Idiopathic multicentric Castleman disease (iMCD)-idiopathic plasmacytic lymphadenopathy: A distinct subtype of iMCD-not otherwise specified with different clinical features and better survival.

Idiopathic multicentric Castleman disease (iMCD) is subclassified into iMCD-thrombocytopenia, anasarca, reticulin fibrosis, renal dysfunction, organomegaly (TAFRO) and iMCD-not otherwise specified (NOS) according to the Castleman Disease Collaborative Network (CDCN) consensus criteria. With a deeper understanding of iMCD, a group of patients with iMCD-NOS characterised by polyclonal hypergammaglobulinaemia, plasmacytic/mixed-type lymph node histopathology and thrombocytosis has attracted attention. This group of patients has been previously described as having idiopathic plasmacytic lymphadenopathy (IPL). Whether these patients should be excluded from the current classification system lacks sufficient evidence. This retrospective analysis of 228 patients with iMCD-NOS identified 103 (45.2%) patients with iMCD-IPL. The clinical features and outcomes of patients with iMCD-IPL and iMCD-NOS without IPL were compared. Patients with iMCD-IPL showed a significantly higher inflammatory state but longer overall survival. No significant difference in overall survival was observed between severe and non-severe patients in the iMCD-IPL group according to the CDCN severity classification. Compared with lymphoma-like treatments, multiple myeloma-like and IL-6-blocking treatment approaches in the iMCD-IPL group resulted in significantly higher response rates and longer time to the next treatment. These findings highlight the particularities of iMCD-IPL and suggest that it should be considered a new subtype of iMCD-NOS.

Sirolimus is effective for refractory/relapsed idiopathic multicentric Castleman disease: A single-center, retrospective study.

Refractory/relapsed idiopathic multicentric Castleman disease (R/R iMCD) has limited treatment options. With studies showing increased mTOR activation in iMCD patients, sirolimus becomes an attractive and promising therapy for R/R iMCD. Here we report the results of a retrospective study involving 26 R/R iMCD patients treated with sirolimus-containing regimen. The median age at sirolimus initiation was 40.5 years (23-60), with a median prior treatment line of 2 (1-5). 18 patients (69.2%) achieved symptomatic and biochemical response, with a median time to at least overall partial remission of 1.9 months (0.5-14.6). The median follow-up time from sirolimus initiation was 11.7 months (1.6-50.7) and the median time to next treatment (TTNT) was 46.2 months. No patients died at the end of follow-up. Most of the patients in the cohort are in ongoing responses and continue sirolimus therapy. Sirolimus is well tolerated with minor adverse effects. In conclusion, sirolimus is effective for R/R iMCD patients with good tolerance.

Diagnostic Utility of Interferon-Gamma Release Assay in Tuberculous Lymphadenitis.

Objective The aim of this study was to evaluate the diagnostic performance of T-SPOT.TB for tuberculous lymphadenitis. Methods Suspected tuberculous lymphadenitis patients between September 2010 and September 2018 who had both peripheral blood T-SPOT.TB test and lymph node biopsy were retrospectively enrolled in this study. The cutoff value of T-SPOT.TB test for peripheral blood was set as 24 spot forming cell (SFC)/10 6 periphreral blood monocyte cell (PBMC) according to the instruction of testing kits. The gold standard for diagnosis of TBL was the combination of microbiology results, histopathology results and patient's response to anti-TB treatment. Diagnostic efficacy of T-SPOT.TB was evaluated, including sensitivity, specificity, accuracy, predictive values, and likelihood ratio. Results Among 91 patients who met the inclusion criteria, we excluded 8 cases with incomplete clinical information and 6 cases who lost to follow-up. According to the gold standard, there were 37 cases of true TBL (9 confirmed TBL and 28 probable TBL), 30 cases of non-TBL, and 10 cases of clinically indeterminate diagnosis who were excluded from the final analyses. The T-SPOT.TB tests yielded 43 cases of positive response and 24 cases of negative response. The sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of peripheral blood T-SPOT.TB for diagnosing TBL were 89.2%, 66.7%, 79.1%, 76.7%, 83.3%, 2.68 and 0.16, respectively. The number of SFCs of T-SPOT.TB in TBL patients [432(134-1264)/10 6 PBMCs] was higher than that in non-TBL patients [0 (0-30) /10 6PBMCs] with a significant difference (Z=-5.306, P <0.001).Conclusion T-SPOT.TB is a rapid and simple diagnostic test for TBL with a high sensitivity and negative predictive value.

A prospective study of zanubrutinib, a Bruton tyrosine kinase inhibitor, in relapsed/refractory idiopathic multicentric Castleman disease.

Relapsed and refractory (R/R) idiopathic multicentric Castleman disease (iMCD) is a clinical challenge with no standard treatment. In this preliminary clinical trial, we investigated the efficacy and safety profiles of a Bruton tyrosine kinase inhibitor (BTKi), zanubrutinib, in patients with R/R iMCD. The primary endpoint was the overall response rate at Week 12 according to the Castleman Disease Collaborative Network (CDCN) response criteria. The trial was terminated early due to a lack of treatment response in the first enrolled 5 patients. Although 3 patients achieved symptomatic response, none of the 5 patients had an overall response by Week 12. One patient had progressive disease and the other 4 had stable disease. The study drug was well tolerated without grade 2 or higher adverse events. Our findings suggest that BTKi therapy is not effective for iMCD, and further attempts at single-agent therapy with zanubrutinib or other BTKis for iMCD should be considered with caution and probably avoided. This trial was registered at www.clinialtrials.gov as #NCT04743687.

A prospective, multicenter study of bortezomib, cyclophosphamide, and dexamethasone in relapsed/refractory iMCD.

Relapsed and refractory (R/R) idiopathic Multicentric Castleman disease (iMCD) is a clinical challenge with few treatment options. In this first multicenter, prospective trial which implemented the recently published CDCN response criteria, we evaluated the efficacy and safety profiles of bortezomib-cyclophosphamide-dexamethasone (BCD) regimen in 24 R/R iMCD patients. By 6 months, 15 patients (62.5%) achieved overall treatment responses; four patients (16.7%) had stable disease and five patients (20.8%) suffered from progression of disease. Even when considering all patients, there were significant (p < .05) improvements in median symptom score, hemoglobin, platelet count, C-reactive protein (CRP) erythrocyte sedimentation rate (ESR), IL-6, albumin, and immunoglobin G (IgG) after treatment. The regimen was well tolerated without grade 3 or higher adverse events. Estimated 1-year progression-free survival (PFS) and overall survival (OS) were 79% and 92%, respectively. BCD regimen is an effective and safe treatment option for R/R iMCD patients. This trial was registered at www.chictr.org.cn as # ChiCTR1800019342.

UCD with MCD-like inflammatory state: surgical excision is highly effective.

Unicentric Castleman disease (UCD) is a rare lymphoproliferative disorder presenting as a single nodal mass with characteristic histopathology. Patients with UCD are typically asymptomatic with normal laboratory markers, whereas patients with multicentric Castleman disease (MCD) demonstrate multicentric lymphadenopathy and cytokine storm-induced systemic inflammatory symptoms. This retrospective analysis of 116 UCD cases identified 19 (16.4%) cases with an MCD-like inflammatory state (UCD-MIS). We compared treatments and outcomes between cases of UCD-MIS and UCD-non-MIS to evaluate the role of surgery and illuminate biological behavior of UCD-MIS. There were differences in the distribution of histopathological subtypes (plasmacytic histopathology was more frequently seen, 52.6% vs 13.4%; P < .001) between the 2 groups. However, both groups demonstrated good responses to surgical treatment, suggesting that UCD-MIS in some patients still shared common biological behavior with UCD in other patients. Sixteen (94.2%) patients with UCD-MIS underwent complete surgical excision alone, and the systemic inflammation resolved completely in all of them. This high response rate suggests surgical treatment as a potential cure for this unique subset of patients. After a median follow-up duration of 64 months (range, 2-239 months), neither lymphadenopathy nor the inflammatory state recurred. However, inflammation may progress in patients with irresectable disease, and treatment options other than surgery should be considered in these patients.