Deciphering the Prognostic Significance of MYD88 and CD79B Mutations in Diffuse Large B-Cell Lymphoma: Insights into Treatment Outcomes.

BACKGROUND: The clinical and genetic characteristics, as well as treatment outcomes, of diffuse large B-cell lymphoma (DLBCL) patients with different MYD88 and CD79B mutation status merit further investigation. OBJECTIVE: This study aims to investigate the distinctions in clinical manifestations, genetic characteristics, and treatment outcomes among MYD88-CD79Bco-mut, MYD88/CD79Bsingle-mut, and MYD88-CD79Bco-wt DLBCL patients. PATIENTS AND METHODS: Clinical and genetic characteristics, along with treatment outcomes among 2696 DLBCL patients bearing MYD88-CD79Bco-mut, MYD88/CD79Bsingle-mut, and MYD88-CD79Bco-wt treated with R-CHOP/R-CHOP-like regimens from the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College and six external cohorts were analyzed. Potential molecular mechanisms were investigated through Gene Set Enrichment Analysis and xCell methodology. RESULTS: In the MCD subtype, patients with MYD88-CD79Bco-mut showed comparable progression-free survival (PFS) and overall survival (OS) compared to MYD88/CD79Bsingle-mut or MYD88-CD79Bco-wt. However, in the non-MCD subtype, patients with MYD88-CD79Bco-mut exhibited significantly inferior OS than MYD88/CD79Bsingle-mut or MYD88-CD79Bco-wt, while there was no significant OS difference between MYD88/CD79Bsingle-mut and MYD88-CD79Bco-wt (median OS: 68.8 [95% CI 22-NA] vs NA [95% CI 112-NA] vs 177.7 [95% CI 159-NA] months; MYD88-CD79Bco-mut vs MYD88/CD79Bsingle-mut: p = 0.02; MYD88-CD79Bco-mut vs MYD88-CD79Bco-wt: p = 0.03; MYD88/CD79Bsingle-mut vs MYD88-CD79Bco-wt: p = 0.33). Regarding patients with MYD88-CD79Bco-mut, there was no significant difference in PFS and OS between the MCD and non-MCD subtypes. Within the MYD88-CD79Bco-mut group, patients with PIM1mut had better PFS than PIM1wt (median PFS: 8.34 [95% CI 5.56-NA] vs 43.8 [95% CI 26.4-NA] months; p = 0.02). Possible mechanisms contributing to the superior PFS of PIM1mut patients may include activated lymphocyte-mediated immunity and interferon response, a higher proportion of natural killer T cells and plasmacytoid dendritic cells, as well as suppressed angiogenesis and epithelial-mesenchymal transition, along with lower fibroblast and stromal score. CONCLUSIONS: In the MCD subtype, patients with MYD88-CD79Bco-mut showed comparable PFS and OS compared to MYD88/CD79Bsingle-mut or MYD88-CD79Bco-wt, while in the non-MCD subtype, they exhibited significantly inferior OS. There was no significant disparity in PFS and OS of MYD88-CD79Bco-mut between the MCD and non-MCD subtypes. The presence of PIM1mut within the MYD88-CD79Bco-mut group correlated with better PFS, which may result from an intricate interplay of immune processes and tumor microenvironment alterations.

Clinical features, prognostic stratification, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma: a multi-institutional real-world study.

The present study aimed to investigate the clinical features, prognosis, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma (ENKTCL). This real-world study retrospectively reviewed 56 newly diagnosed advanced-stage non-nasal type ENKTCL patients from two large-scale Chinese cancer centers in the last 10-15 years and screened 139 newly diagnosed advanced-stage nasal type ENKTCLs admitted during the same period for comparison. The non-nasal type ENKTCLs exhibited significantly higher Ki-67 expression levels compared to nasal type disease (P = 0.011). With a median follow-up duration of 75.03 months, the non-nasal group showed slightly inferior survival outcomes without statistically significant differences compared to the nasal group (median overall survival (OS): 14.57 vs. 21.53 months, 5-year OS: 28.0% vs. 38.5%, P = 0.120). Eastern Cooperative Oncology Group (ECOG) score ≥ 2 (hazard ratio (HR) = 2.18, P = 0.039) and lactic dehydrogenase (LDH) elevation (HR = 2.44, P = 0.012) were significantly correlated with worse OS in the non-nasal group. First-line gemcitabine-based chemotherapy regimens showed a trend toward slightly improved efficacy and survival outcomes compared to non-gemcitabine-based ones in the present cohort of non-nasal ENKTCLs (objective response rate: 91.7% vs. 63.6%, P = 0.144; complete response rate: 50.0% vs. 33.3%, P = 0.502; median progression-free survival: 10.43 vs. 3.40 months, P = 0.106; median OS: 25.13 vs. 9.30 months, P = 0.125), which requires further validation in larger sample size studies. Advanced-stage non-nasal type patients could achieve comparable prognosis with nasal cases after rational therapy. The modified nomogram-revised index (including age, ECOG score, and LDH) and modified international prognostic index (including age, ECOG score, LDH, and number of extranodal involvement) functioned effectively for prognostic stratification in non-nasal type ENKTCLs.

Treatment and prognosis of newly diagnosed advanced-stage extranodal natural killer / T cell lymphoma: a single-center real-world study across two decades.

INTRODUCTION: Although there is now a consensus on asparaginase-based chemotherapy regimens in treatment of advanced-stage extranodal natural killer / T cell lymphomas (ENKTCLs), patient survival in the real-world setting is still not optimistic according to previous literature reports, and the optimal chemotherapeutic regimens and integration of different therapeutic methods under the concept of combined-modality treatment still need to be further explored and verified. METHODS: Newly diagnosed stage Ⅲ / Ⅳ ENKTCL patients from Chinese National Cancer Center in the last two decades were retrospectively collected and analyzed. Overall survival (OS) and progression-free survival (PFS) were determined as primary endpoints. Log-rank tests and Cox proportional hazard models were performed to test for survival differences between subgroups and examine the univariable and multivariable associations. RESULTS: The study included 83 newly diagnosed stage Ⅲ / Ⅳ ENKTCL patients and reported a median OS of 26.07 months and an estimated 5-year OS of 41.3% with a median follow-up of 82.13 months. First-line asparaginase- compared to non-asparaginase-based regimens significantly prolonged PFS (P=0.007; HR=0.48, P=0.020) and showed a tendency to improve OS (P=0.064; HR=0.74, P=0.359). Gemcitabine-based regimens also exhibited a trend towards improved PFS (P=0.048; HR=0.59, P=0.164) and OS (P=0.008; HR=0.67, P=0.282) compared to non-gemcitabine-based ones. The asparaginase and gemcitabine combinations yielded a 5-year OS of 55.0% and led to significantly superior PFS (P=0.020; HR=0.40, P=0.022) and slightly better OS (P=0.054; HR=0.79, P=0.495) compared to the remaining regimens. First-line combined-modality treatment integrating chemotherapy and radiotherapy improved PFS (P=0.051) and OS (P=0.036) compared to chemotherapy alone. Four autologous hematopoietic stem cell transplantation recipients reached a median OS of 58.34 months. CONCLUSION: Asparaginase and gemcitabine alone brought favorable impact on PFS and OS; and the asparaginase and gemcitabine combination chemotherapy yielded the optimal efficacy, response duration and survival outcomes. Combined-modality treatment including potent chemotherapy supplemented by radiotherapy and/or consolidative transplantation could improve prognosis in newly diagnosed advanced-stage ENKTCLs.

Establishment of colloidal gold immunochromatography strip for rapid detection of Karen mikimotoi and its application.

In China, harmful algal blooms (HABs) are one of the most prominent ecological disasters in the coastal areas. Among the harmful algae species that cause HABs, Karen mikimotoi is a kind of algae that appear frequently. It can secrete hemolytic toxins and fish toxins such as glycolipids and unsaturated fatty, posing a significant threat to marine life. In order to establish a fast and effective detection technology for Karen mikimotoi that can be promoted and applied on site, we have developed a test strip which is based on monoclonal antibody technology and the colloidal gold immune-chromatography assay (GICA). The experimental results show that this test strip can detect different growth stages including growth, and stable and recession period of Karen mikimotoi. The detection results can be displayed within 3-15 min. It had high sensitivity and specificity, with a detection limit of 754 cells/mL. A colorimetric card was made to further determine the concentration of algae detected. What is more, we had developed a method that can be used for on-site enrichment of algae cells using a syringe to detect lower concentrations of Karen mikimotoi, with a minimum detection concentration of 100 cells/mL. Also the test strip was used for on-site testing along the coast of China. This test strip not only serves as a warning for the outbreak of red tide, but also provides a new approach for the development of rapid detection technology for red tide algae.

Intensive therapy can improve long-term survival in newly diagnosed, advanced-stage extranodal NK/T-cell lymphoma: A multi-institutional, real-world study.

The study investigated the treatment and prognosis of advanced-stage extranodal natural killer/T-cell lymphoma (ENKTL). With a median follow-up of 75.03 months, the median overall survival (mOS) for the 195 newly diagnosed stage III/IV ENKTL patients was 19.43 months, and estimated 1-, 2-, 3- and 5-year OS were 59.5%, 46.3%, 41.8% and 35.1%, respectively. Chemotherapy (CT) + radiotherapy (RT) compared to CT alone (P = .007), and hematopoietic stem cell transplantation (HSCT) compared to non-HSCT (P < .001), both improved OS. For patients ≤60 years and ineligible for HSCT, other therapies with complete remission led to comparable OS (P = .141). Nine patients ever treated with chidamide achieved a median progression-free survival (mPFS) and mOS of 53.63 (range, 3.47-92.33) and 54.80 (range, 5.50-95.70) months, and four with chidamide maintenance therapy (MT) achieved a mPFS and mOS of 55.83 (range, 53.27-92.33) and 60.65 (range, 53.70-95.70) months, possibly providing an alternative option for non-HSCT patients. Non-anthracycline (ANT)- compared to ANT-, asparaginase (Aspa)- compared to non-Aspa- and gemcitabine (Gem)- compared to non-Gem-based regimens, prolonged PFS (P = .031; P = .005; P = .009) and OS (P = .010; P = .086; P = .003), respectively. Multivariate analysis demonstrated that Gem-based regimens improved PFS (HR = 0.691, P = .061) and OS (HR = 0.624, P = .037). Gem + Aspa combinations slightly improved PFS and OS compared to regimens containing Gem or Aspa alone (P > 0.05). First-line "intensive therapy," including CT (particularly Gem + Aspa regimens), RT, HSCT and alternative chidamide MT, was proposed and could improve long-term survival for advanced-stage ENKTLs. Ongoing prospective clinical studies may shed further light on the value of chidamide MT.

Selection, identification and crystal structure of shark-derived single-domain antibodies against a green fluorescent protein.

Shark variable domain of new antigen receptors (VNARs) are the smallest naturally occurring binding domains with properties of low complexity, small size, cytoplasmic expression, and ease of engineering. Green fluorescent protein (GFP) molecules have been analyzed in conventional microscopy, but their spectral characteristics preclude their use in techniques offering substantially higher resolution. Besides, the GFP molecules can be quenched in acidic environment, which makes it necessary to develop anti-GFP antibody to solve these problems. In view of the diverse applications of GFP and unique physicochemical features of VNAR, the present study aims to generate VNARs against GFP. Here, we identified 36 VNARs targeting eCGP123, an extremely stable GFP, by phage display from three immunized sharks. These VNARs bound to eCGP123 with affinity constant KD values ranging from 6.76 to 605 nM. Among them, two lead VNARs named aGFP-14 and aGFP-15 with nanomolar eCGP123-binding affinity were selected for in-depth characterization. aGFP-14 and aGFP-15 recognized similar epitopes on eCGP123. X-ray crystallography studies clarified the mechanism by which aGFP14 interacts with eCGP123. aGFP-14 also showed cross-reaction with EGFP, with KD values of 47.2 nM. Finally, immunostaining analyses demonstrated that aGFP-14 was able to bind effectively to the EGFP expressed in both cultured cells and mouse brain tissues, and can be used as a fluorescence amplifier for EGFP. Our research demonstrates a feasible idea for the screening and production of shark-derived VNARs. The two high-affinity VNARs developed in the study contribute to the diversity of GFP sdAbs and may enhance the applications of GFP.

Efficacy and safety of PD-1 monoclonal antibody plus rituximab in relapsed/refractory diffuse large B cell lymphoma patients.

BACKGROUND: Patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) have poor outcomes and few treatment options. We report the preliminary results of the efficacy and safety of PD-1 monoclonal antibody (mab) plus Rituximab for r/r DLBCL. METHODS: In this single-center, single-arm phase 2 and retrospective study, r/r DLBCL patients received PD-1 mab and Rituximab every 3 weeks. Immunohistochemistry, fluorescence in situ hybridization, and probe capture-based high-resolution sequencing were performed. Efficacy, safety and prognostic factors were analyzed. RESULTS: Between October 16th, 2018, and July 10th, 2022, 36 patients (10 patients in retrospective study and 26 patients in phase 2 study) were enrolled and received at least one dose of PD-1 mab combined with Rituximab. The objective response rate was 52.8%. The median progression free survival (PFS) and overall survival was 2.8 and 19.6 months, respectively. The median duration of response was 18.7 months. Rare grade 3 or 4 treatment related adverse events were observed. B2M mutations correlated with a significantly poor PFS (p = .013) and OS (p = .009) in DLBCL patients treated with this regimen. CONCLUSION: PD-1 mab combined with Rituximab could be a potential treatment option for r/r DLBCL with manageable safety profile.

MYD88L265P and MYD88other variants show different molecular characteristics and prognostic significance in diffuse large B-cell lymphoma.

PURPOSE: This study aims to investigate the clinical and molecular differences between diffuse large B-cell lymphoma (DLBCL) patients with MYD88L265P and MYD88other. METHODS: DLBCL patients with MYD88 variations were collected from the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CHCAMS), and Suzhou Municipal Hospital from February 6th, 2007 to May 20th, 2022. Clinicopathological parameters and treatment outcomes between MYD88L265P and MYD88other were investigated. RESULTS: A total of 132 patients with MYD88 variations from a cohort of 475 DLBCL patients were included, among which, 78 were MYD88L265P, while 54 were MYD88other. MYD88L265P was more common in non-GCB subtype than MYD88other (83% vs. 60%, P = 0.004). Besides, MYD88L265P was significantly related to higher proportion of testicle/ central nervous system involvement (31% vs. 6%, P < 0.001), PIM1 mutation (71% vs. 39%, P < 0.001), and PIM1 hypermutation (28% vs. 11%, P = 0.018), compared with MYD88other. Compared with MYD88L265P, MYD88other were more likely to have higher percentage of advanced stage (60% vs. 42%, P = 0.044), extranodal site ≥ 2 (45% vs. 28%, P = 0.044), elevated LDH (55% vs. 35%, P = 0.033), positive CD10 expression (36% vs. 16%, P = 0.009), BCL-6 translocation (20% vs. 8%, P = 0.033), and NOTCH pathway gene alteration (24% vs. 13%, P = 0.040). In non-GCB DLBCL subtype, patients with MYD88other were significantly associated with worse progression free survival (PFS) than those with MYD88L265P when treated initially with R-CHOP/R-CHOP-like regimen (P = 0.010). CONCLUSION: The findings of this study indicate that DLBCL patients with MYD88L265P and MYD88other are likely to be two subgroups with different clinical and molecular characteristics. The survival of patients with MYD88other is not superior than those with MYD88L265P, even poorer when focusing on the non-GCB subtype.

The clinical features, treatment, and prognostic factors for peripheral T-cell lymphomas: A single-institution analysis of 240 Chinese patients.

AIM: This study aimed to analyze the clinical features, treatment, survival, and prognostic factors of Chinese patients with peripheral T-cell lymphoma (PTCL) excluding natural killer/T-cell lymphoma (NKTCL). METHODS: Data on patients with newly diagnosed PTCLs between January 1, 2006 and December 31, 2017 at our hospital were retrospectively reviewed. Patients with NKTCL were excluded. RESULTS: A total of 240 patients were included. PTCL, not otherwise specified (PTCL-NOS), was the most frequent subtype (42.5%), followed by angioimmunoblastic T-cell lymphoma (AITL) (21.3%), anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALK-ALCL) (16.7%), ALK-positive ALCL (ALK+ALCL) (10.8%) and others (8.8%). With a median follow-up of 81.1 months, the 5-year progression-free survival (PFS) and overall survival (OS) rates for all patients were 30.4% (95% CI 25.0%-37.0%) and 48.8% (95% CI 42.6%-55.7%), respectively. On multivariate analysis, no consolidative autologous stem cell transplantation (ASCT) and not achieving complete response after first-line chemotherapy retained independently prognostic value for inferior PFS and OS. Besides, bone marrow involvement and serum albumin level were independent factors for PFS, and Eastern Cooperative Oncology Group performance status ≥2 was significantly predictive of inferior OS. Compared with PTCL-NOS, significantly superior PFS and OS were observed for ALK+ALCL and ALK-ALCL. CONCLUSION: The survival outcomes with current treatment for most PTCL subtypes are still unsatisfactory. Prospective randomized studies are needed to establish the value of consolidative ASCT in PTCL, and novel therapeutic approaches should be explored.

Genetic Profiling of Diffuse Large B-Cell Lymphoma: A Comparison Between Double-Expressor Lymphoma and Non-Double-Expressor Lymphoma.

INTRODUCTION: Data are limited regarding the genetic profiling of diffuse large B-cell lymphoma (DLBCL) with double expression of MYC and BCL2 proteins without underlying rearrangements (double-expressor lymphoma [DEL]). This study aimed to describe the genetic profiling and determine the prognostic significance in patients with DEL and in those with non-DEL. METHODS: Capture-based targeted sequencing was performed on 244 patients with de novo DLBCL, not otherwise specified. Immunohistochemistry staining was performed for evaluating the MYC and BCL2 expression. RESULTS: Among 244 patients, 46 patients had DEL, and 198 had non-DEL. KMT2D, CD58, EP300, PRDM1, TNFAIP3 and BCL2 gain or amplification (BCL2GA/AMP) were significantly more frequently altered in the DEL group. Alterations in the BCR/TLR (p = 0.021), B-cell development and differentiation (p = 0.004), and NF-κB (p = 0.034) pathways occurred more frequently in patients with DEL. Thirty-seven DEL patients and 132 non-DEL patients were included for survival analyses. DEL was not significantly associated with progression-free survival (PFS) (p = 0.60) and overall survival (OS) (p = 0.49). In DEL patients, after adjusting for the International Prognostic Index, BCL2 alteration (HR 2.516, 95% CI 1.027-6.161; p = 0.044) remained an independent predictor of inferior PFS. BCL2GA/AMP also predicted poor PFS, but with marginal statistical significance (HR 2.489, 95% CI 0.995-6.224; p = 0.051). CONCLUSION: There was difference in profiling of altered genes and signaling pathways between the DEL group and the non-DEL group. The presence of DEL alone should not be considered as an adverse prognostic indicator, and BCL2 alteration could define a subset of patients with poor prognosis within DEL.

Clinical characteristics and treatment outcomes of Chinese diffuse large B-cell lymphoma patients in the era of rituximab (2005-2018).

Background: Rituximab combined with cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP) regimen has improved the survival of diffuse large B-cell lymphoma (DLBCL) patients worldwide, compared with CHOP alone. Several limitations were seen in previous studies of Chinese DLBCL patients treated with R-CHOP or R-CHOP-like regimens. This study aimed to investigate the clinical characteristics and treatment outcomes of Chinese DLBCL patients treated with the standard first-line treatment. Methods: Clinical data were collected from DLBCL patients who received frontline R-CHOP or R-CHOP-like regimens at the Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College (CHCAMS) between January 1, 2005, and December 31, 2018. The treatment outcomes were compared with those of patients diagnosed with DLBCL between 2004 and 2017 and who received immunochemotherapy from the United States Surveillance, Epidemiology, and End Results (SEER) database. Survival rates were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis of progression-free survival (PFS) and overall survival (OS) was performed using Cox proportional hazard regression. Results: Overall, 1084 patients from the CHCAMS and 4013 patients from the SEER database were included in the study. As of April 30, 2022, the median follow-up period for the CHCAMS group was 87.3 (range: 0.5-195.4) months. For the CHCAMS group, the 5-year PFS and OS rates were 61.7% (95% confidence interval [CI]: 58.8-64.7%) and 70.6% (95% CI: 67.8-73.4%), respectively. For the SEER group, the 5-year OS rate was 66.5% (95% CI: 65.0-68.0%), which was inferior to that of the CHCAMS group (P â€‹< â€‹0.001). After adjusting for clinical factors and treatment, no significant difference was observed in the OS between the CHCAMS and SEER groups (P â€‹= â€‹0.867). In the CHCAMS group, multivariate analysis showed that an Eastern Cooperative Oncology Group performance status score ≥2, presence of B symptoms, Ann Arbor stage III-IV, elevated serum ß2-microglobulin levels, and bulky mass were independent adverse prognostic factors affecting PFS and OS (P â€‹< â€‹0.05). Additionally, patients aged over 60 years, elevated lactate dehydrogenase levels, and more than two extranodal sites were independent adverse prognostic factors for OS (P â€‹< â€‹0.05). Local radiotherapy was significantly associated with better PFS (P â€‹< â€‹0.001) and OS (P â€‹= â€‹0.001). Conclusion: After adjusting for clinical and treatment-related factors, no significant difference was observed in the 5-year OS rate between Chinese DLBCL patients treated with standard first-line treatment and those from the SEER database.

Development of a test strip for rapid detection of Gymnodinium catenatum.

Harmful algal blooms (HABs) are major ecological and environmental problems in China's coastal waters and seriously threaten the stability of the marine ecosystem and human health. Gymnodinium catenatum is a toxic red tide dinoflagellate. It can produce paralytic shellfish toxins (PSP), which cause serious hazards to marine organisms, public health, and safety. In this paper, a test strip based on colloidal gold immunochromatography (GICG) was developed for the rapid detection of Gymnodinium catenatum. The experimental results showed that the test strip has good specificity and sensitivity. It not only detects the different components of Gymnodinium catenatum but also may detect algal toxins. The lowest density of Gymnodinium catenatum that can be detected by this test strip is approximately 120 cells/mL. Cross-reaction indicated that the test strip had a high specificity for Gymnodinium catenatum. This test strip provides a rapid method for in situ detection of Gymnodinium catenatum and a reference method for the monitoring of other harmful algae to serve as an early warning of upcoming red tides. It also provides a new way to prepare more detection methods for toxic algal toxins.

Enhancement of the International prognostic index with ß2-microglobulin, platelet count and red blood cell distribution width: a new prognostic model for diffuse large B-cell lymphoma in the rituximab era.

BACKGROUND: This study aimed to propose a new user-friendly, cost effective and robust risk model to facilitate risk stratification for diffuse large B-cell lymphoma (DLBCL) treated with frontline R-CHOP regimens. METHODS: Data on 998 patients with de novo DLBCL diagnosed between Jan 1st, 2005 and Dec 31st, 2018 at our center, who received frontline R-CHOP or R-CHOP-like regimens, were retrospectively collected. Patients were randomly divided into the training cohort (n = 701) and the validation cohort (n = 297). A new prognostic model for overall survival (OS) was built based on the training cohort. The performance of the new model was compared with International prognostic index (IPI), revised IPI (R-IPI) and National Comprehensive Cancer Network (NCCN)-IPI (NCCN-IPI). The new model was validated in the validation cohort. RESULTS: The multivariate analysis of the training cohort showed that the IPI, ß2-microglobulin, platelet count and red blood cell distribution width were independent factors for OS, which were incorporated into the new prognostic model. Patients were stratified into low risk, low-intermediate risk, high-intermediate risk, high risk and very high risk groups, with distinct survival outcomes. The new model achieved good C-indexes for 5-year OS prediction of 0.750 (95%CI 0.719-0.781) and 0.733 (95%CI 0.682-0.784) in the training and validation cohorts, respectively, and displayed well-fitted calibration curves. The C-index and the time-dependent ROC analysis demonstrated better performance of the new model than the IPI, R-IPI and NCCN-IPI in both training and validation cohorts. The integrated Brier score for predicting 5-year OS of the new model was lower than that of the IPI, R-IPI and NCCN-IPI in both cohorts, and decision curve analysis also showed a higher net benefit, indicating the superiority of the new model over the conventional models. CONCLUSION: The new prognostic model might be a useful predictive tool for DLBCL treated with R-CHOP regimens. Further external validation is warranted.

GMLight: Lighting Estimation via Geometric Distribution Approximation.

Inferring the scene illumination from a single image is an essential yet challenging task in computer vision and computer graphics. Existing works estimate lighting by regressing representative illumination parameters or generating illumination maps directly. However, these methods often suffer from poor accuracy and generalization. This paper presents Geometric Mover's Light (GMLight), a lighting estimation framework that employs a regression network and a generative projector for effective illumination estimation. We parameterize illumination scenes in terms of the geometric light distribution, light intensity, ambient term, and auxiliary depth, which can be estimated by a regression network. Inspired by the earth mover's distance, we design a novel geometric mover's loss to guide the accurate regression of light distribution parameters. With the estimated light parameters, the generative projector synthesizes panoramic illumination maps with realistic appearance and high-frequency details. Extensive experiments show that GMLight achieves accurate illumination estimation and superior fidelity in relighting for 3D object insertion. The codes are available at https://github.com/fnzhan/Illumination-Estimation.

A new prognostic model including platelet/lymphocyte ratio and International Prognostic Score 3 for freedom from progression in patients with previously untreated advanced classical Hodgkin lymphoma.

PURPOSE: We aimed to develop a new risk stratification tool to predict freedom from progression (FFP) for newly diagnosed advanced classical Hodgkin lymphoma (cHL). METHODS: We collected data from 386 patients with advanced cHL diagnosed between December 8, 2000 and October 29, 2018, and treated with curative intent with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or an ABVD-equivalent regimen. Cases were randomly divided into training and validation cohorts at a ratio of 7:3. The new model was constructed based on the results of Cox proportional hazards model in the training cohort. Comparisons of discrimination between the new model and other models in the training and validation cohorts for FFP prediction were measured by time-dependent area under curve (tAUC) and Harrell's C-index. Calibration plots were constructed to compare the consistency between the predicted and observed estimates of survival probability for the new model in the training and validation cohorts. RESULTS: The new model (IPSPLR) composed of International Prognostic Score (IPS)-3 and platelet/lymphocyte ratio (PLR) provided four distinct risk groups. The IPSPLR showed better discriminative ability when compared with IPS-3 and IPS-7. The AUC of IPSPLR was consistently higher than that of IPS-3 and IPS-7 between 12 and 120 months. The C-index of the IPSPLR was higher than that of IPS-7 and IPS-3. The calibration plots showed an excellent agreement between the IPSPLR-predicted and observed estimates of 5-year FFP. CONCLUSION: The IPSPLR is an easily used tool for FFP prediction for newly diagnosed advanced cHL. Validation of this tool in other large datasets is needed.

Prognostic role of red blood cell distribution width and platelet/lymphocyte ratio in early-stage classical Hodgkin lymphoma.

Background: To investigate the prognostic role of red blood cell distribution width (RDW) and platelet/lymphocyte ratio (PLR) in early-stage classical Hodgkin lymphoma (cHL). Materials & methods: Data from 402 patients with newly diagnosed early-stage cHL were retrospectively collected. The impact of factors on complete response (CR) rate and freedom from progression (FFP) was analyzed. Results: High PLR was associated with lower CR, but high RDW was not. The univariate analysis showed that RDW and PLR were predictive of FFP. On multivariate analysis, high PLR was an independent risk factor for inferior FFP. Subgroup analysis and a prognostic model for FFP based on PLR validated the prognostic role of PLR. Conclusion: PLR was a robust prognostic factor for newly diagnosed early-stage cHL.

A prognostic nomogram constructed for relapsed or refractory diffuse large B-cell lymphoma patients.

AIM: The clinical course of diffuse large B-cell lymphoma (DLBCL) is variable and there is a lack of prognostic markers and models for relapsed or refractory (r/r) DLBCL. Hence, we conducted this study to identify independent factors that can predict the survival rate of r/r DLBCL patients. METHODS: A total of 416 r/r DLBCL patients who were pretreated with first-line anthracycline-based chemotherapy at the National Cancer Center in China between 2006 and 2016 were divided into the primary (n = 291) and validation (n = 125) cohorts. The effect of preclinical and clinical indicators on DLBCL survival rates of the two cohorts were evaluated by univariate and multivariate analyses. Factors showing good correlation with patient survival rates were used to construct a prognostic nomogram. RESULTS: Multivariate analysis of the primary cohort revealed five independent prognostic factors: lactate dehydrogenase level at diagnosis, response to front line treatment, progression/recurrence pattern, location, and invasion on progression/recurrence, which were then used to construct a nomogram. The nomogram was shown to have a C-index of 0.76 and AUC values of 0.81 and 0.80 for the primary and validation cohorts, respectively, suggesting good prognostic power. We further stratified the r/r DLBCL patients into four risk groups according to the newly developed nomogram. CONCLUSION: The prognostic nomogram constructed using the five identified clinical indicators can potentially be applied in the clinical setting to guide treatment decision.

Dismal outcome of relapsed or primary refractory adult T-cell lymphoblastic lymphoma: A retrospective study from China.

AIM: Little is known about the outcome and prognostic factors of relapsed or refractory T-cell lymphoblastic lymphoma (T-LBL), especially in adult patients. The aim of this study was to analyze the characteristics, outcome and prognostic factors for this patient population. METHODS: Between January 2006 and December 2017, we retrospectively analyzed 84 adult patients with T-LBL, and 44 relapsed or primary refractory patients were included in this analysis. Clinical features, treatment and follow-up information were collected. RESULTS: For all 44 patients, the median time to disease progression or relapse was 9.5 months after diagnosis. At a median follow-up of 19.6 months, 40 (90.9%) patients died. The 3- and 5-year overall survival (OS) rates after disease progression or relapse were 7.8% and 5.2%, respectively. Among 30 patients who had detailed information of second-line treatment, only eight achieved a second complete remission (CR). Two of these eight patients subsequently underwent autologous or allogeneic stem cell transplantation (SCT), of whom one died from disease progression after autologous SCT, and one was free of event at 84 months after allogeneic SCT. Three of the rest six patients in second CR were still alive after chemotherapy alone. All the remaining patients who failed to gain second CR eventually died. In univariate analysis, only the achievement of second CR was positively predictive of OS (hazard ratio (HR) = 0.307; 95% confidence interval (CI), 0.104-0.905; P = 0.032). CONCLUSION: The outcome of adult patients with relapsed or refractory T-LBL is extremely dismal. Patients with relapsed or refractory T-LBL should be encouraged to participate in clinical trials where novel therapeutic approaches are available.

Prognostic value of BCL2 and TP53 genetic alterations for diffuse large B-cell lymphoma patients treated with R-CHOP.

OBJECTIVE: Limited data about the prognostic significance of BCL2 mutations and BCL2 copy number variations in diffuse large B-cell lymphoma (DLBCL) are available. This study aimed to comprehensively describe BCL2 genetic alterations in DLBCL patients, and examine correlation of BCL2, TP53 and other genetic alterations with outcomes in patients treated with R-CHOP. METHODS: Probe capture-based high-resolution sequencing was performed on 191 patients diagnosed with de novo DLBCL. MYC, BCL2, and BCL6 protein expressions were detected by immunohistochemistry. RESULTS: The presence of BCL2 alterations significantly correlated with poor progression-free survival (PFS) (5-year PFS: 13.7% vs. 40.8%; P = 0.003) and overall survival (OS) (5-year OS: 34.0% vs. 70.9%; P = 0.036). Importantly, patients who harbored BCL2 gain/amplifications (BCL2GA/AMP) also had a remarkably inferior 5-year PFS (11.1% vs. 38.3%; P < 0.001) and OS (22.1% vs. 69.6%; P = 0.009). In contrast, neither BCL2 mutations nor BCL2 translocations were significantly prognostic for survival. Multivariable analyses showed that the presence of BCL2 alterations, especially BCL2GA/AMP, TP53 mutations, and International Prognostic Index (IPI) were significantly associated with inferior PFS and OS. Novel prognostic models for OS were constructed based on 3 risk factors, including BCL2 alterations (Model 1) or BCL2GA/AMP (Model 2), TP53 mutations, and IPI, to stratify patients into 4 risk groups with different survival outcomes. CONCLUSIONS: This study showed that DLBCL patients treated with R-CHOP, BCL2 alterations, especially BCL2GA/AMP and TP53 mutations were significantly associated with inferior outcomes, which were independent of the IPI. The novel prognostic models we proposed predicted outcomes for DLBCL patients treated with R-CHOP, but further validation of the prognostic models is still warranted.

The pretreatment platelet count predicts survival outcomes of diffuse large B-cell lymphoma: An analysis of 1007 patients in the rituximab era.

BACKGROUND: The prognostic value of platelet count in diffuse large B-cell lymphoma (DLBCL) has not been extensively investigated. We aimed to examine the association of pretreatment platelet count with disease features, and further examine the prognostic significance of platelet count in DLBCL treated with the R-CHOP regimen. METHODS: Patients with DLBCL diagnosed between Jan 1 st, 2005 and Dec 31 st, 2018 at Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. Propensity score matching (PSM) was used to balance confounding factors. RESULTS: A total of 1007 eligible patients who received frontline R-CHOP or R-CHOP-like regimens were included in this study. The optimal cutoff value of platelet count was 157 × 109/L, as determined by the Maximally Selected Rank Statistics method. Patients with the platelet count ≤157 × 109/L had significantly inferior overall survival (OS) (5-year OS, 44.4 % vs. 74.9 %, P < 0.001) and progression-free survival (PFS) (5-year PFS, 35.5 % vs. 65.9 %, P < 0.001) than those with the platelet count >157×109/L. Multivariate analyses showed that pretreatment platelet count ≤ 157 × 109/L was an adversely independent prognostic factor for OS (hazard ratio [HR] 1.960, 95 % confidence interval [CI] 1.418-2.709, P<0.001) and PFS (HR 1.443, 95 %CI 1.080-1.927, P = 0.013). The PSM analysis and subgroup analyses further confirmed the significantly negative impact of low platelet count on OS and PFS. CONCLUSION: The pretreatment platelet count may be a simple, cost-effective and useful prognostic factor in DLBCL patients treated with frontline R-CHOP regimens. Further investigation is warranted to elucidate the biologic mechanism underlying the prognostic significance of platelet count in DLBCL.