Treatment Of non-Hodgkin Lymphoma Patients Research Articles

Adverse drug reactions and nursing interventions in the treatment of non-Hodgkin's lymphoma by Aidi injection.

To explore adverse drug reactions (ADRs) and the effects of nursing interventions after Aidi injection for the treatment of non-Hodgkin's lymphoma (NHL). A total of 104 NHL patients treated in our hospital from March 2019 to March 2020 were selected. All patients underwent conventional chemotherapy, with a concomitant Aidi injection administered at different doses (40, 60, 80, and 100 mL). ADRs were analyzed for all patients, and the clinical outcomes of ADRs were recorded after specific nursing interventions were performed. A total of 17 NHL patients had ADRs, with a total incidence rate of 15.89% (total of 30 ADRs). In terms of different types of ADRs, inappetence accounted for the largest proportion, followed by skin pruritus and fever, phlebitis, nausea and vomiting, and chest distress and/or palpitation, the last of which shared the same proportion as chills and/or low fever and urticaria. The incidence rate of ADRs (total of 18 ADRs, 60.00%) was higher in NHL patients who were given 100 mL of Aidi injection. In terms of age and gender distribution of ADRs, there were 10 males (55.56%) and 7 females (44.44%), and ADRs were more common in patients aged 46-60 years old (total of 6 ADRs, 35.29%). Aidi injection mainly induced mild ADRs (total of 22 ADRs, 73.33%), and the resulting ADRs mostly occurred for <2 hours (total of 19 ADRs, 60.00%). After the specific nursing interventions were performed, no deaths due to ADRs occurred, and 12 (64.71%) cases were cured, 5 (29.41%) cases improved, and 1 (5.88%) case had no progression. Particular attention should be paid to ADRs in the treatment of NHL patients with Aidi injection. After ADRs occur, specific nursing interventions can aid in recovery and lead to improvements in prognosis.

Systems Biology Analyses to Delineate Mechanisms of Anti-CD20 Antibody Resistance in Non-Hodgkin Lymphoma (NHL): Influence of BCR Signaling and the Critical Importance of Calcium Polarization

Introduction:CD20 a cell surface protein selectively expressed in mature B cells is involved in regulation of B cell differentiation and is a well-established target for anti-CD20 therapy in the treatment of B cell malignancies. However, therapeutic resistance to anti-CD20 antibodies, including rituximab and obinutuzumab, continues to remain a major obstacle in the treatment for NHL patients. Known mechanisms of anti-CD20 resistance include loss of CD20 expression, apoptotic dysfunction and/or poor immunoreactivity. Further mechanisms, including potential biologic etiologies, which engender resistance to anti-CD20 antibodies remain largely unclear. We sought to delineate the immuno-biological landscape and mechanisms associated with anti-CD20 resistance via systems biology analyses and immune functional studies with rituximab and obinutuzumab resistant (RR & OR) NHL models in a novel single-cell microfluidics platform.Methods:RR or OR cells (SUDHL4 and SUDHL10) were developed by repeated culturing with chronic low dose exposure to antibody (Ab) drugs. Anti-CD20 resistance was biologically characterized by CD20 immunostaining-flow cytometry, gene expression profiling and systems biology analysis (with Ingenuity Pathway Analysis (IPA) and Gene Set Enrichment Analysis (GSEA). Immunological characterization was performed using NK mediated ADCC activity (AcellaTox-Glo), real-time analysis of NK cell-NHL interaction kinetics by microfluidics and cytokine/immune factor secretion using proximity extension assay (Olink immuno-oncology panel). Ionomycin induced release of Calcium assay was performed using Fluo-4 cell-based assay and plate reader.Results: Flow cytometric studies and ADCC assays using anti-CD20 Abs and primary NK cells, exhibited prominent downregulation of CD20 cell surface expression and markedly decreased NK mediated ADCC activity in RR (11%, P=0.0002) and OR (17%, P=0.001) compared with 10mg/ml of rituximab (51%) or obinutuzumab (56%), respectively, in the parental SUDHL4 cells. The basal NK mediated Furthermore, microfluidic analyses revealed decreased cell-cell interactions among NK cells and anti-CD20 resistant NHL cells in the presence of either antibody. Systems biology analysis of the transcriptome with these RR and OR cells showed downregulation of immune signaling mechanisms closely related MAPK, NFkB, mTOR and JAK/STAT pathways, with partial upregulation of PLCγ, B-cell receptor (BCR) signaling (via western blot). Using the Olink 92-plex cytokine assay, we observed hyposecretion of the majority of cytokines including IL-2, IL-6, IL-8, IL-10, TNFα, IFNγ and FASL all CD20 resistant cells (Fig. 1A). Based in part on these biological changes, we hypothesized that loss of CD20 associated with decreased calcium signaling could be the master regulator observed with anti-CD20 resistance. Assessment of ionomycin-induced releasable calcium showed lack of ionomycin releasable calcium in anti-CD20 resistant cells (Fig. 1B). Treatment with the depolarizing agent, veratridine, restored ionomycin releasable calcium levels, reversed BCR signaling, and it was accompanied with significantly decreased cell viability (60%, P<0.0001) in anti-CD20 resistant cells compared with 100% in sensitive cells. In contrast, use of the hyperpolarizing ivermectin resulted in mimicking anti-CD20 resistant upregulation of BTK and anti-CD20 sensitive cells intolerant to decreased calcium levels.Conclusions: RR and OR NHL cells were associated with downregulation of immune signaling pathways, cytokine hyposecretion, and upregulation of BCR signaling. Furthermore, these observed biological changes were associated with decreased intracellular calcium suggesting its role as a master regulator in anti-CD20 resistance. Utilizing depolarizing and hyperpolarizing pharmacologic agents, we were able to restore favorable signaling changes associated with anti-CD20 antibody sensitivity as well as mimic a resistant phenotype in sensitive cells. Additional investigation of the modulation of calcium signaling as a novel mechanism and target for the treatment of anti-CD20 resistant NHL is warranted. [Display omitted] DisclosuresEvens:Pharmacyclics International DMC: Membership on an entity's Board of Directors or advisory committees; Affimed: Consultancy; Bayer: Consultancy; Janssen: Consultancy; Seattle Genetics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Tesaro: Research Funding; Novartis: Consultancy.

Role of PET / CT in Monitoring Response in Treatment of Non-Hodgkin Lymphoma Patients

Aim of the work: positron emission tomography (PET) response assessment of residual nodal masses in patients with lymphoma after completion of therapy is performed visually using Douveille as the reference. The primary objective of this study was to define the role of PET in response assessment of Non Hodgkin Lymphoma patients and define various response criteria. Patients and methods: our prospective study included 40 patients with Non Hodgkin’s lymphoma diffuse large B cell type assessed for response assessment after completion of therapy, two readers independently assessed response by IHP and Deauville criteria. The addition of morphological parameters on CT was assessed in relation to therapy response. Results: Non Hodgkin lymphoma is one of chemosensitive tumors with high ability of nodal and extranodal spread and PET /CT is more sensitive than CT in monitoring response to treatment in non Hodgkin lymphoma diffuse large B cell type patients. Conclusions: PET/CT is the best tool for evaluation of the response to treatment in patients with Non Hodgkin lymphoma diffuse large B cell type, as well as Douveille criteria represent the accurate indicator of response categories determination.PET/CT has an obvious impact on clinical practice according to the response results and activity of residual lesion.

Radioimmunotherapy: a specific treatment protocol for cancer by cytotoxic radioisotopes conjugated to antibodies.

Radioimmunotherapy (RIT) represents a selective internal radiation therapy, that is, the use of radionuclides conjugated to tumor-directed monoclonal antibodies (including those fragments) or peptides. In a clinical field, two successful examples of this treatment protocol are currently extended by 90Y-ibritumomab tiuxetan (Zevalin) and 131I-tositumomab (Bexxar), both of which are anti-CD20 monoclonal antibodies coupled to cytotoxic radioisotopes and are approved for the treatment of non-Hodgkin lymphoma patients. In addition, some beneficial observations are obtained in preclinical studies targeting solid tumors. To date, in order to reduce the unnecessary exposure and to enhance the therapeutic efficacy, various biological, chemical, and treatment procedural improvements have been investigated in RIT. This review outlines the fundamentals of RIT and current knowledge of the preclinical/clinical trials for cancer treatment.

BEAM chemotherapy and autologous haemopoietic progenitor cell transplantation as front-line therapy for high-risk patients with diffuse large cell lymphoma.

In two consecutive and unselected cohorts of diffuse large cell lymphoma (DLCL) patients with advanced stage disease (IIB or bulk or more) and aged < 60 years, we compared a standard (MACOP-B for 12 weeks, 60 patients) versus a high-dose chemotherapy programme (8 weeks of MACOP-B plus one or two cycles of intensification with mitoxanthrone, dexamethasone, high-dose Ara-C, and finally BEAM chemotherapy with autologous haemopoietic progenitor cell transplantation, 61 patients). 41 patients (68%) in the standard group and 51 (84%) in the high-dose chemotherapy group, achieved a complete remission (CR) or an uncertain complete remission (CRu) (P = 0.0491). With a median follow-up time of 28 months for the high-dose group and 63.5 months for the standard group, the actuarial estimate of event-free survival (EFS) at 2 years demonstrates a significant benefit (70% v 50%, P = 0.03) for patients treated with the intensive regimen. The analysis of subgroups of patients showed that only high-risk patients (two or three risk factors) benefitted from the high-dose chemotherapy programme. Nevertheless, the overall survival does not show a significant difference between the two treatment modalities. The treatment-related morbidity was similar and the mortality rate was 8% in the standard (MACOP-B) group and 3% in the high-dose chemotherapy programme. In conclusion, our results show that high-dose chemotherapy and autologous stem cell transplantation is a safe procedure which should be considered for the front-line treatment of non-Hodgkin lymphoma patients with poor prognostic features.