Descriptive epidemiological information on myeloproliferative neoplasms (MPNs) and myelodysplastic (MDS)/MPNs is largely derived from single institution and European population‐based studies. Data ...obtained following adoption of the World Health Organization classification of haematopoietic neoplasms and JAK2 V617F mutation testing are sparse. Using population‐based data, we comprehensively assessed subtype‐specific MPN and MDS/MPN incidence rates (IRs), IR ratios (IRRs) and relative survival (RS) in the United States (2001–12). IRs were highest for polycythaemia vera (PV) (IR = 10·9) and essential thrombocythaemia (ET) (IR = 9·6). Except for ET and mastocytosis, overall IRs were significantly higher among males (IRRs = 1·4–2·3). All evaluable MPNs were associated with lower IRs among Hispanic whites than non‐Hispanic whites (NHWs), with the exception of BCR‐ABL1‐positive chronic myeloid leukaemia (CML), chronic eosinophilic leukaemia (CEL) and juvenile myelomonocytic leukaemia. Except for CEL, Asians/Pacific Islanders had significantly lower MPN IRs than NHWs. ET, MPN‐unclassifiable and CEL IRs were 18%, 19% and 60% higher, respectively, among blacks than NHWs. Five‐year RS was more favourable for younger (<60 years) than older individuals and for women compared with men, except for PV at older ages. RS was highest (>90%) for younger PV and ET patients and lowest (<20%) for older chronic myelomonocytic leukaemia and atypical BCR‐ABL1‐negative CML patients. Varying MPN and MDS/MPN incidence patterns by subtype support distinct aetiologies and/or susceptible populations. Decreased survival rates as compared to that expected in the general population were associated with every MPN subtype, highlighting the need for new treatments, particularly among older individuals.
For the improvement of daily needs, the use of many chemicals is growing rapidly. Some of these compounds are harmful to human health. Moreover, due to the wide range of applications in industry, it ...has become necessary to develop rapid and accurate detectors for chemical compounds. Herein, a new chemical photonic structure is theoretically investigated as a detector for isopropanol, ethanol, and acetone. The proposed sensor is based on a 1D ternary photonic crystal and has the structure (Si/Si3N4/SiO2)N/cavity layer/(Si/Si3N4/SiO2)N. The organic chemical compounds are assumed to be separately infiltrated into the cavity layer. The defect layer (DLR) thickness, incident angle, number of unit cells, and the contrast between the high‐ and low‐index layers are varied and the sensitivity and quality factor are found for each case. The sensitivity can be considerably improved by increasing the DLR thickness, angle of incidence, and the contrast between the high‐ and low‐index materials. An extremely high sensitivity (2270.48, 2283.0555, and 2283.75) and quality factor (21.82 × 105, 21.48 × 105 and 21.46 × 105) are obtained for isopropanol, ethanol, and acetone. The results described earlier may pave the way for a practical and useful method of diagnosing chemical compounds.
A novel chemical photonic crystal sensor is proposed for the detection of isopropanol, ethanol, and acetone. The organic chemical compounds are assumed to be separately infiltrated into the cavity layer. An extremely high sensitivity of 2270.48, 2283.0555, and 2283.75 is obtained for isopropanol, ethanol, and acetone.
Chimeric antigen receptor T‐cell therapy toxicities Greenbaum, Uri; Kebriaei, Partow; Srour, Samer A. ...
BJCP. British journal of clinical pharmacology/British journal of clinical pharmacology,
June 2021, Letnik:
87, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Cancer immunotherapy has greatly advanced in recent years, with chimeric antigen receptor (CAR) T cells emerging as an innovative technology that harnesses the immune system to fight malignant ...diseases. These genetically engineered T‐cells have shown encouraging results for B‐cell lymphoid malignancies and are now being explored for other cancer types. However, this novel adoptive cell therapy is associated with a new spectrum of immune‐mediated adverse events and toxicities. As CAR T cells recognize and engage tumour cells, cytokines are secreted and activate other immune cells, frequently leading to rapid development of cytokine release syndrome, which can result in acute deterioration of the patient's clinical condition. In many patients, cytokine release syndrome is mild and easy to manage, but others experience persistent fevers accompanied by hypotension and hypoxia, which require management with immune‐modulatory agents. Another deleterious effect of cytokines released by effector cells is immune effector cell–associated neurotoxicity syndrome. This syndrome, caused by a disruption of the blood–brain barrier as a consequence of the immune process, can result in rapid deterioration in cognitive function. This is often associated with subtle changes in handwriting, often progressing to loss of memory and concentration and reduced ability to name objects or follow commands. In some cases, the neurological state is further compromised by seizures and in rare instances with fulminant life‐threatening cerebral oedema. In this review, we discuss these toxicities, as well as other CAR T‐cell–related immune phenomenon, and address their clinical manifestations, grading, and management options.
Chimeric antigen receptor (CAR) T-cell therapy is the new standard treatment for various indications in patients with advanced hematologic malignancies. Despite the several preclinical and early ...phase clinical trials, the overall clinical experience has been disappointing when applying this innovative therapy in solid tumors. The failure of CAR T-cell therapy and its limited antitumor activity in solid tumors have been attributed to several mechanisms, including tumor antigen heterogeneity, the hostile tumor microenvironment and poor trafficking of CAR T cells into tumor sites, and the unacceptable toxicities in some settings, among others. However, remarkable improvements have been made in understanding many of these failure mechanisms for which several emerging novel approaches are being applied to overcome these challenges. In this review, after a brief historic background for immunotherapy in solid tumors, we highlight the recent developments achieved in CAR T-cell designs, summarize completed clinical trials, and discuss current challenges facing CAR T-cell therapy and the suggested strategies to overcome these barriers.
Summary
Ibrutinib has shown significant activity in patients with relapsed or refractory mantle cell lymphoma (RR‐MCL). We report the long‐term outcome and safety profile of a single‐centre, single ...arm, open‐label, phase 2 study of RR‐MCL treated with IR. Overall, the median follow‐up time was 47 months (range 1–52 months), median duration on treatment was 16 months (range 1–53 months) and median number of treatment cycles was 17 (range 1–56). Twenty‐nine patients (58%) achieved complete remission and of these, 12 patients continue on study. Thirty‐eight patients discontinued treatment, 14 due to disease progression (2 transformed). Patients with blastoid morphology, high risk MCL International Prognostic Index score and high Ki67% had inferior survival. The commonest grade 1–2 toxicities were fatigue, diarrhoea, nausea, arthralgias and myalgias. None had long term toxicities. Median progression‐free survival was 43 months. Eighteen patients (36%) died (14 deaths were MCL‐related). The median overall survival has not been reached. Treatment with IR can provide durable remissions in a subset of patients with RR‐MCL, especially those with low Ki67%. The possible benefit of adding other therapies in combination with IR in RR‐MCL is under exploration.
Opinion statement
For years, upfront autologous hematopoietic cell transplant (auto-HCT) has been the standard of care for younger and physically fit mantle cell lymphoma (MCL) patients after ...chemoimmunotherapy (CIT) induction. Bruton’s tyrosine kinase (BTK) inhibitors have proven to be excellent salvage therapies, but their durability remains a question, especially in high-risk (HR) MCL. Allogeneic HCT (allo-HCT) was the only option for long-term remission and possibly cure for MCL relapse after auto-HCT and sometime as upfront consolidation for a young patient with HR MCL (debatable). We have seen a paradigm shift since the FDA approval in July 2020 of the brexucabtagene autoleucel chimeric antigen receptor T (CAR-T) cell therapy for relapsed and refractory (R/R) MCL with an preliminary evidence suggesting CAR-T may overcome known biological risk factors in MCL. Given its safety profile and excellent efficacy, the role of CAR-T among other approved therapies and HCT may need to be better defined. Based on the current evidence, auto-HCT remains a standard frontline consolidation therapy. CAR-T therapy is a preferred option for patients with relapsed/refractory (R/R) MCL, particularly those who failed BTK inhibitors. In certain high-risk MCL patients (such as high ki 67, TP53 alterations, complex karyotype, blastoid morphology, early relapse after initial diagnosis), CAR-T cell therapy may be considered before BTK inhibitors (preferably on a clinical trial). The role of allo-HCT is unclear in the CAR-T era, but remains a viable option for eligible patients who have no access or who have failed CAR-T therapy. Our review discusses current standards and the shifting paradigms in the indications for HCT and the role of CAR-T cell therapy for MCL. Prospective studies tailored based on risk factors are needed to better define the optimal sequences of HCT and cellular therapy and other approved novel therapies.
The use of plastics can be dangerous due to the numerous industrial chemicals they contain. Di(2‐ethylhexyl) phthalate (DEHP), bisphenol A (BPA), and bisphenol S (BPS) are three detrimental organic ...chemicals that are used in the plastic industry. In this work, a highly sensitive photonic crystal (PCL) sensor is theoretically proposed and numerically simulated as a detector for DEHP, BPA, and BPS organic chemicals. The proposed PCL is a 1D that has the structure (GaAs/Si
3
N
4
/TiN)
N
/cavity layer/(GaAs/Si
3
N
4
/TiN)
N
, where
N
is the number of unit cells (UCs). The DEHP, BPA, and BPS analytes are assumed to be separately infiltrated into the cavity layer between two equal numbers of the UCs. The transmission spectra of the PCL are studied using the transfer matrix (TrMx) technique. The most important performance parameter is sensitivity so we have focused on it. A considerable sensitivity enhancement is obtained by raising the defect layer thickness and incidence angle. High sensitivities of 2350.51, 2168.45, and 2042.08 nm RIU
−1
are obtained for DEHP, BPA, and BPS, respectively. In the results obtained, the way can be paved for a simple technique to detect chemical compounds.
Summary
This cross‐sectional study aimed to develop and validate a patient‐reported outcomes (PROs) assessment tool to assess symptom burden and daily functioning in patients after chimeric antigen ...receptor (CAR) T‐cell therapy, the MD Anderson Symptom Inventory (MDASI‐CAR). The items were generated based on literature review, content elicitation interviews with patients, and clinician's review. The patients completed the MDASI core and module, single‐item quality‐of‐life (QoL) measure and Patient‐Reported Outcomes Measurement Information System‐29 (PROMIS‐29). The psychometric validation analysis was based on the acceptability after item reduction process. The final 10 MDASI‐CAR module items included tremors, fever/chills, headache, balance, dizziness, attention, difficulty speaking, coughing, sexual dysfunction, and diarrhoea with high internal consistency (Cronbach's alpha: MDASI Core, 0.865; MDASI Interference, 0.915; CAR‐T module, 0.746). The MDASI‐CAR has excellent known‐group validity that was demonstrated by differentiate patients based on patient's performance status (Cohen's d for MDASI core = −1.008, interference = −0.771, module = −0.835). Criterion validity was demonstrated by the significant correlations between the MDASI‐CAR composite score, the single QoL item and the relevant domains on PROMIS‐29 (all p < 0.05). This study established the MDASI‐CAR module as a reliable and valid PRO tool for monitoring symptom burden after CAR T‐cell therapy in patients with haematological malignancies. The findings need to be validated with a longitudinal design.
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