Consensus guidelines and recommendations for the management and response assessment of chimeric antigen receptor T-cell therapy in clinical practice for relapsed and refractory multiple myeloma: a report from the International Myeloma Working Group Immunotherapy Committee.

Chimeric antigen receptor (CAR) T-cell therapy has shown promise in patients with late-line refractory multiple myeloma, with response rates ranging from 73 to 98%. To date, three products have been approved: Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), which are approved by the US Food and Drug Administration, the European Medicines Agency, Health Canada (ide-cel only), and Brazil ANVISA (cilta-cel only); and equecabtagene autoleucel (eque-cel), which was approved by the Chinese National Medical Products Administration. CAR T-cell therapy is different from previous anti-myeloma therapeutics with unique toxic effects that require distinct mitigation strategies. Thus, a panel of experts from the International Myeloma Working Group was assembled to provide guidance for clinical use of CAR T-cell therapy in myeloma. This consensus opinion is from experts in the field of haematopoietic cell transplantation, cell therapy, and multiple myeloma therapeutics.

Expert review on soft-tissue plasmacytomas in multiple myeloma: definition, disease assessment and treatment considerations.

In this review, two types of soft-tissue involvement in multiple myeloma are defined: (i) extramedullary (EMD) with haematogenous spread involving only soft tissues and (ii) paraskeletal (PS) with tumour masses arising from skeletal lesions. The incidence of EMD and PS plasmacytomas at diagnosis ranges from 1·7% to 4·5% and 7% to 34·4% respectively. EMD disease is often associated with high-risk cytogenetics, resistance to therapy and worse prognosis than in PS involvement. In patients with PS involvement a proteasome inhibitor-based regimen may be the best option followed by autologous stem cell transplantation (ASCT) in transplant eligible patients. In patients with EMD disease who are not eligible for ASCT, a proteasome inhibitor-based regimen such as lenalidomide-bortezomib-dexamethasone (RVD) may be the best option, while for those eligible for high-dose therapy a myeloma/lymphoma-like regimen such as bortezomib, thalidomide and dexamethasone (VTD)-RVD/cisplatin, doxorubicin, cyclophosphamide and etoposide (PACE) followed by SCT should be considered. In both EMD and PS disease at relapse many strategies have been tried, but this remains a high-unmet need population.

Diagnostic accuracy of immunological methods in patients with tuberculous pleural effusion from Venezuela.

In recent years, better diagnostics for tuberculosis (TB) has received increasing attention, especially the diagnosis of tuberculous pleural effusion, which is difficult and at present the main tool in TPE diagnostic is pleural effusion smear and culture, but unfortunately, sensitivities are low, therefore better TPE diagnostic tools are needed. The aim of this study was to find a diagnostic algorithm to assess the progress in TPE diagnostic at the Hospital Vargas de Caracas, that permits identification of the majority of patients, at a satisfactory cost-benefit ratio, evaluating the levels of IFN-gamma and IL-12p40 in pleural effusion and serum, as well as the antibody reactivity in order to compare it with microbiological tests. A total of 60 individuals with pleural effusion were studied; 20 patients with tuberculous pleural effusion (TPE) formed the patient group and 40 patients with non-tuberculous pleural effusion (NTPE) formed the control group. The levels of IFN-gamma and IL-12p40 in effusion and serum and class and subclasses of IgG reactivity to Mycobacterium tuberculosis antigens were measured by ELISA. The utility of these methods for diagnosis of TPE was evaluated using receiver operating characteristic (ROC) curve analysis. The results of the 11 immunological methods evaluated showed that the anti-PPD IgG2 method was able to reach the highest specificity of 95% (CI: 88.3-101.8), positive predictive value (PPV) = 75 (at 30% sensitivity); while that the overall sensitivity of methods was between 95% and 30%, of these, two methods reached higher sensitivities; increased levels of pleural IFN-gamma, with a sensitivity of 95% (CI: 85.5-104.5) with the highest negative predictive value (NPV) = 97, (at 82.5% specificity), followed by decreased levels of serum IL-12p40 with a sensitivity of 95% (CI: 85.5-104.5), NPV = 95.2 (at 50% specificity). In contrast, microbiological methods showed that smear had a sensitivity of only 20%, while smear plus culture had, a sensitivity of 70%. Considering that TPE represents approximately 15 percent of all the TB clinically diagnosed at the Hospital Vargas de Caracas, in those patients with preliminary microbiology negativity in the effusion, the combined analysis of pleural IFN-gamma and anti-PPD IgG2 could represent a fast and effective diagnostic algorithm for improving the diagnosis previous to obtain culture results. In this way treatment against TB could be initiated or the need to cytological and pleural biopsy could be considered.

Diagnostic accuracy of immunological methods in patients with tuberculous pleural effusion from Venezuela / Precisión diagnóstica de métodos inmunológicos en pacientes con tuberculosis pleural de Venezuela

In recent years, better diagnostics for tuberculosis (TB) has received increasing attention, especially the diagnosis of tuberculous pleural effusion, which is difficult and at present the main tool in TPE diagnostic is pleural effusion smear and culture, but unfortunately, sensitivities are low, therefore better TPE diagnostic tools are needed. The aim of this study was to find a diagnostic algorithm to assess the progress in TPE diagnostic at the Hospital Vargas de Caracas, that permits identification of the majority of patients, at a satisfactory cost-benefit ratio, evaluating the levels of IFN-g and IL-12p40 in pleural effusion and serum, as well as the antibody reactivity in order to compare it with microbiological tests. A total of 60 individuals with pleural effusion were studied; 20 patients with tuberculous pleural effusion (TPE) formed the patient group and 40 patients with non-tuberculous pleural effusion (NTPE) formed the control group. The levels of IFN-g and IL-12p40 in effusion and serum and class and subclasses of IgG reactivity to Mycobacterium tuberculosis antigens were measured by ELISA. The utility of these methods for diagnosis of TPE was evaluated using receiver operating characteristic (ROC) curve analysis. The results of the 11 immunological methods evaluated showed that the anti-PPD IgG2 method was able to reach the highest specificity of 95% (CI: 88.3-101.8), positive predictive value (PPV)=75 (at 30% sensitivity); while that the overall sensitivity of methods was between 95% and 30%, of these, two methods reached higher sensitivities; increased levels of pleural IFN-g, with a sensitivity of 95% (CI: 85.5-104.5) with the highest negative predictive value (NPV)=97, (at 82.5% specificity), followed by decreased levels of serum IL-12p40 with a sensitivity of 95% (CI: 85.5-104.5), NPV=95.2 (at 50% specificity). In contrast, microbiological methods showed that smear had a sensitivity of only 20%, while smear plus ...

Recientemente existe un gran interés hacia un mejor y más rápido diagnóstico de tuberculosis (TB), especialmente de tuberculosis pleural, el cual es difícil. Al presente las principales herramientas diagnósticas son la baciloscopia y el cultivo de líquido pleural; desafortunadamente, las sensibilidades de estos métodos son bajas, por lo que el desarrollo de nuevas herramientas diagnósticas es necesario. El objetivo del presente estudio consistió en encontrar un algoritmo que permita la rápida identificación de la mayoría de los pacientes con TB pleural que ingresan en el Hospital Vargas de Caracas a un buen costo-beneficio. Para esto se evaluaron los niveles de las citocinas Interferón-gamma (IFN-g) y la Interleucina 12p40 (IL-12p40) en líquido pleural y suero, así como la reactividad de anticuerpos contra antígenos de Mycobacterium tuberculosis. Se estudiaron 60 individuos con derrame pleural; 20 individuos con líquido pleural tuberculoso (LPT) conformaron el grupo de pacientes y 40 individuos con líquido pleural no tuberculoso (LPNT) el grupo de controles. La técnica de inmunoensayo de ELISA fue utilizada para medir los niveles de IFN-g y IL-12p40; así como las reactividades de los diversos isotipos y subclases de inmunoglobulina G (IgG) frente a antígenos del bacilo. La utilidad de los métodos fue evaluada utilizando el análisis de las curvas ROC (receiver operating characteristic). Los resultados de los 11 métodos inmunológicos evaluados mostraron que el método IgG2 anti-PPD alcanzó la mayor especificidad de 95%, (CI: 88,3-101,8) con un valor predictivo positivo (VPP) de 75. La sensibilidad de los métodos estuvo entre 30% y 95%; dos métodos alcanzaron altas sensibilidades: los altos niveles de IFN-g en líquido pleural, con sensibilidad de 95% (CI: 85,5-104,5), con un valor predictivo negativo (VPN) de 97, seguido de los bajos niveles de IL-12p40 en suero, con una sensibilidad de 95% (CI: 85,5-104,5) con un VPN de 95,2. En contraste, ...

Multiple myeloma in serologic complete remission after autologous stem cell transplantation: impact of bone marrow plasma cell assessment by conventional morphology on disease progression.

The current definition of complete remission (CR) in multiple myeloma (MM) requires a negative serum and urine immunofixation (IFE) and <5% bone marrow plasma cells (BMPCs). The aim of this study was to determine the value of BMPCs count by standard microscopic evaluation in patients with MM in serologic CR after autologous stem cell transplantation (ASCT). Thirty-five patients with a median follow-up after ASCT of 7.3 years were studied. The percentage of BMPCs was an independent predictor of progression in multivariate model (hazard ratio 2.02, P = .009). Patients with >1.5% BMPCs (median: 0.8%) after ASCT had an increased risk of progression (P = .016) and a trend toward a shorter survival (P = .195). In conclusion, conventional morphology of bone marrow is a useful and rapid tool as a first step to assess the residual tumor mass in patients with MM in CR after ASCT, and it constitutes a strong predictor for disease progression.

Relación entre IhA secretora, atopía y estres en niños asmáticos de la Isla de Coche / Relationship between the IgA secretory atopia and stress in asthmatis children of the island of Coche

La IgA es fundamental en la homéostasis de las mucosas y mediante el proceso de esclusión inmune evita el paso de macromoléculas alergénicas desde el tracto gastrointestinal; se modifica por factores diversos, como estress y el sistema neuroendocrino; y guarda relación con el asma bronquial, junto a factores inmunes, ambientales y psicológicos. Se evaluó 72 niños en edad preescolar y escolar de el Cardón, Isla de Coche, parasitados por helmintos y alta incidencia de asma; y 20 niños de Carapita, Caracas no asmáticos. Se determinaron niveles de IgA secretora en saliva, IgE total en suero y CD23s por el método de ElISA; expresión de receptores de membrana CD20 y CD23 por citometría de flujo; y niveles de stress emocional por la prueba de Madeleine Thomas. Se buscó relacionar IgAs con la presencia de atopia, asma, infecciones helmínticas intestinales y factores psicológicos como la ansiedad. Se encontraron mayores de IgAs en los niños atápicos (Isla de Coche) que en los atópicos (Carapita), y una evaluación global de las IgAs junto con IgE en el primer grupo. No se encontró diferencia significativa entre el grupo de parasitados y no parasitados en cuanto a IgAs aunque sí mayor nivel de IgE en los parasitados. Se evidenció mayores concentraciones de CD23s en los asmáticos. Los niveles de IgAs fueron menores en los niños inversamente sus valores con el número de crisis en el grupo de asmáticos y también con sus niveles de ansiedad