PAIN MANAGEMENT OF COVID–19 INFECTED PATIENTS AFTER THE VACCINATION: A PROSPECTIVE STUDY

Background: COVID-19 is a severe infectious disease (SID) claimed that >180,000 lives are infected millions in the elderly population globally. Emerging evidences we observed that virus to cause hemorrhagic and immunologic responses impact in all the organs, including lungs, kidneys, eye , the brain, and extremities as well as. We had Material and Methods: performed with prospectively of >1,500 articles and included 525 references from our online databases, including with the Scopus, PubMed, Medline, Google Scholar, and the wave of Sciences. COVID-19 patients are also going through the acute respiratory distress syndrome (ARDS), cytokine storm (CS), acute hypercoagulable state (AHCS), and the autonomic dysfunction (ADF) managed by the multidisciplinary team approach. This is including with Physical medicine rehabilitation, medicine, nursing, nutrition, and rehabilitation and the other important radiological ?ndings. A total no of 30 vaccines under the developmental process (DP), Results: and now newly developed with their guidelines for the better treatment strategies and newly developed protocols are being well implemented. The majority of 80-95% of elderly population those are suffering from neurological diseases (ND-90-95%), Alzheimer's disease (AD-85%, Parkinsonism Diseases (PD-95%) and dementia (D-80%) related illnesses noticed that they are at higher risk during COVID-19 pandemic. The future management for COVID-19 should include B-cell and T-cell immunotherapy in combination with all the emerging prophylaxis is also more helpful. The pain CONCLUSION: management in the neurological disorders (ND) including with all the mental health with several illness aspects of the COVID-19 is the most important side effects of during the pandemic. Hence the national level and International level plan for prevention, diagnosis and treatment for SARS-CoV-2 also affects patients', families', society's neurological disorders (ND), Alzheimer's disease (AD), Parkinsonism Diseases (PD), Dementia Diseases (DD), and the other mental health patients at larger in population. Now growing evidence of re-infection in some neurological disorders (ND) patients is to provide a comprehensive knowledge of SARS-CoV-2-induced with neurological diseases (NDs) and their mechanism of infection (MOI), diagnostics, therapeutics, and their new treatment strategies, focusing with less attended aspects including with the nutritional support, psychological, and physical medicine and rehabilitation and its management are essential for elders, youth, and children.

Clinical characteristics of 17 critically ill children with severe adverse reactions after chimeric antigen receptor T cells therapy / 中国小儿急救医学

Objective:To investigate the clinical characteristics, treatment process and prognosis of children with severe side effects after chimeric antigen receptor T cell immunotherapy(CAR-T), so as to provide evidence for timely intervention after CAR-T treatment.Methods:From June 1, 2015 to May 31, 2020, children with cytokine release syndrome(CRS)or immune cell related neurotoxicity syndrome(ICANS)who were treated with CAR-T therapy in our hospital and revealed severe effects transferred to PICU were included in the study, and their clinical course and multiple laboratory examination data were systematically analyzed.Results:Seventeen children showed CRS reaction and entered PICU after CAR-T therapy.The most common clinical symptoms were respiratory distress(13 cases) and circulatory disorder(10 cases), of which 7 cases were complicated with severe ICANS.Serum interferon -γ(IFN-γ)and interleukin-6(IL-6)levels significantly increased after CAR-T cell infusion, reaching the peak at (5.1±1.6)days.The serum levels of IFN-γ and IL-6 in children with severe CRS were significantly higher than those in children with mild CRS(all P<0.05). The level of serum IL-6 in children with high tumor load was significantly higher than that in children with low tumor load( P<0.05). The mortality rate of children with elevated level of serum TNF-α was higher(5/5 vs.3/11, P<0.05). Children with severe CRS were more likely to develop grade 4 ICANS(4/4 vs.0/3, P<0.05). The mortality rate of children with oxygenation index(P/F value)<200 mmHg(1 mmHg=0.133 kPa) was higher(5/5 vs.2/12, P<0.05). The vasoactive inotropic score[ M( Min, Max)] in the death group was significantly higher than that in survival group[29.5(14.0, 50.0) vs.1.5(0, 25.0), Z=8.000, P=0.027]. Conclusion:Serum IL-6 and IFN-γ are crucial causes of CRS.High tumor load is one of the factors causing high level of serum inflammatory factors.Respiration and circulation systems are the most frequently involved systems.Therefore, the evaluation indexes of these two systems can help us judge the prognosis of children.

A general view of CD33⁺ leukemic stem cells and CAR-T cells as interesting targets in acute myeloblatsic leukemia therapy

Acute myeloblastic leukemia (AML) is the most frequent acute leukemia in adulthood with very poor overall survival rates. In the past few decades, significant progresses had led to the findings of new therapeutic approaches and the better understanding of the molecular complexity of this hematologic malignancy. Leukemic stem cells (LSCs) play a key role in the initiation, progression, regression, and drug resistance of different types of leukemia. The cellular and molecular characteristics of LSCs and their mechanism in the development of leukemia had not yet been specified. Therefore, determining their cellular and molecular characteristics and creating new approaches for targeted therapy of LSCs is crucial for the future of leukemia research. For this reason, the recognition of surface maker targets on the cell surface of LSCs has attracted much attention. CD33 has been detected on blasts in most AML patients, making them an interesting target for AML therapy. Genetic engineering of T cells with chimeric antigen receptor (CAR-T cell therapy) is a novel therapeutic strategy. It extends the range of antigens available for use in adoptive T-cell immunotherapy. This review will focus on CAR-T cell approaches as well as monoclonal antibody (mAB)-based therapy, the two antibody-based therapies utilized in AML treatment.

Allogeneic CAR-T for treatment of relapsed and/or refractory multiple myeloma: four cases report and literatures review / 中华血液学杂志

Objective@#To investigate the safety and efficacy of allogeneic CAR-T cells in the treatment of relapsed/refractory multiple myeloma (RRMM) .@*Methods@#CAR-T cells were prepared from peripheral blood lymphocytes of HLA mismatch healthy donors. Median age was 55 (48-60) . Allogeneic cells were derived from 3 HLA haploidentical donors and 1 HLA completely mismatch unrelated donor. Four patients with RRMM were conditioned with FC regimen followed by CAR-T cell transfusion. They were infused into CART-19 (1×107/kg on day 0) and (4.0-6.8) ×107/kg CART-BCMA cells as split-dose infusions (40% on day 1 and 60% on day 2) . The adverse reactions and clinical efficacy were observed during follow-up after infusion, and the amplification and duration of CAR-T cells in vivo were monitored by PCR technique.@*Results@#CAR-T cells were successfully infused in 3 of the 4 RRMM patients according to the study plan, and the infusion in one patient was delayed by 1 day due to high fever and elevated creatinine levels on day 3. The side effects included hematological and non-hematological toxicity, grade 3 hematological toxicity in 2 patients, grade 3 CRS in 1 one, grade 1 CRES in 1 one, prolonged APTT in 3 ones, tumor lysis syndrome in 1 one, mixed chimerism detected STR and clinical GVHD manifestation in 1 one. According to the efficacy criterias of IMWG, 2 patients acquired PR, 1 MR, and 1 SD respectively. Progression-free survival was 4 (3-5) weeks and overall survival was 63 (3-81) weeks. CAR T cells were amplified 2.2 (2-14) times in the patients with a median survival time of 10 (8-36) days.@*Conclusions@#Small sample studies suggested that GVHD may be present in the treatment of RRMM with allogeneic CAR-T cells. There were early clinical transient events after transfusion. Low amplification and short duration of CAR-T cells in vivo may be the main factors affecting the efficacy.

Immunotherapy of Gastrointestinal Stromal Tumors / 中国医学科学院学报

Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract and respond poorly to conventional radiochemotherapy.Complete excision is the only possible way to cure GISTs.Although targeted therapy is effective for GISTs,multiple and/or secondary mutations of KIT or PDGFRA gene have lead to increased drug resistance and disease relapse.A variety of tumor infiltrating immune cells and complex immune microenvironments have been found in GISTs.Many immune cells participate in the occurrence and development of GISTs and play key roles in targeted therapy.The feasibility and effectiveness of immunotherapy for GISTs have been well demonstrated in preclinical and clinical studies.

Allogeneic CAR-T for treatment of relapsed and/or refractory multiple myeloma: four cases report and literatures review / 中华血液学杂志

Objective: To investigate the safety and efficacy of allogeneic CAR-T cells in the treatment of relapsed/refractory multiple myeloma (RRMM) . Methods: CAR-T cells were prepared from peripheral blood lymphocytes of HLA mismatch healthy donors. Median age was 55 (48-60) . Allogeneic cells were derived from 3 HLA haploidentical donors and 1 HLA completely mismatch unrelated donor. Four patients with RRMM were conditioned with FC regimen followed by CAR-T cell transfusion. They were infused into CART-19 (1×10(7)/kg on day 0) and (4.0-6.8) ×10(7)/kg CART-BCMA cells as split-dose infusions (40% on day 1 and 60% on day 2) . The adverse reactions and clinical efficacy were observed during follow-up after infusion, and the amplification and duration of CAR-T cells in vivo were monitored by PCR technique. Results: CAR-T cells were successfully infused in 3 of the 4 RRMM patients according to the study plan, and the infusion in one patient was delayed by 1 day due to high fever and elevated creatinine levels on day 3. The side effects included hematological and non-hematological toxicity, grade 3 hematological toxicity in 2 patients, grade 3 CRS in 1 one, grade 1 CRES in 1 one, prolonged APTT in 3 ones, tumor lysis syndrome in 1 one, mixed chimerism detected STR and clinical GVHD manifestation in 1 one. According to the efficacy criterias of IMWG, 2 patients acquired PR, 1 MR, and 1 SD respectively. Progression-free survival was 4 (3-5) weeks and overall survival was 63 (3-81) weeks. CAR T cells were amplified 2.2 (2-14) times in the patients with a median survival time of 10 (8-36) days. Conclusions: Small sample studies suggested that GVHD may be present in the treatment of RRMM with allogeneic CAR-T cells. There were early clinical transient events after transfusion. Low amplification and short duration of CAR-T cells in vivo may be the main factors affecting the efficacy.

Treatment of central nervous system leukemia with CD19-chimeric antigen receptor T-cell immunotherapy: two cases report and literature review / 中华血液学杂志

Objective@#To explore the efficacy and safety of chimeric antigen receptor T (CAR-T) cells in the treatment of central nervous system leukemia (CNSL).@*Methods@#Two leukemia patients with CNSL were treated with CD19-CAR-T cells. The process and results of the entire treatment is reported and related literature review is conducted.@*Results@#The patients were diagnosed as acute myeloid leukemia (AML)-M2 with B lymphoid antigen expression and B cell acute lymphoblastic leukemia(B-ALL) by morphology and immunophenotype assay. The immunophenotype was consistent with the abnormal manifestations of AML-M2 and B-ALL. Their clinical manifestations and laboratory tests met the diagnostic criteria of CNSL. The diagnosis was clear and the two patients were treated with CD19-CAR-T cell immunotherapy. Central nervous system symptoms were relieved. The imaging abnormalities of patient one has disappeared but cytokines release syndrome (CRS) occurred during the treatment. Cerebrospinal fluid of patient two was negative and no obvious CRS reaction was found.@*Conclusions@#CAR-T cell immunotherapy is likely to induce the remission of CNSL and improve the prognosis.

Progress in the treatment of aggressive B-cell non-Hodgkin lymphoma / 白血病·淋巴瘤

The 23rd Congress of the European Hematology Association (EHA) was held in Stockholm, Sweden from June 14-17, 2018. The latest analysis of three chimeric antigen receptor T-cell treatments for diffuse large B-cell lymphoma and clinical data from a number of immunotargeting drugs were presented at this congress, all showing encouraging results. The recent progress of aggressive B-cell non-Hodgkin lymphoma is briefly introduced in this paper.

Treatment of central nervous system leukemia with CD19-chimeric antigen receptor T-cell immunotherapy: two cases report and literature review / 中华血液学杂志

Objective: To explore the efficacy and safety of chimeric antigen receptor T (CAR-T) cells in the treatment of central nervous system leukemia (CNSL). Methods: Two leukemia patients with CNSL were treated with CD19-CAR-T cells. The process and results of the entire treatment is reported and related literature review is conducted. Results: The patients were diagnosed as acute myeloid leukemia (AML)-M(2) with B lymphoid antigen expression and B cell acute lymphoblastic leukemia(B-ALL) by morphology and immunophenotype assay. The immunophenotype was consistent with the abnormal manifestations of AML-M(2) and B-ALL. Their clinical manifestations and laboratory tests met the diagnostic criteria of CNSL. The diagnosis was clear and the two patients were treated with CD19-CAR-T cell immunotherapy. Central nervous system symptoms were relieved. The imaging abnormalities of patient one has disappeared but cytokines release syndrome (CRS) occurred during the treatment. Cerebrospinal fluid of patient two was negative and no obvious CRS reaction was found. Conclusions: CAR-T cell immunotherapy is likely to induce the remission of CNSL and improve the prognosis.

Therapeutic value of immune cell therapy based on T memory stem cells and central memory T cells for hematological malignancies / 白血病·淋巴瘤

In recent years,cellular immune therapy represented by antigen-chimeric receptor T cells (CAR-T) has made a great breakthrough in the treatment of hematological malignancies.T memory stem cells (TSCM) and central memory T cells (TCM) can be used as most powerful carrier for T cell immunotherapy,however,how to regulate their differentiation in vitro and in vivo as well as how to construct a strong treatment system while without potential side effect become quite interesting.This article summarized the studies from the 58th America Society of Hematology Annual Meeting regarding to values and associated research progress about TsCM and TCM in hematological malignancies.

Chimeric antigen receptor T-cell immunotherapy and its applications in hematological malignancies immunotherapy / 上海交通大学学报（医学版）

Chimeric antigen receptor T-cell (CAR-T) immunotherapy is a new type of immunotherapy,which has been developed rapidly in recent years.By using gene recombination and transfection techniques,CAR-modified effector T cells that specially recognize tumor-associated antigen was produced,which show better properties of targeting,killing activity and durability than conventional T cells.With the development of translational medicine research,CAR-T technology has experienced four generations of optimization and innovation,and presented a promising clinical efficacy in the treatment of various cancers,especially hematological malignancies.However,there are also potential risks with clinical use of this new technology,such as the off-target effect and cytokine storm.In this review,the progress,side effects,coping strategy,and development prospects of CAR-T in hematological malignancies immunotherapy were discussed.