Enhancer of Zeste Homolog 2 Inhibitor SHR2554 in Relapsed or Refractory Peripheral T-cell Lymphoma: Data from the First-in-Human Phase I Study.

PURPOSE: Patients with peripheral T-cell lymphomas (PTCL) in the relapsed or refractory (r/r) setting have only a limited number of therapies available, and the prognosis is extremely poor. SHR2554 is an oral inhibitor against EZH2, a rational therapeutic target for lymphomas. PATIENTS AND METHODS: This was a multicenter, two-part, phase I study of SHR2554 in r/r mature lymphoid neoplasms. In part I, 350 mg twice daily was established as the recommended phase II dose (RP2D) based on the findings during dose escalation and expansion; subsequently, selected lymphoma subtypes were recruited in clinical expansion cohorts to receive SHR2554 at RP2D. Here, we provide an in-depth assessment of SHR2554 at RP2D in subpopulation with r/r PTCL. RESULTS: Twenty-eight patients were included for analysis (17 angioimmunoblastic T-cell lymphoma and 11 not otherwise specified). Eighteen (64%) patients had received ≥2 lines of previous anticancer therapies. The objective response rate was 61% [95% confidence interval (CI), 41-78]. Responses were still ongoing in 59% (10/17) of the responders; estimated median duration of response was 12.3 months (95% CI, 7.4-not reached). Median progression-free survival was 11.1 months (95% CI, 5.3-22.0), and 12-month overall survival rate was 92% (95% CI, 72-98). The most common grade 3 or 4 treatment-related adverse events were decreased platelet count [nine (32%)] as well as decreased white blood cell count, decreased neutrophil count, and anemia [four (14%) for each]. No treatment-related deaths were reported. CONCLUSIONS: This extended follow-up analysis further supports SHR2554 as a therapeutic opportunity for patients with r/r PTCL.

Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, in patients with refractory or relapsed peripheral T-cell lymphoma (JACKPOT8 Part B): a single-arm, multinational, phase 2 study.

BACKGROUND: Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, has shown encouraging anti-tumour activity in heavily pre-treated patients with relapsed or refractory peripheral T-cell lymphoma in a phase 1 study (JACKPOT8 Part A). Here, we report the full analysis of a phase 2 study, in which we assessed the anti-tumour activity of golidocitinib in a large multinational cohort of patients. METHODS: We did a single-arm, multinational, phase 2 trial (JACKPOT8 Part B) in 49 centres in Australia, China, South Korea, and the USA. Eligible patients were adults (aged ≥18 years) with relapsed or refractory peripheral T-cell lymphoma who had received at least one previous line of systemic therapy and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were given oral golidocitinib 150 mg once daily until disease progression or other discontinuation criteria were met. The primary endpoint was the CT-based objective response rate, assessed by an independent review committee (IRC) per Lugano 2014 classification. The activity analysis set included all patients who received at least one dose and whose pathological diagnosis of peripheral T-cell lymphoma had been retrospectively confirmed by a central laboratory and who had at least one measurable lesion at baseline assessed by IRC. The safety analysis set included all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT04105010, and is closed to accrual and follow-up is ongoing. FINDINGS: Between Feb 26, 2021, and Oct 12, 2022, we assessed 161 patients for eligibility, of whom 104 (65%) were enrolled and received at least one dose of study drug; the activity analysis set included 88 (85%) patients (median age 58 years [IQR 51-67], 57 [65%] of 88 were male, 31 [35%] were female, and 83 [94%] were Asian). As of data cutoff (Aug 31, 2023; median follow-up was 13·3 months [IQR 4·9-18·4]), per IRC assessment, the objective response rate was 44·3% (95% CI 33·7-55·3; 39 of 88 patients, p<0·0001), with 21 (24%) patients having a complete response and 18 (20%) having a partial response. In the safety analysis set, 61 (59%) of 104 patients had grade 3-4 drug-related treatment-emergent adverse events. The most common grade 3-4 drug-related treatment-emergent adverse events were neutrophil count decreased (30 [29%]), white blood cell count decreased (27 [26%]), lymphocyte count decreased (22 [21%]), and platelet count decreased (21 [20%]), which were clinically manageable and reversible. 25 (24%) patients had treatment-related serious adverse events. Deaths due to treatment-emergent adverse events occurred in three (3%) patients: two (2%) due to pneumonia (one case with fungal infection [related to golidocitinib] and another one with COVID-19 infection) and one (1%) due to confusional state. INTERPRETATION: In this phase 2 study, golidocitinib showed a favourable benefit-risk profile in treating relapsed or refractory peripheral T-cell lymphoma. The results of this study warrant further randomised clinical studies to confirm activity and assess efficacy in this population. FUNDING: Dizal Pharmaceutical.

Analysis of Fever Following Bronchoscopy and Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration.

Objective: Bronchoscopy and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are two essential methods for obtaining the pathological diagnosis of central lung masses or hilar and mediastinal lymphadenopathy. We can observe that many patients have a fever after examinations, but the pathogenesis is not yet fully clear. We tried to comprehensively assess the occurrence of postoperative fever and bacterial infections in patients undergoing bronchoscopy and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) procedures. Methods: We retrospectively analyzed 512 patients undergoing bronchoscopy or EBUS-TBNA examination. According to examination methods, all patients were classified into three groups: Only perform bronchoscopy examination (BO) group (122 cases)，both perform bronchoscopy and biopsy (BB) group (262 cases), and EBUS-TBNA after bronchoscopy (EBUS) group (128 cases). Peripheral blood leucocyte, neutrophil count, and serum IL-6 test results were obtained before and after the examination. A blood culture was performed when the body temperature was higher than 38.5°C. Results: Among the three groups, the onset time (5.5h), average duration (6h), and peak temperature (37.7°C) of fever in the BO group were lower than those in the BB and EBUS groups. Still, there was no significant difference in onset time (11.66h, 11.83h), average duration (12.86h, 13.56h), and peak temperature (39.1°C, 39.1°C) between the BB group and EBUS group. There was no significant difference in the peripheral blood leukocyte count, neutrophil count or IL-6 level before the operation (P > .05). Compared with the preoperative, the leukocyte count, neutrophil count and IL-6 level in the three groups were increased after the operation (P < .05). Positive blood cultures were diagnosed as normal oropharyngeal flora. Conclusions: Postoperative fever after bronchoscopy is a relatively common complication, most of which do not require special treatment. Individuals with concomitant diseases such as diabetes may have postoperative infections after EBUS-TBNA, and they should be emphatically observed. The findings could potentially extend to similar diagnostic procedures or situations in pulmonary medicine. Understanding the risk factors associated with postoperative fever can help healthcare providers manage patient expectations and monitor certain groups more closely.

A nomogram for predicting the rapid progression of diffuse large B-cell lymphoma established by combining baseline PET/CT total metabolic tumor volume, lesion diffusion, and TP53 mutations.

OBJECTIVES: This study aimed to integrate positron emission tomography/computed tomography (PET/CT) metrics and genetic mutations to optimize the risk stratification for diffuse large B-cell lymphoma (DLBCL) patients. METHODS: The data of 94 primary DLBCL patients with baseline PET/CT examination completed in the Shandong Cancer Hospital and Institute (Jinan, China) were analyzed to establish a training cohort. An independent cohort of 45 DLBCL patients with baseline PET/CT examination from other hospitals was established for external validation. The baseline total metabolic tumor volume (TMTV) and the largest distance between two lesions (Dmax) standardized by patient body surface area (SDmax) were calculated. The pretreatment pathological tissues of all patients were sequenced by a lymphopanel including 43 genes. RESULTS: The optimal TMTV cutoff was 285.3 cm3 and the optimal SDmax cutoff was 0.135 m-1 . TP53 status was found as an independent predictive factor significantly affecting complete remission (p = 0.001). TMTV, SDmax, and TP53 status were the main factors of the nomogram and could stratify the patients into four distinct subgroups based on their predicted progression-free survival (PFS). The calibration curve demonstrated satisfactory agreement between the predicted and actual 1-year PFS of the patients. The receiver operating characteristic curves showed this nomogram based on PET/CT metrics and TP53 mutations had a better predictive ability than the clinic risk scores. Similar results were identified upon external validation. CONCLUSIONS: The nomogram based on imaging factors and TP53 mutations could lead to a more accurate selection of DLBCL patients with rapid progression, to increase tailor therapy.

The Oral PI3Kδ Inhibitor Linperlisib for the Treatment of Relapsed and/or Refractory Follicular Lymphoma: A Phase II, Single-Arm, Open-Label Clinical Trial.

PURPOSE: To investigate the efficacy and safety of the novel orally active PI3Kδ inhibitor in relapsed and/or refractory patients with follicular lymphoma (FL) who had received at least two prior systemic treatments. PATIENTS AND METHODS: Histologically confirmed relapsed and/or refractory patients with FL with disease progression after receiving second-line or greater systemic therapy were enrolled. Linperlisib was administered at 80 mg every day, orally in a 28-day cycle until disease progression or intolerable toxicity occurred. The primary outcome for the study was the objective response rate (ORR), with secondary outcomes including the duration of response (DOR), progression-free survival (PFS), overall survival (OS), disease control rate, and drug safety profile. RESULTS: Of 114 screened relapsed and/or refractory patients with FL, 84 were enrolled in the full analysis set (FAS). The ORR of the 84 FAS patients was 79.8% [95% confidence interval (CI), 69.6-87.8, 67 patients], with 13 patients (15.5%) achieving a complete response and 54 patients (64.3%) with a partial response. The median DOR was 12.3 months (95% CI, 9.3-15.9). The median PFS was 13.4 months (95% CI, 11.1-16.7). The 12-month OS rate was 91.4% (95% CI, 82.7-95.8) and a median OS not reached by 42 months. The most frequent (>3%) treatment-related adverse events Grade ≥3 were infectious pneumonia (19.0%), neutropenia (15.5%), decreased lymphocyte count (4.8%), decreased leukocyte count (4.8%), increased lipase (3.6%), decreased platelet count (3.6%), hypertriglyceridemia (3.6%), and interstitial lung disease (3.6%). CONCLUSIONS: Linperlisib demonstrated compelling clinical activity and manageable tolerability for relapsed and/or refractory patients with FL who had received at least two prior systemic therapies.

Molecular subtypes and a prognostic model for hepatocellular carcinoma based on immune- and immunogenic cell death-related lncRNAs.

Background: Accumulating evidence shows that immunogenic cell death (ICD) enhances immunotherapy effectiveness. In this study, we aimed to develop a prognostic model combining ICD, immunity, and long non-coding RNA biomarkers for predicting hepatocellular carcinoma (HCC) outcomes. Methods: Immune- and immunogenic cell death-related lncRNAs (IICDLs) were identified from The Cancer Genome Atlas and Ensembl databases. IICDLs were extracted based on the results of differential expression and univariate Cox analyses and used to generate molecular subtypes using ConsensusClusterPlus. We created a prognostic signature based on IICDLs and a nomogram based on risk scores. Clinical characteristics, immune landscapes, immune checkpoint blocking (ICB) responses, stemness, and chemotherapy responses were also analyzed for different molecular subtypes and risk groups. Result: A total of 81 IICDLs were identified, 20 of which were significantly associated with overall survival (OS) in patients with HCC. Cluster analysis divided patients with HCC into two distinct molecular subtypes (C1 and C2), with patients in C1 having a shorter survival time than those in C2. Four IICDLs (TMEM220-AS1, LINC02362, LINC01554, and LINC02499) were selected to develop a prognostic model that was an independent prognostic factor of HCC outcomes. C1 and the high-risk group had worse OS (hazard ratio > 1.5, p < 0.01), higher T stage (p < 0.05), higher clinical stage (p < 0.05), higher pathological grade (p < 0.05), low immune cell infiltration (CD4+ T cells, B cells, macrophages, neutrophils, and myeloid dendritic cells), low immune checkpoint gene expression, poor response to ICB therapy, and high stemness. Different molecular subtypes and risk groups showed significantly different responses to several chemotherapy drugs, such as doxorubicin (p < 0.001), 5-fluorouracil (p < 0.001), gemcitabine (p < 0.001), and sorafenib (p < 0.01). Conclusion: Our study identified molecular subtypes and a prognostic signature based on IICDLs that could help predict the clinical prognosis and treatment response in patients with HCC.

An enzyme-activated two-photon ratiometric fluorescent probe with lysosome targetability for imaging ß-glucuronidase in colon cancer cells and tissue.

Colon cancer is a malignant neoplasm with high mortality that has seriously threatened human life. Accumulating evidence reveals that the ß-glucuronidase (GLU), a lysosomal exoglycosidase enzyme, plays important roles in the pathological progression of colon cancer. Unfortunately, understanding the pathological roles of GLU remains a challenge due to the lack of effective detection methods for visualization the fluctuations of GLU in tissues. In this paper, based on hydrolysis function of GLU, an enzyme-activated ratiometric two-photon (TP) fluorescent probe (RN-GLU) was designed. RN-GLU was synthesized by introducing a glucopyranuronic acid methyl ester as the recognition group and 1, 8-naphthalimide as a TP fluorophore. In the presence of GLU, the trigger group was removed made an ICT process occurred induced enhancement of fluorescence ratio (I553 nm/I441 nm, 214-fold). Probe RN-GLU displayed low detection limit (1.2 × 10-2 µg/L) and rapid detection to GLU in vitro through a ratiometric response mode. Meanwhile, RN-GLU exhibited high selectivity for GLU and showed nearly no response to other relevant biological species. The imaging results demonstrated that RN-GLU could be applied for ratiometric monitoring of endogenous GLU levels in HCT116 cells with good lysosome targetable ability. Due to its two-photon excitation, RN-GLU could monitor GLU in colon cancer tumor tissue with good penetration ability (imaging depth of 200 µm). RN-GLU could be developed as a potential method for evaluating and confirming the functions of GLU in colon cancer diagnosis and complex biosystem.

Case report: Successful management of a refractory double-expressor diffuse large B-cell lymphoma patient under the guidance of in vitro high-throughput drug sensitivity test.

Introduction: Double-expressor diffuse large B-cell lymphoma (DEL), harboring double expression of MYC and BCL2, has an inferior prognosis following standard first-line therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). We initiated a clinical trial to treat newly diagnosed DEL with R-CHOP plus Bruton's tyrosine kinase (BTK) inhibitor (BTKi) zanubrutinib (ZR-CHOP) and achieved a high complete response (CR) rate while four patients progressed during therapy, one of them carrying ATM and CD58 mutations. We applied an in vitro high-throughput drug sensitivity test for the prediction of clinical responses to different drugs in this patient. Case presentation: We report a 30-year-old female patient diagnosed with stage III (DEL), with ATM and CD58 mutations. The patient achieved partial response (PR) after two cycles of ZR-CHOP and remained PR after four cycles of ZR-CHOP, while the disease progressed after six cycles of ZR-CHOP. High-throughput drug screening using a panel of 117 compounds identified a range of therapies with efficacy for this patient. The primary tumor cells showed moderate sensitivity to bortezomib, thalidomide, and gemcitabine as a single agent and bortezomib, thalidomide, and dexamethasone (VTD) as a combined regimen. The patient was treated with two cycles of VTD regimen (bortezomib 1.3 mg/m2, d1, 4, 8, 11; thalidomide 100 mg, d1-21; dexamethasone 20 mg, d1, 2, 4, 5, 8, 9) and achieved PR with only a small lesion left. Another two cycles of VTD plus gemcitabine were then administered, and the patient achieved CR. Stem cells were mobilized, and autologous hematopoietic stem cell transplantation was carried out afterward. The patient remained CR for more than 3 months after transplantation. Conclusion: In this article, we present a first-line chemoresistant DEL patient with ATM and CD58 mutations who was treated successfully with VTD plus gemcitabine under the guidance of in vitro high-throughput drug sensitivity test.

Novel Implications of MicroRNAs, Long Non-coding RNAs and Circular RNAs in Drug Resistance of Esophageal Cancer.

Esophageal cancer is the eighth most common malignancy and the sixth leading cause of cancer-related deaths worldwide. Chemotherapy based on platinum drugs, 5-fluorouracil, adriamycin, paclitaxel, gemcitabine, and vinorelbine, as well as targeted treatment and immunotherapy with immune checkpoint inhibitors improved the prognosis in a portion of patients with advanced esophageal cancer. Unfortunately, a number of esophageal cancer patients develop drug resistance, resulting in poor outcomes. Multiple mechanisms contributing to drug resistance of esophageal cancer have been reported. Notably, non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), have been identified to play crucial roles in modulating esophageal cancer drug resistance. In the present review, we highlight the underlying mechanisms how miRNAs, lncRNAs, and circRNAs impact the drug resistance of esophageal cancer. Several miRNAs, lncRNAs, and circRNAs may have potential clinical implications as novel biomarkers and therapeutic targets for esophageal cancer.

Phase 1 clinical trial of the PI3Kδ inhibitor YY-20394 in patients with B-cell hematological malignancies.

YY-20394, an oral phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor, was investigated in a first-in-human study of patients with relapsed or refractory B-cell malignancies. During dose escalation, 25 patients received 20-200 mg of YY-20394 daily. The primary outcome measures were tolerability and dose-limiting toxicity (DLT). The secondary outcomes were pharmacokinetic parameters, progression-free survival (PFS) and the objective response rate (ORR). Since no patients experienced DLT, the maximum tolerated dose (MTD) was not reached. The majority (≥ 5%) of drug-related adverse events were ≥ grade III, being neutropenia (44.0%), pneumonia (16.0%), hyperuricemia (12.0%), lymphocythemia (8.0%), leukopenia (8.0%) and pneumonitis (8.0%). The overall ORR was 64.0% (95% confidence interval (CI): 45.2, 82.8%) including 5 patients with complete remission (CR), 11 with partial remission (PR), 2 with stable disease (SD) and 7 with progressive disease (PD), while the disease control rate (DCR) was 72.0% (95% CI: 54.4, 89.6%). The ORR of 10 patients with follicular lymphoma was 90%. The median PFS time was 255 days. One PR patient with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who received 40 mg q.d. had a durable response of around 36 months. The median PFS time of 10 patients with follicular lymphoma was 300 days. A recommended phase 2 dose of 80 mg q.d. was established. Considering that YY-20394 was well-tolerated with promising preliminary efficacy, further development is warranted.Trial registration clinicaltrials.gov, NCT03757000, retrospectively registered, November 28, 2018, https://clinicaltrials.gov/ct2/show/NCT03757000?term=NCT03757000&draw=2&rank=1 .

Prophylaxis of neutropenia with mecapegfilgrastim in patients with non-myeloid malignancies: a real-world study.

BACKGROUND: Chemotherapy-induced neutropenia is commonly encountered in clinical practice. The management of neutropenia has been evolving from short-acting granulocyte colony-stimulating factors (G-CSFs) to long-acting G-CSFs. However, an evaluation of the safety and effectiveness of long-acting G-CSFs in clinical practice is still lacking. METHODS: This multicenter, non-interventional study was aimed at exploring the safety and effectiveness of mecapegfilgrastim in different cancer patients in China. All patients provided written informed consent prior to the study and were treated according to routine clinical practice. Different prophylactic strategies (primary or secondary prophylaxis) were also compared. RESULTS: This study included 638 patients from May 2019 to November 2020. More than half of the participants were breast cancer patients. The mean age of all the patients was 56 years. White blood cell increase (6.2%) was the most frequently reported adverse event (AE) possibly related to the study drug. No unexpected AEs were reported. Grade ≥3 neutropenia in chemotherapy treatment cycle 1 was reported in 36 (5.6%) patients. Incidence of grade ≥3 neutropenia in cycle 1 in the primary and secondary prophylaxis subgroups were of 4.3% and 9.2%, respectively. A decreasing trend of severe neutropenia incidence was observed from cycle 1 to cycle 4. CONCLUSIONS: Mecapegfilgrastim was generally well tolerated, and no unexpected AEs were observed in this study. Primary administration of mecapegfilgrastim led to a lower incidence of neutropenia than did secondary administration. Continuous administration of mecapegfilgrastim could keep the incidence of neutropenia to a relatively low level.

The combination of chidamide with the CHOEP regimen in previously untreated patients with peripheral T-cell lymphoma: a prospective, multicenter, single arm, phase 1b/2 study.

OBJECTIVE: To assess the efficacy and safety of the novel histone deacetylase inhibitor, chidamide, in combination with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (Chi-CHOEP) for untreated peripheral T-cell lymphoma (PTCL). METHODS: A prospective, multicenter, single arm, phase 1b/2 study was conducted. A total of 128 patients with untreated PTCL (18-70 years of age) were enrolled between March 2016 and November 2019, and treated with up to 6 cycles with the Chi-CHOEP regimen. In the phase 1b study, 3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximum-tolerated dose and recommended phase 2 dose (RP2D). The primary endpoint of the phase 2 study was 2-year progression-free survival (PFS). RESULTS: Fifteen patients were enrolled in the phase 1b study and the RP2D for chidamide was determined to be 20 mg, twice a week. A total of 113 patients were treated at the RP2D in the phase 2 study, and the overall response rate was 60.2%, with a complete response rate of 40.7%. At a median follow-up of 36 months, the median PFS was 10.7 months, with 1-, 2-, and 3-year PFS rates of 49.9%, 38.0%, and 32.8%, respectively. The Chi-CHOEP regimen was well-tolerated, with grade 3/4 neutropenia occurring in approximately two-thirds of the patients. No unexpected adverse events (AEs) were reported and the observed AEs were manageable. CONCLUSIONS: This large cohort phase 1b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.

Three-Dimensional Culture Decreases the Angiogenic Ability of Mouse Macrophages.

Macrophages play important roles in angiogenesis; however, previous studies on macrophage angiogenesis have focused on traditional 2D cultures. In this study, we established a 3D culture system for macrophages using collagen microcarriers and assessed the effect of 3D culture on their angiogenic capabilities. Macrophages grown in 3D culture displayed a significantly different morphology and arrangement under electron microscopy compared to those grown in 2D culture. Tube formation assays and chick embryo chorioallantoic membrane assays further revealed that 3D-cultured macrophages were less angiogenic than those in 2D culture. Whole-transcriptome sequencing showed that nearly 40% of genes were significantly differently expressed, including nine important angiogenic factors of which seven had been downregulated. In addition, the expression of almost all genes related to two important angiogenic pathways was decreased in 3D-cultured macrophages, including the two key angiogenic factors, VEGFA and ANG2. Together, the findings of our study improve our understanding of angiogenesis and 3D macrophage culture in tissues, and provide new avenues and methods for future research on macrophages.

Robust performance of a novel stool DNA test of methylated SDC2 for colorectal cancer detection: a multicenter clinical study.

BACKGROUND AND AIMS: Stool DNA testing is an emerging and attractive option for colorectal cancer (CRC) screening. We previously evaluated the feasibility of a stool DNA (sDNA) test of methylated SDC2 for CRC detection. The aim of this study was to assess its performance in a multicenter clinical trial setting. METHODS: Each participant was required to undergo a sDNA test and a reference colonoscopy. The sDNA test consists of quantitative assessment of methylation status of SDC2 promoter. Results of real-time quantitative methylation-specific PCR were dichotomized as positive and negative, and the main evaluation indexes were sensitivity, specificity, and kappa value. All sDNA tests were performed and analyzed independently of colonoscopy. RESULTS: Among the 1110 participants from three clinical sites analyzed, 359 and 38 were diagnosed, respectively, with CRC and advanced adenomas by colonoscopy. The sensitivity of the sDNA test was 301/359 (83.8%) for CRC, 16/38 (42.1%) for advanced adenomas, and 134/154 (87.0%) for early stage CRC (stage I-II). Detection rate did not vary significantly according to age, tumor location, differentiation, and TNM stage, except for gender. The follow-up testing of 40 postoperative patients with CRC returned negative results as their tumors had been surgically removed. The specificity of the sDNA test was 699/713 (98.0%), and unrelated cancers and diseases did not seem to interfere with the testing. The kappa value was 0.84, implying an excellent diagnostic consistency between the sDNA test and colonoscopy. CONCLUSION: Noninvasive sDNA test using methylated SDC2 as the exclusive biomarker is a clinically viable and accurate CRC detection method. CHINESE CLINICAL TRIAL REGISTRY: Chi-CTR-TRC-1900026409, retrospectively registered on October 8, 2019; http://www.chictr.org.cn/edit.aspx?pid=43888&htm=4 .

Primary Plasma Cell Leukemia: Real-World Retrospective Study of 46 Patients From a Single-Center Study in China.

BACKGROUND: Primary plasma cell leukemia (PPCL) is a rare and aggressive plasma cell disorder. The use of novel agents, together with autologous stem cell transplantation, has improved survival outcome in PPCL. However, the prognosis is still very poor, and the optimal treatment remains an unmet clinical need. PATIENTS AND METHODS: We studied the efficacy and prognostic impact of novel agents in 46 patients with PPCL patients at the Blood Diseases Hospital in China. We examined the impact of clinical and laboratory features, as well as therapies (bortezomib- and/or immunomodulatory drug-based therapies, chemotherapy) on survival and extent of clinical response, including progression-free survival and overall survival (OS). Progression-free survival and OS were assessed by the Kaplan-Meier method, and survival distributions were compared by log-rank test. RESULTS: In our cohort of 46 PPCL patients, the median age at the time of diagnosis was 54 years. Overall response rate was 54% (25/46). The median (95% confidence interval) progression-free survival time was 6 (0-12.5) months, and OS time was 14 (4.6-23.4) months. The OS time was significantly longer in patients treated with bortezomib-based versus non-bortezomib-based therapies (median [95% confidence interval], 19 [9-28.9] vs. 5 [4-24] months; P = .019). CONCLUSION: This large single-center study of PPCL supports the use of bortezomib-based therapies as frontline treatment in PPCL patients.

Long-term remissions of young patients with high-risk follicular lymphoma after first-line autologous stem cell transplantation: Three case reports.

RATIONALE: Autologous stem cell transplantation (ASCT) is not routinely recommended as first-line choice for follicular lymphoma (FL). However, we actually have observed that young patients with extremely high-risk factors benefit from ASCT. This study aims to speculate the rationality of ASCT as first-line treatment, through 3 cases and review of the literature. PATIENT CONCERNS: 3 young-adult patients with FL received ASCT as first-line treatment. DIAGNOSIS: All the 3 patients were no more than 30 years old and the diagnosis of FL was confirmed by histopathological and immunohistochemical evaluations. They all had multi-organ involvements, and two of them presented with a "leukemic-like" manifestation. Compared with those in the previous literatures, the 3 patients were relatively younger and had more invasive clinical features. INTERVENTIONS: The 3 patients received combined chemotherapy plus rituximab, followed by first-line ASCT. OUTCOMES: All the 3 patients got complete remission and minimal residual disease negativity after ASCT, The median follow-up time was 109 (97-117) months, and all of them were in remission more than 8 years after transplant. LESSONS: Guidelines for FL are mainly based on elderly patients, but are not suitable enough for all, especially for the young FL patients. For young patients with certain high-risk FL, first-line ASCT does not go against the guidelines, and should be recommended individually.