IL‐6‐therapy responded. Importantly, there have been reports of iMCD‐TAFRO cases that have responded to anti‐IL‐6‐therapy and others that have not . The proteomic differences between the two groups may represent differences between clinical subtypes or be a signature of anti‐IL‐6 response.…”

Section: Discussionmentioning

confidence: 99%

Plasma proteomics identifies a ‘chemokine storm’ in idiopathic multicentric Castleman disease

et al. 2018

View full text Add to dashboard Cite

Human Herpesvirus-8 (HHV-8)-negative/idiopathic multicentric Castleman disease (iMCD) is a poorly understood disease involving polyclonal lymphoproliferation with dysmorphic germinal centers, constitutional symptoms, and multi-organ failure. Patients can experience thrombocytopenia, anasarca, reticulin fibrosis, renal dysfunction, organomegaly, and normal immunoglobulin levels, - iMCD-TAFRO. Others experience thrombocytosis, milder effusions, and hypergammaglobulinemia, -iMCD-Not Otherwise Specified (iMCD-NOS). Though the etiology is unknown in both subtypes, iMCD symptoms and disease progression are believed to be driven by a cytokine storm, often including interleukin-6 (IL-6). However, approximately two-thirds of patients do not respond to anti-IL-6 therapy; alternative drivers and signaling pathways are not known for anti-IL-6 nonresponders. To identify potential mediators of iMCD pathogenesis, we quantified 1129 proteins in 13 plasma samples from six iMCD patients during flare and remission. The acute phase reactant NPS-PLA2 was the only significantly increased protein (P = .017); chemokines and complement were significantly enriched pathways. Chemokines represented the greatest proportion of upregulated cytokines, suggesting that iMCD involves a chemokine storm. The chemokine CXCL13, which is essential in homing B cells to germinal centers, was the most upregulated cytokine across all patients (log2 fold-change = 3.22). Expression of CXCL13 was also significantly increased in iMCD lymph node germinal centers compared to controls in a stromal meshwork pattern. We observed distinct proteomic profiles between the two iMCD-TAFRO patients, who both failed anti-IL-6-therapy, and the four iMCD-NOS patients, in whom all three treated with anti-IL-6-therapy responded, suggesting that differing mechanisms may exist. This study reveals proteomic differences between flare and remission and the potential to molecularly define iMCD subgroups.

show abstract

“…A 12-year-old Japanese male was referred to us with pitting edema of lower limbs and high fever refractory to antibiotics for Some TAFRO syndrome cases refractory to tocilizumab have been reported, [6][7][8][9] but the timing of evaluating the efficacy of tocilizumab was too early. In randomized double-blind placebo-controlled trials of siltuximab for iMCD, a median time of 33 days was required to show a response to siltuximab in responders.…”

Section: A Pediatric Case Of Tocilizumab-resistant Tafro Syndrome Trementioning

confidence: 99%

A pediatric case of tocilizumab‐resistant TAFRO syndrome treated successfully with rituximab

Minamikawa

Matsumura

Sato

et al. 2020

Pediatric Blood & Cancer

View full text Add to dashboard Cite

Thalidomide for tocilizumab‐resistant ascites with TAFRO syndrome

Cited by 37 publications

References 30 publications

TAFRO syndrome with refractory thrombocytopenia responding to tocilizumab and romiplostim: a case report

TAFRO syndrome with refractory thrombocytopenia responding to tocilizumab and romiplostim: a case report

Plasma proteomics identifies a ‘chemokine storm’ in idiopathic multicentric Castleman disease

A pediatric case of tocilizumab‐resistant TAFRO syndrome treated successfully with rituximab

Contact Info

Product

Resources

About