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Volatile products from thermal decomposition of lignocellulosic biomass have been well characterized, but the solid- and liquid-phase reactions during the early stages of decomposition are largely unknown. Here the initial solid-phase biomass thermal deconstruction reactions were analyzed in situ and with high particle heating rates, delineating how these processes occur. A variety of instrumentation was used to quantify the extent and relative rates of deconstruction, demonstrating that biopolymers resist the thermally energetic conditions to differing degrees, even when ensconced in biomass cell walls. Hemicellulose and the more frangible lignin components decompose and volatilize more readily than cellulose, which temporarily enriches biomass with cellulose. These chemical changes manifest in larger cell wall structural and mechanical property transformations. In all, this investigation concludes that these solid-phase reactions strongly influence the production rates of volatile species and will require additional study before these processes can be modeled precisely to improve yields of desired product.

Abstract Background It is unknown whether serum procalcitonin (PCT) concentration monitoring can differentiate between bacterial infection or cytokine release syndrome (CRS) when chimeric antigen receptor T‐cell (CAR‐T) recipients present with a constellation of signs and symptoms that may represent both complications. Objective The objective of the study was to assess the utility of serum PCT concentrations as a biomarker of bacterial infection in CAR‐T recipients. Study design This single‐center, retrospective, medical record review evaluated patients prescribed CAR‐T therapy until death or 30 days after infusion. Logistic regression modeling determined the association between elevated serum PCT concentrations within 48 h of fever onset and microbiologically confirmed infection. Secondary outcomes included clinically suspected infection, CAR‐T toxicity rates, and broad‐spectrum antibiotic usage. Predictive performance of PCT was assessed by area under the receiver operating characteristic curve (AUC). Results The 98 included patients were a median age of 63 (IQR: 55–69) years old, 47 (48%) were male, and 87 (89%) were Caucasian. Baseline demographics and clinical characteristics were similar between patients with and without a bacterial infection. Serum PCT >0.4 ng/mL within 48 h of fever was significantly associated with a microbiologically confirmed bacterial infection (OR: 2.75 [95% CI: 1.02–7.39], p = 0.045). Median PCT values in patients with and without confirmed infections were 0.40 ng/mL (IQR: 0.26, 0.74) and 0.26 ng/mL (IQR: 0.13, 0.47), respectively. The AUC for PCT to predict bacterial infection was 0.62 (95% CI 0.48–0.76). All patients experienced CRS of some grade, with no difference in CRS severity based on elevated PCT. Broad‐spectrum antibiotics were used for a median of 45% and 23% of days in those with and without confirmed infection, respectively (p = 0.075). Conclusion Elevated serum PCT concentrations above 0.4 ng/mL at time of first fever after CAR‐T infusion was significantly associated with confirmed bacterial infection. Furthermore, rigorous, prospective studies should validate our findings and evaluate serial PCT measurements to optimize antimicrobial use after CAR‐T therapy.

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the management of aggressive hematologic malignancies. However, its role in patients with lymphoma and cardiac metastasis or cardiomyopathy remains undefined due to potentially life-threatening complications such as ventricular rupture, cardiac tamponade, and circulatory failure. We present a case series of patients with lymphoma and cardiomyopathy or cardiac metastasis managed with chimeric antigen receptor T-cell therapy. (Level of Difficulty: Advanced.)

Abstract Our phase III trial reported that autograft‐absolute lymphocyte count (A‐ALC) improved survival post‐autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) for a short‐term follow‐up of 2 years. We evaluated retrospectively in our phase III trial patients that the A‐ALC still confers survival benefit with a longer follow‐up. With a median follow‐up of 127.6 months, patients infused with an A‐ALC ≥ 0.5 × 109 cells/kg experienced better overall survival (HR = 0.392, 95% confidence of interval [CI]: 0.224–0.687, p

Abstract Background F-18 fluorodeoxyglucose positron emission tomography computed tomography (PET/CT) is used to assess response of non-Hodgkin lymphoma (NHL) to chimeric antigen receptor T cell (CAR-T) therapy. We sought to describe metabolic and volumetric PET prognostic factors at one month post-CAR-T and identify which patients with partial response (PR) or stable disease (SD) are most likely to subsequently achieve complete response (CR), and which will develop progressive disease (PD) and death. Methods Sixty-nine patients with NHL received axicabtagene ciloleucel CAR-T therapy. One-month post-CAR-T infusion and PET/CT scans were segmented with a fixed absolute SUV maximum (SUVMax) threshold of 2.5 using a semiautomated workflow with manual modification to exclude physiologic uptake as needed. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUVMax, and other lesion characteristics were calculated and associated with risk of PD and death. Results Patients with total MTV > 180 cc, presence of bone or parenchymal disease, SUVMax > 10, single lesion TLG > 245 g, or > 2 total lesions had increased risk of death. Patients with total MTV > 55 cc, total TLG > 250 cc, SUV Max > 10, or > 2 total lesions had increased risk of PD. For the subset of 28 patients with PR/SD, higher SUVMax was associated with increased risk of subsequent PD and death. While 86% of patients who had SUVMax ≥ 10 eventually had PD (HR 3.63, 1.13–11.66, p = 0.03), only 36% of those with SUVMax

Abstract Diffuse large B-cell lymphoma (DLBCL), either concurrent with or transformed from follicular lymphoma (FL) is often excluded from clinical trials. Lenalidomide has response rates of 45% in relapsed transformed DLBCL. Herein we present an analysis of MC078E, a phase II clinical trial testing lenalidomide plus R-CHOP (R2CHOP) for patients with untreated transformed/concurrent DLBCL (NCT00670358). Adult patients with transformed or concurrent DLBCL were included. Patients received six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) with lenalidomide 25 mg days 1–10 of each cycle. The primary outcome was progression-free survival (PFS) at 24 months. Secondary outcomes were response rates, event-free survival (EFS), and overall survival (OS). Thirty-nine patients were accrued from August 5, 2013 to July 28, 2020 and 33 were eligible by central pathology review. The median age was 64 (24–80) years, 18 (54%) were male, 25 (76%) were concurrent and 8 (24%) were transformed DLBCL. The PFS, EFS, and OS rates at 24 months were 84.4% (CI95: 67.2–94.7%), 84.5% (CI95: 72.9–98%), and 97.0% (CI95: 91.3–100%), respectively. R2CHOP is effective in concurrent and transformed DLBCL. The study supports the inclusion of anthracycline-naive transformed and concurrent DLBCL in future clinical trials of novel immunomodulatory analogues.

Abstract Magnesium is an essential element that is involved in critical metabolic pathways. A diet deficient in magnesium is associated with an increased risk of developing cancer. Few studies have reported whether a serum magnesium level below the reference range (RR) is associated with prognosis in patients with diffuse large B cell lymphoma (DLBCL). Using a retrospective approach in DLBCL patients undergoing autologous stem cell transplant (AHSCT), we evaluated the association of hypomagnesemia with survival. Totally, 581 patients eligible for AHSCT with a serum magnesium level during the immediate pre-transplant period were identified and 14.1% (82/581) had hypomagnesemia. Hypomagnesemia was associated with an inferior event-free (EFS) and overall survival (OS) compared to patients with a serum magnesium level within RR; median EFS: 3.9 years (95% CI: 1.63–8.98 years) versus 6.29 years (95% CI: 4.73–8.95 years) with HR 1.63 (95% CI: 1.09–2.43, p = 0.017) for EFS, and median OS: 7.3 years (95% CI: 2.91—upper limit not estimable) versus 9.7 years (95% CI: 6.92–12.3 years) with HR 1.90 (95% CI: 1.22–2.96, p = 0.005) for OS months 0–12, respectively. These findings suggest a potentially actionable prognostic factor for patients with DLBCL undergoing AHSCT.

Abstract Background Belinostat is a histone deacetylase inhibitor approved for relapsed refractory peripheral T-cell lymphoma (PTCL). The primary objective of this study was to determine the maximum tolerated dose (MTD) of belinostat combined with CHOP (Bel-CHOP). Secondary objectives included safety/tolerability, overall response rate (ORR), and belinostat pharmacokinetics (PK). Methods Patients were ≥ 18 years with histologically confirmed, previously untreated PTCL. Patients received belinostat (1000 mg/m2 once daily) + standard CHOP for 6 cycles with varying schedules using a 3 + 3 design in Part A. Part B enrolled patients at MTD dose. Results Twenty-three patients were treated. One patient experienced DLT (Grade 3 non-hematologic toxicity) on Day 1–3 schedule, resulting in escalation to Day 1–5 schedule (n = 3). No DLTs were observed and Day 1–5 schedule with 1000 mg/m2 was declared as MTD. Twelve additional patients were enrolled in Part B using MTD. Median relative dose intensity was 98%. All patients experienced adverse events (AEs), including nausea (78%), fatigue (61%), and vomiting (57%). Serious AEs occurred in 43%, with febrile neutropenia (17%) and pyrexia (13%). Overall ORR was 86% with 71% reported CR at MTD. Belinostat PK parameters were similar to single-agent. Conclusions Bel-CHOP was well tolerated and MTD in CHOP combination was the same dose and schedule as single agent dosing. Trial Registration: ClinicalTrials.gov Identifier: NCT01839097.

The prognosis of relapsed/refractory (R/R) primary central nervous system lymphoma (PCNSL) is dismal, and there are limited treatment options for these patients. This was a prospective single-arm phase II study of combined pemetrexed and lenalidomide for salvage treatment of R/R PCNSL. Patients with R/R PCNSL (n = 38) who had undergone two or more different therapeutic regimens and experienced disease progression or recurrence were enrolled. The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Patients were followed up for a median of 18 (range, 1–36) months. ORR was 68.4%, with median PFS and OS of 6 and 18 months, respectively. Adverse events (AEs) included myelosuppression, fatigue, nausea, fever, infection, cardiac disease, and thrombogenesis. Commonly observed grade ≥ 3 AEs included neutropenia (5.3%), leukopenia (2.6%), thrombocytopenia (7.9%), and infection (2.6%). Elevated lactate dehydrogenase (LDH) levels (χ2 = 13.25; P = 0.0003) and bulky disease (P = 0.032; χ2 = 4.580) were associated with short PFS. Elevated serum LDH level (P = 0.011; χ2 = 6.560), abnormal lymphoma cells in the cerebrospinal fluid (CSF) [P = 0.011; χ2 = 6.445], and multiple lesions (P = 0.036; χ2 = 4.404) were significantly associated with poorer OS. Abnormal lymphoma cells in the CSF were an independent predictor of poor prognosis on multivariate analysis (P = 0.034; hazard ratio (HR) = 2.836; 95% confidence interval, 1.082–7.434). Our results indicate that pemetrexed plus lenalidomide is effective for heavily treated R/R PCNSL, with moderate toxicity. Trial registration: #ChiCTR1900028070.

Predictive coding theories of perception highlight the importance of constantly updated internal models of the world to predict future sensory inputs. Importantly, such theories suggest that prediction-error signalling should be specific to the violation of predictions concerning distinct attributes of the same stimulus. To interrogate this as yet untested prediction, we focused on two different aspects of face perception (identity and orientation) and investigated whether cortical regions which process particular stimulus attributes also signal prediction violations with respect to those same stimulus attributes. We employed a paradigm using sequential trajectories of images to create perceptual expectations about face orientation and identity, and then parametrically violated each attribute. Using MEG data, we identified double dissociations of expectancy violations in the dorsal and ventral visual streams, such that the right fusiform gyrus showed greater prediction-error signals to identity violations than to orientation violations, whereas the left angular gyrus showed the converse pattern of results. Our results suggest that perceptual prediction-error signalling is directly linked to regions associated with the processing of different stimulus properties.

Abstract Background To describe the recent diagnostic and treatment options for the most predominant form of primary vitreoretinal lymphoma (PVRL), namely diffuse large B cell lymphoma. This is mainly based on the experience at the Mayo Clinic as well as a partial review of the literature. MYD88 L265P mutation is seen in about 80% of cases; therefore, a polymerase chain reaction for this mutation helps in making the diagnosis that has been notoriously difficult to make. Local therapy using intravitreal methotrexate and rituximab has been very helpful in the treatment of the local disease. Systemic high-dose intravenous methotrexate is helpful in treating bilateral disease in conjunction with intravitreal therapy. Whether it is helpful in preventing or delaying the development of central nervous system lymphoma (CNSL) is still in dispute. If there is development of CNSL or recurrent ocular disease, alternatives to high-dose methotrexate under investigation include pomalidomide, stem cell transplantation, or ibrutinib, with or without local therapy. Vitrectomy alone might be helpful as a debulking procedure. Because of the risks of redevelopment of disease, local radiation should be given if other options are not possible. Aqueous levels of IL10 are helpful in following the redevelopment of local disease. Conclusion Although PVRL is still a difficult disease to diagnose and treat, new advances are helping to make these easier. Larger collaborative studies will be helpful in determining better treatments.

Abstract Background The current standard of care for classical Hodgkin lymphoma (HL) is multiagent chemotherapy with or without radiation. In patients who relapse or fail to respond, additional high-dose chemotherapy with autologous hematopoietic stem cell transplantation (AHSCT) can improve progression-free survival (PFS). Novel therapies are required for patients refractory to chemotherapy and AHSCT. The mammalian target of rapamycin inhibitor everolimus has shown preliminary activity in preclinical models of HL and promising efficacy in patients with relapsed or refractory HL. Methods This was an open-label, two-stage, phase 2 study that enrolled 57 patients aged ≥ 18 years with classic HL that had progressed after standard therapy. Patients received everolimus 10 mg daily until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision. The primary endpoint was overall response rate; secondary endpoints included PFS, overall survival, time to response, duration of response, and safety. Results Overall response rate was 45.6% (95% confidence interval [CI] 32.4–59.3%); five patients (8.8%) experienced a complete response and 21 patients had a partial response (36.8%). Median PFS was 8.0 months (95% CI 5.1–11.0 months). Seven patients (12%) were long-term responders (≥ 12 months). The most common study drug-related adverse events were thrombocytopenia (45.6%), fatigue (31.6%), anemia (26.3%), rash (24.6%), and stomatitis (22.8%). Conclusions Everolimus 10 mg/day demonstrated favorable results in patients with heavily pretreated, relapsed, or refractory classical HL. These findings support the further evaluation of everolimus in this indication. Trial registration ClinicalTrials.gov NCT01022996. Registered November 25, 2009

Tumour expression profiling is currently used for prognostic and predictive purposes without taking into account the intra patient heterogeneity. Here the authors show that cancer cell specific signatures overcome the tumour heterogeneity effect and result in better classification of colorectal cancer patients.

Abstract Background To determine the occurrence of macular edema (ME) in vitreoretinal lymphoma (VRL). Methods Retrospective analysis of 17 patients (31 eyes) with VRL. A review of the literature was done as well. Results Nine patients (15 eyes) had fluorescein angiography and/or optical coherence tomography at presentation. In the ME group (six eyes of four patients), three patients (five eyes) had prior chemotherapy and radiation. Excluding eyes with radiation retinopathy (three eyes), rate of ME was 25% (3/12). When two unirradiated fellow eyes of eyes with radiation retinopathy were also excluded, ME rate was 10% (1/10). Excluding the eyes with intraocular surgery, the rate of ME was 0%. In the group without ME (nine eyes of six patients), one patient (one eye) was treated with chemotherapy and radiation and three patients (five eyes) with chemotherapy. Review of the literature showed that the ME was found between 2 and 60% of cases, but most of the cases with ME had prior interventions. Conclusions Macular edema in VRL is not uncommon but usually related to prior interventions. Macular edema as an initial presentation of VRL is rare.