Serum Levels Of Soluble Interleukin-2 Receptor Research Articles

Serum Soluble Interleukin-2 Receptor Levels in Hairy Cell Leukemia As a Marker of Tumor Burden with Prognostic Value and As a Tool for Disease Monitoring

Background Neoplastic cells in hairy cell leukemia (HCL) express the α chain of the interleukin-2 receptor on their surface, which is secreted in large amounts in the serum in a soluble form (sIL-2R). High serum levels of sIL-2R have previously been reported in HCL. Thus, we assessed whether serum sIL-2R levels correlated with tumor burden, represented a prognostic factor, and if they could be used as a tool for disease monitoring. Methods Serum levels of sIL-2R were measured in 59 patients affected by classical HCL followed at the Hematology Unit of Padova University Hospital. To assess whether sIL-2R levels were representative of tumor burden, we evaluated the relationship of pre-therapy sIL-2R levels with other hematologic features such as leukocyte count, the presence of splenomegaly, β-2 microglobulin levels, lactate dehydrogenase (LDH) levels, CD38 expression, the percentages of circulating hairy cells and bone marrow infiltration. In 50 patients we investigated whether post-therapy sIL-2R levels correlated with clinical response and measurable residual disease (MRD) status evaluated by immunohistochemistry according to consensus guidelines. To determine the usefulness of serum sIL-2R levels for disease monitoring, yearly serial sIL-2R levels were measured in 59 patients, including 5 (8.4%) cases in watch & wait phase and 54 (91.6%) with disease remission after therapy with purine analogues. sIL-2R kinetics were correlated with time to cytopenia (TTC) (hemoglobin <100g/L, neutrophils < 1000/µL or platelets <100.000/µL) and time to next treatment (TTNT). Serum sIL-2R levels were measured by enzyme-linked immunosorbent assay. The correlation of sIL-2R levels with other variables was evaluated by linear or logistic regression as appropriate. Medians were compared using the Mann-Whitney U test. Survival and univariate analyses for TTC and TTFT were conducted according to the Kaplan-Meier method and Cox proportional hazards model. Results The mean age of patients was 60.6 years; 10 were females (17%), and 49 were males (83%). Among treated patients, 47/54 (87%) received cladribine and 7/54 (13%) pentostatin. Pre-therapy sIL-2R levels significantly correlated with leukocyte count (r 2 = 0.13; p = 0.009), β-2 microglobulin levels (r 2 = 0.44; p < 0.001), CD38 expression (p = 0.018), the percentage of circulating hairy cells (r 2 = 0.17; p = 0.017) and the percentage of bone marrow infiltration (r 2 = 0.15; p = 0.009), but not splenomegaly (p = 0.167) or LDH levels (r 2 = 0.02; p = 0.369). We found a significant difference between serum sIL-2R levels measured before and after therapy (median 16.185 vs 599 kU/L respectively; p < 0.001), with a median reduction in sIL-2R levels of 15.628 kU/L after treatment with purine analogues. A similar decrease in sIL-2R levels after therapy was observed in 4 relapsed patients treated with rituximab-vemurafenib (median pre-therapy sIL-2R 11.460 vs. 467 kU/L after treatment, p = 0.03; median reduction 10.848 kU/L). Among responding patients, the absolute value of log10(sIL-2R) levels measured 6 months after therapy was a predictor of shorter TTNT in univariate analysis (HR 15.14; 95% CI 1.3 - 176; p = 0.03). Furthermore, sIL-2R correlated with the depth of response. Post-therapy median sIL-2R levels were significantly lower in patients achieving a complete remission (CR) versus those who did not (median 568 kU/L for CR vs. 3.272 kU/L for partial remission/stable disease; p = 0.002). A statistically significant difference was also observed in post-therapy sIL-2R levels between MRD- and MRD+ patients (median 502 vs 724 kU/L; p = 0.003) (Figure 1A). In the patients that underwent yearly serial sIL-2R measurements during follow-up, a rise from the nadir after therapy in serum sIL-2R levels of ≥ 25% between two samples was associated with both shorter TTC (HR 26.2; 95 % CI 3.44 - 200; p < 0.001) (Figure 1B) and TTNT (HR 8.83; 95 % CI 1.9 - 40.9; p < 0.001). Conclusion The consistent reduction in sIL-2R levels after therapy and their correlation with other standard disease parameters show how serum sIL-2R levels could be an effective marker of tumor burden in HCL. While more data is required to validate its use in clinical routine, sIL-2R could be used as an effective marker for disease monitoring. Moreover, given the prognostic significance of post-therapy levels, sIL-2R may represent a prognostic factor alongside MRD to identify those patients that are more likely to develop early relapse.

Systematic analysis of liver failure accompanied with hemophagocytic syndrome in adults

Objective: To retrospectively analyze literature reports and summarize the clinical characteristics of liver failure in patients accompanied with adult hemophagocytic syndrome (HPS). Methods: The Wanfang, CNKI, VIP, PubMed, and Ovid databases were searched for relevant literature on liver failure patients accompanied with adult HPS published from January 1980 to May 2022. The final included literature was systematically reviewed after screening. Results: There were a total of 77 liver failure cases accompanied with adult HPS, with an average age of (41.8 ± 12.5) years. The most common clinical manifestations of these cases were persistent high fever, fatigue, gastrointestinal symptoms, and severe jaundice. The imaging changes were not specific, and the most common was hepatosplenomegaly. Laboratory examination showed a significant increase in serum total bilirubin, lactate dehydrogenase, triglycerides, and soluble interleukin-2 receptor levels, as well as serum ferritin, while there was a decrease in prothrombin activity, natural killer cell activity, and hemocytopenia of two or more lineages in peripheral blood. Myelogram examination showed hemophagocytosis. Adult HPS secondary to infection was more likely to be accompanied with liver failure (55.8%), with an overall case fatality rate of 84.4%. Conclusion: Patients with liver failure accompanied with adult HPS have an extremely high mortality rate and a poor prognosis. Early diagnosis and treatment are the keys to improving the prognosis.

Increased serum soluble interleukin-2 receptor levels in dermatomyositis are associated with Th17/Treg immune imbalance.

Dermatomyositis (DM) represents a multifaceted chronic inflammatory myopathy, primarily manifesting as progressive deterioration of muscular and cutaneous tissues. Despite an incomplete comprehension of DM's etiology and pathogenesis, current evidence implicates the involvement of T lymphocyte infiltration, extensive cytokine release, myositis-specific antibodies, and myositis-associated antibodies in disease development. Serum soluble interleukin-2 receptor (sIL-2R) frequently serves as a marker for T cell activation; however, its role remains elusive. Consequently, this investigation sought to elucidate the association between sIL-2R levels, peripheral blood lymphocyte subset counts, and related cytokines in DM patients, with the aim of uncovering the intricate mechanisms underlying DM and establishing a theoretical foundation for the implementation of precise, targeted, individualized immunomodulatory therapy. In this study, a cohort of 60 dermatomyositis (DM) patients, comprising 32 with inactive DM and 28 with active DM, was enrolled and stratified into inactive and active groups based on the Myositis Disease Activity Visual Analogue Scale (MYOACT). Flow cytometry was employed to quantify the absolute counts of peripheral lymphocyte subsets and CD4+T cell subsets in each group, while a flow cytometry bead array was utilized to measure serum cytokine levels. In a comparative analysis between healthy individuals and patients diagnosed with DM, we observed a marked elevation in serum sIL-2R concentrations (P < 0.001) and T-helper 17 cell/regulatory T cell (Th17/Treg) ratios (P < 0.01) within the latter group. A positive correlation was identified between serum sIL-2R levels and various parameters, including ESR, CRP, VAS, AST, CKMB, LDH, HBDH, PT, APTT, DDi, IL-6, IL-10, and IFN-γlevels (P < 0.05). In contrast, serum sIL-2R levels demonstrated a negative correlation with LY, HGB, ALB, Th17 cell populations, and Th17/Treg cell ratios (P < 0.05). Employing multivariate logistic regression, we identified serum sIL-2R concentrations as an independent risk factor for both disease activity and hepatic involvement in DM patients. Moreover, receiver operating characteristic (ROC) curve analyses revealed that serum sIL-2R levels significantly contributed to the differentiation of disease activity and the detection of liver involvement in DM patients, with areas under the ROC curve (AUC) of 0.757 (95% CI 0.630-0.884, P = 0.001) and 0.826 (95% CI 0.717-0.935, P < 0.001), respectively. This study highlights the potential utility of serum sIL-2R levels as a valuable biomarker for assessing disease activity and liver involvement in dermatomyositis. Elevated serum concentrations of sIL-2R were observed in patients with DM, exhibiting significant associations with Th17 cell populations and Th17/ Treg ratios. These findings indicate that sIL-2R may be implicated in the immunopathogenesis of DM, thereby warranting further investigation to elucidate its role in the disease process.

Is there an association between serum soluble interleukin-2 receptor levels and syndrome severity in persistent Complex Regional Pain Syndrome?

A potentially useful biomarker for Complex Regional Pain Syndrome (CRPS) is the serum soluble interleukin-2 receptor (sIL-2R) level, which is a marker for T-cell activation. Elevated serum sIL-2R levels have been described in CRPS patients compared to healthy controls. In T-cell mediated inflammatory diseases such as sarcoidosis and rheumatoid arthritis, the serum sIL-2R levels correlate with disease severity. In this study, we investigate whether an association exists between serum sIL-2R levels in CRPS patients and CRPS severity. A cross-sectional cohort study was conducted in a tertiary pain referral center in the Netherlands. Adult CRPS patients diagnosed by the IASP criteria were included between October 2018 until October 2022. The main study parameters were serum sIL-2R levels and the CRPS severity score. Fifty-three CRPS patients were included with a mean syndrome duration of 84 months (Q3 - Q1:180 - 48). The majority had persistent CRPS with a syndrome duration >1 year (n = 52, 98%). The median pain Numerical Rating Score (NRS) was 7 (Q3 - Q1: 8 - 5) and the mean CRPS severity score was 11 (SD ± 2.3). The median serum sIL-2R level was 330 U/mL (Q3 - Q1:451 - 256). No statistically significant correlation was observed between serum sIL-2R levels and the CRPS severity score (rs = 0.15, P = .28). Our findings suggest that serum sIL-2R levels cannot be used as a biomarker for syndrome severity in persistent CRPS (syndrome duration >1 year). Serial measurements of serum sIL-2R from early CRPS to persistent CRPS are needed to investigate whether serum sIL-2R levels can be used to monitor T-cell mediated inflammatory syndrome activity.

Role of Serum Soluble Interleukin-2 Receptor Level in the Diagnosis of Sarcoidosis: A Systematic Review and Meta-Analysis.

Serum Soluble Interleukin-2 Receptor (sIL-2R) levels are used clinically as a disease activity marker for systemic sarcoidosis. Studies have investigated the diagnostic role of serum soluble interleukin-2 receptor (sIL-2R) level for sarcoidosis relative to biopsy. We performed a systematic review and meta-analysis of studies evaluating the diagnostic utility of sIL-2R. We carried out an electronic search in Medline, Embase, Google Scholar, and Cochrane databases using keyword and Medical Subject Heading (MeSH) terms: sarcoidosis and sIL-2R. Studies evaluating the sIL-2R levels as a diagnostic tool in clinically diagnosed or biopsy-proven sarcoidosis patients compared to control groups with non-sarcoidosis patients were included. Forest plots were constructed using a random effect model depicting pooled sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy. We selected ten studies comprising 1477 patients, with 592 in the sarcoidosis group and 885 in the non- sarcoidosis group. Pooled sensitivity and specificity of sIL-2R levels were 0.88 (95% CI: 0.75-0.95) and 0.87 (95% CI 0.73-0.94) respectively. Pooled negative predictive value and positive predictive value were 0.91 (95% CI 0.77-0.97) and 0.85 (95% CI 0.59-0.96) respectively with diagnostic accuracy of 0.86 (95% CI 0.71- 0.93). In addition to its utility as a marker of sarcoidosis disease activity, sIL-2R has high diagnostic accuracy. Despite the limitations of the heterogenous sarcoidosis population and different sIL-2R cutoffs, our results suggest that sIL-2R is an important biomarker that can be used to confirm sarcoidosis diagnosis in unconfirmed or unclear cases.

Usefulness of Serum Soluble Interleukin-2 Receptor Levels for Differentiating between PCNSL and SCNSL.

Serum soluble interleukin-2 receptor (sIL-2R) is a practical tumor marker that is elevated in hematogenous tumors. The purpose of this study was to determine the usefulness of serum sIL-2R for differentiating among malignant brain tumors, including primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL). This study retrospectively investigated the sIL-2R levels in 130 patients with various types of malignant brain tumors, including PCNSL patients (n = 48) and SCNSL (n = 8); metastatic brain tumors (MTs, n = 16); and glioblastoma (GBM, n = 58). The median sIL-2R level (U/mL) of the PCNSL, SCNSL, MTs, and GBM groups were 489.7, 1024.8, 413.3, and 332.7 respectively. The sIL-2R level was significantly higher in the SCNSL group than in the PCNSL or other groups. The area under the ROC curve generated from the sIL-2R level was 0.826 (sensitivity: 0.875, specificity: 0.667, cutoff value: 521 U/mL) for differentiating SCNSL from PCNSL and 0.685 (sensitivity: 0.667, specificity: 0.707, cutoff value: 342 U/mL) for differentiating PCNSL from GBM. Measurement of sIL-2R level was convenient and useful to differentiate between SCNSL and PCSNL, both of which demand different treatment strategies.

Acquired L1196M ALK mutation in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma during alectinib administration.

Acquired L1196M ALK mutation in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma during alectinib administration.

Improving Prognosis of Aggressive Natural Killer Cell Leukemia in Japan

Introduction Aggressive natural killer cell leukemia (ANKL) is a rare leukemic form of mature NK cell neoplasm that is closely associated with the Epstein-Barr virus (EBV). Patients with ANKL show a fulminant clinical course and poor prognosis with a median overall survival (OS) of a few months after diagnosis. L-asparaginase (L-asp)-containing chemotherapies and allogeneic hematopoietic stem cell transplantation (HSCT) are considered as effective therapeutic strategies. However, owing to the rarity of this disease, the characteristics and outcomes of ANKL remain unclear. Methods Data of 103 patients diagnosed with ANKL between 2002 and 2021 from 64 hospitals were retrospectively analyzed. Diagnosis was based on the World Health Organization classification and was verified by two co-authors (AF and RS). Patients registered in our previous ANKL studies were excluded. Results Patient's median age was 50 years (range, 17-90 years), and males accounted for 58%. Twelve patients (12%) had a medical history of chronic active EBV infection (9%), severe mosquito bite allergy (5%), and chronic lymphoproliferative disorder of NK cells (1%). B symptoms were commonly observed at the time of diagnosis (89%). Performance status (PS) was poor (2-4) in more than half of patients (53%). The median percentage of ANKL cells was 20.0% (range, 0-93.4) in bone marrow (BM) and 10.3% (range, 0-89) in peripheral blood (PB). ANKL cells express CD2 (95%), CD7 (53%), CD16 (41%), CD56 (95%), and EBER (86%). Fifty-two patients analyzed (58%) had chromosomal abnormalities by G-banding method, including chromosome 17 abnormalities in 19, deletion of 6q in 11, and isochromosome 7 in 5. Blood tests at diagnosis typically showed pancytopenia with a median white blood cell count of 2,900/μl, hemoglobin level of 10.3g/dl, and platelets 4.3×104/μl. High serum lactate dehydrogenase and soluble interleukin-2 receptor level were also observed (median, 882U/l and 8,475U/dl, respectively). The most common extra-nodal site of involvement was the BM (100%), followed by the spleen (84%), liver (70%), and PB (59%). Median OS of the present cohort was 5.3 months, and 1-year OS was 25.7%. Prognosis was significantly better in patients who underwent HSCT than in those who did not undergo HSCT (P < 0.001). The median OS and 1-year OS were 12.0 months and 52.3% in the former group and 1.7 months and 3.8% in the latter. Eighty-three patients received multi-agents-containing chemotherapy, while the others received single agent or did not receive any anti-lymphoma chemotherapy owing to poor general condition. The most common first-line chemotherapy was the SMILE regimen (39%), followed by anthracycline-based regimens, mainly CHOP (24%), DeVIC (15%) and other L-asp-containing regimens (8%). The response rate was highest in patients treated with SMILE (66%), followed by those who received other L-asp-containing regimens (57%), DeVIC (36%) and anthracycline-based regimens (32%). OS was significantly better in patients who received SMILE than in those who did not receive SMILE (1-year OS 39.3% vs. 12.1%, P < 0.001, Figure). Furthermore, the HSCT rate was significantly higher in patients who received SMILE (68% vs. 26%, P < 0.001). Multivariate analysis using the Cox proportional hazards model showed good PS (0-1) (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.23-0.91, P = 0.03), administration of SMILE (HR 0.43, 95% CI 0.23-0.80, P = 0.009), and HSCT (HR 0.26, 95% CI 0.12-0.58, P = 0.001) were independent factors associated with favorable OS. Conclusion The present study showed better OS as compared with our previous study. The SMILE chemotherapy and HSCT were suggested to be key components of the therapeutic strategy for ANKL. Further studies are warranted to validate these findings. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Correlation between serum levels of PTX-3, SIL-2R, inflammatory markers, and APACHE II scores in patients with severe acute pancreatitis.

To investigate the correlation of serum pentraxin 3 (PTX-3), soluble interleukin-2 receptor (SIL-2R), C-reactive protein (CRP), procalcitonin (PCT) levels, and acute physiology and chronic health evaluation II (APACHE II) scores in patients with severe acute pancreatitis (SAP). A total of 30 patients with SAP from October 2020 to October 2021 were selected as the SAP group, and 42 patients with mild acute pancreatitis (MAP) or moderate-severe acute pancreatitis (MSAP) was selected as the control group. The serum levels of PTX-3, SIL-2R, CRP, PCT, and APACHE II scores were evaluated. The serum levels of PTX-3, SIL-2R, CRP, PCT, and APACHE II scores at admission in the SAP group were significantly higher than those in the control group (all P < .05). Spearman analysis showed that serum PTX-3, SIL-2R, CRP, and PCT levels were positively correlated with APACHE II scores (all P < .05). The mortality rate within 28 days was 26.7% in the SAP group; moreover, the serum PTX-3, SIL-2R, CRP, and PCT levels and APACHE II scores at admission in the death group were significantly higher than those in the survival group (all P < .05). The receiver operating curve showed that the combined prediction value of all indicators (PTX-3 + SIL-2R + CRP + PCT + APACHE II) was superior to the single indicators, and the diagnostic sensitivity and specificity were 90.9% and 84.2%, respectively. Serum PTX-3, SIL-2R, CRP, and PCT levels and APACHE II scores have high guiding significance in early diagnosis and prognostic evaluation of SAP patients.

Soluble interleukin-2 receptor serum levels facilitate prediction of relapses in subgroups of patients with juvenile idiopathic arthritis.

JIA is characterised by a chronic disease course. Once patients achieve a state of inactive disease, there are no established biomarkers to predict the further course of inflammation for these patients. Therefore, the purpose of this study was to quantify serum biomarkers during quiescent disease to evaluate their use in identifying JIA patients at risk for future disease flare. Patients with non-systemic JIA reaching inactive disease status were divided into two groups: 92 patients with future active disease after a median period of 6 months (range 3-9) and 80 patients with persistent inactive disease for the following period (median 11 months, range 7-16) according to the juvenile arthritis DAS (JADAS). Clinical parameters and serum levels of various biomarkers were measured in the state of inactive disease using immunoassays in both groups and were analysed for their potential to predict the further course of disease. Soluble interleukin-2 receptor (sIL-2R) serum levels were significantly higher in patients with future active disease (P = 0.021), which especially applied to patients with RF-negative polyarticular and extended oligoarticular JIA (P < 0.001). Higher sIL-2R serum levels during inactive disease were associated with a greater number of active joints at future active disease. Patients without clinical signs of disease activity already presented with increased sIL-2R serum levels several months before disease relapses, whereas conventional inflammation parameters were not elevated. Determination of sIL-2R serum levels during inactive disease may facilitate identifying patients with subclinical disease activity at risk for future active disease.

Clinical Effect of Laparoscopic Radical Surgery Combined with Neoadjuvant Chemotherapy in Treating Cervical Cancer and Its Influence on Postoperative Complications and Adverse Reaction Rates.

Background Cervical cancer, the only gynecological malignancy for which a clear pathogeny has been established, has an incidence rate only second to breast cancer. Objective In our study, we aim to investigate the clinical effect of laparoscopic radical surgery combined with neoadjuvant chemotherapy in treating cervical cancer and its influence on postoperative complications and adverse reaction rates. Methods Cervical cancer patients admitted to our hospital from August 2018 to May 2020 were retrospectively analyzed as the research object and divided into the control group and the experimental group by the draw method, with 50 cases in each group. The laparoscopic radical surgery was performed on the control group, and the laparoscopic radical surgery combined with neoadjuvant chemotherapy was performed on the experimental group to compare their effective rates, adverse reaction rates, postoperative complication rates, expression levels of serum tumor necrosis factor-α (TNF-α) and soluble interleukin-2 receptor (SIL-2R) inside the body before surgery and at one week after surgery, quality of life (QLI) scores, and Mental Status Scale in Nonpsychiatric Settings (MSSNS) scores. Results Compared with the control group, the experimental group obtained significantly higher effective rate and QLI scores (P < 0.05) and significantly lower adverse reaction rates, postoperative complication rates, expression levels of serum TNF-α and SIL-2R inside the body at one week after surgery, and MSSNS scores (P < 0.05), with statistical differences; before surgery, the TNF-α and SIL-2R expression levels of the two groups were not significantly different (P > 0.05), but the levels at one week after surgery were significantly lower than those before, indicating statistical significance (P < 0.05). Conclusion The clinical effect of laparoscopic radical surgery combined with neoadjuvant chemotherapy can obviously improve the effective rate of cervical cancer patients and lower the incidence rates of postoperative complications and adverse reactions.

Comparison of serum sIL-2R and LDH levels in patients with intravascular large B-cell lymphoma and patients with advanced stage diffuse large B-cell lymphoma.

Intravascular large B-cell lymphoma (IVL) is a rare type of lymphoma characterized by tumor growth selectively within the vessels. The 5th edition of the World Health Organization classification defines IVL as a large B-cell lymphoma, the same as diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS). Since the clinical manifestations of IVL are nonspecific, the diagnosis is time-consuming, and the course is often fatal. Serum soluble interleukin-2 receptor (sIL-2R) and serum lactate dehydrogenase (LDH) levels are known to be elevated in a variety of lymphomas. However, the mechanism of sIL-2R elevation in B-cell lymphomas is not fully understood. In this study, we analyzed the serum level of laboratory findings, including sIL-2R and LDH, as well as the presence of B symptoms in 39 patients with IVL, and compared them with 56 patients with stage IV DLBCL. Both sIL-2R and LDH levels were significantly higher in IVL than in DLBCL (p = 0.035 and p = 0.002, respectively). In IVL, there were no significant differences in both sIL-2R and LDH levels between patients with and without B symptoms (p = 0.206 and p = 0.441, respectively). However, in DLBCL, both sIL-2R and LDH levels were significantly higher in the presence of B symptoms (p = 0.001 and p < 0.001, respectively). The high sIL-2R and LDH levels in IVL may be related to the peripheral blood microenvironment, but further studies are needed to verify this.

SARS-COV-2 PNEUMONIA LEADING TO PROGRESSION OF PULMONARY SARCOIDOSIS

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: The implication of COVID 19 pneumonia on chronic inflammatory disorders is not clearly known. Due to a lack of data, it is difficult to predict the disease course post-COVID 19 pneumonia. Here, we present a case of stable sarcoidosis that progressed rapidly after COVID 19 pneumonia. CASE PRESENTATION: A 43-year-old male, with a history of sarcoidosis, briefly treated with steroids at initial diagnosis and in remission for the last six years, was admitted for dyspnea and hypoxia (room air oxygen saturation 83%) secondary to COVID 19 pneumonia diagnosed a week prior to admission. Chest X-ray on admission showed diffuse bilateral interstitial and airspace opacities. He was treated with dexamethasone and remdesevir. The clinical status of the patient improved after a week, and he was discharged on prednisone taper (10 mg for 5 days). Four weeks later, the patient had a recurrence of dyspnea on exertion with occasional hemoptysis. Computed Tomography (CT) scan of the chest showed honeycombing and reticulations in bilateral upper lobes, interstitial thickening, and worsening hilar and mediastinal lymphadenopathy (sarcoidosis Scadding stage IV). Labs were significant for elevated serum soluble interleukin-2 (IL-2) receptor and calcitriol levels. Pulmonary function test showed a restrictive defect with reduced diffusion capacity. The patient was started on prednisone. Repeat CT scan after three months showed improvement in ground-glass opacities and stable scarring. Fine needle aspiration biopsy of subcarinal lymph node confirmed non-caseating granulomatous inflammation. The patient was started on mycophenolate mofetil, tapered off prednisone, and is being evaluated for a lung transplant. DISCUSSION: The main pathogenesis related to sarcoidosis is the formation of granulomas due to sustained host immune system stimulation from various known and unknown antigens. Activation of the immune system as evidenced by elevated inflammatory makers in viral infections may in turn precipitate the relapse and progression of inflammatory disorders such as sarcoidosis. It is difficult to distinguish between the sequela of COVID 19 pneumonia and sarcoidosis progression. CT scan findings in fibrotic sarcoidosis have upper lobe predilection. However, the distribution of ground-glass opacities and fibrosis in COVID 19 pneumonia is usually peripheral and may have lower lobe predilection. Close monitoring is important to look for activation of sarcoidosis post COVID 19 pneumonia. CONCLUSIONS: Implications of COVID 19 infection on pathogenesis and progression of sarcoid are important to understand, and more research is required so that clinicians can be vigilant about worsening pulmonary function and intervene in a timely manner. REFERENCE #1: Ramdani H, Benelhosni K, Moatassim Billah N, Nassar I. COVID-19 pneumonia in a patient with sarcoidosis: A case report. Clin Case Rep. 2020 Dec 23;9(2):910-913. REFERENCE #2: Tana C, Mantini C, Cipollone F, Giamberardino MA. Chest Imaging of Patients with Sarcoidosis and SARS-CoV-2 Infection. Current Evidence and Clinical Perspectives. Diagnostics (Basel). 2021 Jan 27;11(2):183. DISCLOSURES: No relevant relationships by Salim Daouk, source=Web Response No relevant relationships by Samiksha Gupta, source=Web Response No relevant relationships by Ahmad Hassan, source=Web Response No relevant relationships by SYED HUSSAIN, source=Web Response No relevant relationships by Miloni Parmar, source=Web Response

Pretreatment levels of serum soluble interleukin-2 receptor are useful in selecting the treatment regimen for newly diagnosed advanced-stage follicular lymphoma with low tumor burden.

High pre-treatment serum soluble interleukin-2 receptor (sIL-2R) levels are associated with poor overall survival (OS) of patients with newly diagnosed follicular lymphoma (FL). We evaluated the usefulness of pre-treatment sIL-2R levels in selecting a treatment regimen for advanced-stage FL with low tumor burden (FL-LTB). This retrospective, multicenter observational study enrolled consecutive patients who received a rituximab-containing regimen for newly diagnosed advanced stage FL-LTB (grade 1-3a) between 2008 and 2018. We applied a previously reported cut-off value of 1800IU/mL for sIL-2R. A total of 211 patients were eligible for the analysis. Among patients with high sIL-2R (47 patients, 22.3%), the OS rates for patients treated by rituximab monotherapy (R-mono) (11 patients) were significantly lower than those treated by rituximab-combination chemotherapy (R-chemo) (36 patients): 5-year OS rates were 66.7% and 94.4%, respectively (P = 0.007). Among patients with low sIL-2R (164 patients, 77.7%), OS rates were comparably good between the R-mono group (34 patients) and the R-chemo group (130 patients): 5-year OS rates were 100% and 98.3%, respectively (P = 0.38). Our results suggest that R-chemo may yield better OS than R-mono for patients with newly diagnosed advanced-stage FL-LTB and high pre-treatment serum sIL-2R levels.

Overall survival and post-spontaneous regression relapse-free survival of patients with lymphoproliferative disorders associated with rheumatoid arthritis: a multi-center retrospective cohort study.

To clarify factors affecting 5-year survival rates and relapse rates after spontaneous regression (SR) of lymphoproliferative disorders (LPDs) in patients with rheumatoid arthritis (RA). This retrospective longitudinal study comprised 232 patients with RA diagnosed with LPDs between January 2000 and March 2017 at eight hospitals in Japan. The Kaplan-Meier method was used to analyze survival and the Cox proportional hazard model was applied to identify predictive factors. Among all patients, 1-, 2- and 5-year overall survival rates were 89.5%, 86.1%, and 78.2%, respectively. Multivariable analysis revealed four 5-year survival risk factors assessed at diagnosis: age above 70 years (p = .002), deep lymphadenopathy and/or more than one extranodal lesion (p = .008), Eastern Cooperative Oncology Group/Zubrod performance status of 2-4 (p = .004), and classic Hodgkin lymphoma (CHL) histology (p = .047). Among 143 patients who achieved SR, 2- and 5-year relapse rates were 14.2% and 24.9%, respectively. CHL histology (p = .003) and serum soluble interleukin-2 receptor levels exceeding 2000 IU/L (p = .014) were associated with post-SR relapse-free survival. Blood lymphocyte counts were significantly lower at relapse than at 3-6 months prior (p < .001). Assessment of the above risk factors and routine inspection of blood lymphocyte counts could aid in the care management of LPDs in RA.

Prolonged, Continuous Treatment of Hairy Cell Leukemia Patients With Recombinant Interferon-α2a

AbstractInterferons are not curative in hairy cell leukemia (HCL), and retreatment is necessary in most patients whose therapy is stopped. In an attempt to maintain or improve responses, we administered recombinant interferon-α2a (rlFN-α2a) continuously to patients with HCL who initially responded to this therapy. Of 53 evaluable patients enrolled in this study, 32 have received rlFN-α2a continuously for a median of 5 years. Patients received 3 million units of rlFN-α2a subcutaneously (SC) daily for 6 months, followed, in responding patients, by the same dose three times weekly. Twenty-one patients (40%) discontinued IFN after a median of 29 months, seven of whom developed resistant disease in association with anti-IFN antibodies. Treatment produced high response rates: complete response plus partial response (CR + PR) = 40 of 53 (76%), CR + PR + minor response (MR) = 43 of 53 (82%), with no differences in response rates between patients with and without splenectomy. Sixteen patients who had MR at 18 months had PR with prolonged treatment, nine of whom had a significant further reduction in the hairy cell infiltrate in the bone marrow (BM). The median granulocyte and platelet counts have continued to increase and the median serum soluble interleukin-2 receptor (slL-2R) level has continued to decrease with prolonged treatment. Two patients developed erythrocytosis that may be treatment related, but no other new toxicities were noted with prolonged treatment. We conclude that prolonged, continuous rlFN-α2a treatment has acceptable toxicity, is not associated with late development of IFN resistance, and results in continued hematologic improvement with time on treatment. This is a US government work. There are no restrictions on its use.

Mogamulizumab for adult T-cell leukemia-lymphoma: a multicenter prospective observational study

AbstractMonitoring of Immune Responses Following Mogamulizumab-Containing Treatment in Patients with Adult T-Cell Leukemia-Lymphoma (ATL) (MIMOGA) is a multicenter prospective observational study to establish the most effective and safe treatment strategy using mogamulizumab for ATL patients (UMIN000008696). Mogamulizumab-naive patients were enrolled (n = 102), of whom 101 received mogamulizumab-containing treatment (68 acute, 18 lymphoma, 12 chronic, and 3 smoldering subtypes). At enrollment, there was a significant inverse correlation between serum soluble interleukin-2 receptor (sIL-2R) levels and percentages of Tax-specific cytotoxic T lymphocytes (Tax-CTLs) in the entire lymphocyte population or in the CD8+ T cell subset, but there was not a correlation with cytomegalovirus pp65–specific cytotoxic T lymphocytes (CMV-CTLs). The overall response rate was 65%, and median progression-free survival and overall survival (OS) were 7.4 and 16.0 months, respectively. A higher percentage of Tax-CTLs, but not CMV-CTLs, within the entire lymphocyte population or in the CD8+ T cell subset was significantly associated with longer survival. Multivariate analysis identified the clinical subtype (acute or lymphoma type), a higher sIL-2R level, and a lower percentage of CD2−CD19+ B cells in peripheral blood mononuclear cells as significant independent unfavorable prognostic factors for OS. This indicates that a higher percentage of B cells might reflect some aspect of a favorable immune status leading to a good outcome with mogamulizumab treatment. In conclusion, the MIMOGA study has demonstrated that mogamulizumab exerts clinically meaningful antitumor activity in ATL. The patient's immunological status before mogamulizumab was significantly associated with treatment outcome. Further time series immunological analyses, in addition to comprehensive genomic analyses, are warranted.

Serum Soluble Interleukin-2 Receptor Does Not Differentiate Complex Regional Pain Syndrome from Other Pain Conditions in a Tertiary Referral Setting.

Previously, we showed that serum soluble interleukin-2 receptor (sIL-2R) levels, a marker for T-cell activation, were higher in complex regional pain syndrome (CRPS) patients than in healthy controls, suggesting pathogenic T-cell activation in CRPS. Additionally, sIL-2R levels discriminated well between CRPS and healthy controls with a high sensitivity (90%) and specificity (89.5%), suggesting a possible role for sIL-2R in the diagnosis of CRPS. In order to further validate this marker in the diagnostic workup of CRPS, we conducted this prospective cohort study in which we determined sIL-2R levels in patients that were referred to our tertiary referral center with a suspicion of CRPS in a limb, and subsequently compared sIL-2R levels between the patients that were diagnosed with CRPS (CRPS group) and those who were not (no CRPS group). A group of anonymous blood bank donors were used as a healthy control group. Furthermore, we explored the relationship between sIL-2R and CRPS disease severity using the CRPS severity score. Median sIL-2R levels of both the CRPS group (2809.0 pg/ml; Q3-Q1: 3913.0-1589.0) and no CRPS group (3654.0 pg/ml; Q3-Q1: 4429.0-2095.5) were significantly higher than that of the control group (1515.0 pg/ml; Q3-Q1: 1880.0-1150.0): CRPS vs. controls, p < .001; no CRPS vs. controls, p < 0.001. Serum sIL-2R levels did not differ significantly between the CRPS and no CRPS group. A statistically significant negative correlation was observed between sIL-2R levels and the CRPS severity score (rs = −0.468, p = 0.024). Our results confirm our previous findings of higher sIL-2R levels in CRPS patients than in healthy controls. We further showed that serum sIL-2R cannot differentiate between CRPS and other pain conditions of a limb in a tertiary referral setting. Interestingly, a negative correlation was found between sIL-2R and CRPS disease severity; this finding warrants further research into the relationship between sIL-2R and CRPS disease severity.

Ocular sarcoidosis: clinical experience and recent pathogenetic and therapeutic advancements

PurposeTo describe the ocular manifestations in a cohort of patients with systemic sarcoidosis (SS). Recent advances in the pathophysiology, diagnosis, and therapy of SS are also discussed.MethodsData from 115 Italian patients diagnosed between 2005 and 2016 were retrospectively reviewed. All but the first 17 patients underwent a comprehensive ophthalmologic examination. The diagnosis was based on clinical features, the demonstration of non-caseating granulomas in biopsies from involved organs, and multiple imaging techniques. Data on broncho-alveolar lavage fluid analysis, calcemia, calciuria, serum angiotensin-converting enzyme levels and soluble interleukin-2 receptor levels were retrieved when available.ResultsOcular involvement, detected in 33 patients (28.7%), was bilateral in 29 (87.9%) and the presenting feature in 13 (39.4%). Anterior uveitis was diagnosed in 12 patients (36.4%), Löfgren syndrome and uveoparotid fever in one patient each (3%), intermediate uveitis in 3 patients (9.1%), posterior uveitis in 7 (21.2%), and panuveitis in 9 (27.3%). First-line therapy consisted of corticosteroids, administered as eyedrops (10 patients), sub-Tenon’s injections (1 patient), intravitreal implants (9 patients), or systemically (23 patients). Second-line therapy consisted of steroid-sparing immunosuppressants, including methotrexate (10 patients) and azathioprine (10 patients). Based on pathogenetic indications that tumor necrosis factor (TNF)-α is a central mediator of granuloma formation, adalimumab, targeting TNF-α, was employed in 6 patients as a third-line agent for severe/refractory chronic sarcoidosis.ConclusionUveitis of protean type, onset, duration, and course remains the most frequent ocular manifestation of SS. Diagnostic and therapeutic advancements have remarkably improved the overall visual prognosis. An ophthalmologist should be a constant component in the multidisciplinary approach to the treatment of this often challenging but intriguing disease.

Pretreatment serum soluble interleukin-2 receptor level predicts survival in patients with newly diagnosed follicular lymphoma

This retrospective, multicenter observational study investigated the prognostic value of pretreatment serum soluble interleukin-2 receptor (sIL-2R) level for outcomes of newly diagnosed follicular lymphoma (FL) grade 1-3a who required treatment at diagnosis. A total of 628 patients were recorded, and 502 of these were eligible for analysis. Patients were divided into four quartiles, based on their serum sIL-2R levels as follows: Q1 (sIL-2R < 520 IU/mL), Q2 (520 ≤ sIL-2R < 1030 IU/mL), Q3 (1030 ≤ sIL-2R < 2530 IU/mL) and Q4 (sIL-2R ≥ 2530 IU/mL). Using a multivariable Cox proportional-hazards model, we showed the adjusted probability of overall survival (OS) decreased with increasing serum sIL-2R levels (p for trend = .007). Similar trends were observed for disease-specific survival (DSS) and progression-free survival (PFS). In conclusion, pretreatment serum sIL-2R levels significantly and dose-dependently associate with worse outcomes (OS, DSS and PFS) of patients with newly diagnosed FL.