Profilaxis antiemética en pacientes con neoplasias hematológicas que reciben protocolos de acondicionamiento para el trasplante de células madre hematopoyéticas: protocolo de estudio para una revisión sistemática / Antiemetic prophylaxis in hematologic malignancies patients receiving conditioning protocols for hematopoietic stem cell transplantation: A study protocol for a systematic review

Objetivo las náuseas y los vómitos inducidos por la quimioterapia siguen siendo un reto importante para los pacientes que recibieron un trasplante de células madre hematopoyéticas. Este estudio tiene como objetivo sintetizar la evidencia disponible sobre los regímenes de profilaxis antiemética en los pacientes con neoplasias hematológicas que recibieron un trasplante de células madre hematopoyéticas, con el fin de identificar el mejor estándar de cuidado. Métodos se llevará a cabo una revisión sistemática utilizando las bases de datos MEDLINE a través de PubMed, EMBASE, Clinical-Trials.gov y Cochrane. Se considerarán los estudios escritos en inglés, francés, italiano o español. Después de seleccionar los estudios de acuerdo con los criterios de inclusión y exclusión, 2 revisores independientes extraerán los datos y evaluarán el riesgo de sesgo en los artículos seleccionados. Este protocolo se ha elaborado de acuerdo con las recomendaciones de las guías PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols). Este protocolo está registrado en PROSPERO (Prospective Register of Ongoing Systematic Reviews) CRD42023406380. Discusión las náuseas y los vómitos inducidos por la quimioterapia son un efecto secundario incapacitante que supone un reto importante para los pacientes con neoplasias hematológicas. A pesar de la publicación de diversas guías sobre profilaxis antiemética, ninguna de ellas incluye recomendaciones específicas para cada régimen de quimioterapia. Por lo tanto, analizar los regímenes de profilaxis antiemética primaria en los pacientes con neoplasias hematológicas que recibieron un trasplante de progenitores hematopoyéticos sería valioso para mejorar la calidad de vida de estos pacientes. (AU)

Objective Chemotherapy-induced nausea and vomiting continue to pose a significant challenge for patients undergoing hematopoietic stem cell transplantation. This study aims to synthesize available evidence on antiemetic prophylaxis regimens in patients with hematologic malignancies undergoing hematopoietic stem cell transplantation, in order to identify the best standard of care. Methods A systematic review will be conducted using MEDLINE via PubMed, EMBASE, ClinicalTrials.gov., and Cochrane databases. Studies written in English, French, Italian or Spanish will be considered. After screening the literature according to the inclusion and exclusion criteria, two independent reviewers will extract data and assess the risk of bias in eligible articles. This protocol has been prepared according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. This protocol is registered in the Prospective Register of Ongoing Systematic Reviews (PROSPERO) CRD42023406380. Discussion Chemotherapy-induced nausea and vomiting is a debilitating side effect that presents a significant challenge for patients with hematologic malignancies. Despite the publication of various guidelines, none of them includes specific recommendations for each chemotherapy regimen. Therefore, analyzing the primary antiemetic prophylaxis regimens in patients with hematologic malignancies undergoing hematopoietic stem cell transplantation would be valuable in enhancing patients' quality of life. (AU)

Antiemetic prophylaxis in hematologic malignancies patients receiving conditioning protocols for hematopoietic stem cell transplantation: A study protocol for a systematic review. / [Artículo traducido] Profilaxis antiemética en pacientes con neoplasias hematológicas que reciben protocolos de acondicionamiento para el trasplante de células madre hematopoyéticas: protocolo de estudio para una revisión sistemática.

OBJECTIVE: Chemotherapy-induced nausea and vomiting continue to pose a significant challenge for patients undergoing hematopoietic stem cell transplantation. This study aims to synthesize available evidence on antiemetic prophylaxis regimens in patients with hematologic malignancies undergoing hematopoietic stem cell transplantation, in order to identify the best standard of care. METHODS: A systematic review will be conducted using MEDLINE via PubMed, EMBASE, ClinicalTrials.gov., and Cochrane databases. Studies written in English, French, Italian or Spanish will be considered. After screening the literature according to the inclusion and exclusion criteria, two independent reviewers will extract data and assess the risk of bias in eligible articles. This protocol has been prepared according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. This protocol is registered in the Prospective Register of Ongoing Systematic Reviews (PROSPERO) CRD42023406380. DISCUSSION: Chemotherapy-induced nausea and vomiting is a debilitating side effect that presents a significant challenge for patients with hematologic malignancies. Despite the publication of various guidelines, none of them includes specific recommendations for each chemotherapy regimen. Therefore, analyzing the primary antiemetic prophylaxis regimens in patients with hematologic malignancies undergoing hematopoietic stem cell transplantation would be valuable in enhancing patients' quality of life.

Antiemetic prophylaxis in hematologic malignancies patients receiving conditioning protocols for hematopoietic stem cell transplantation: A study protocol for a systematic review.

OBJECTIVE: Chemotherapy-induced nausea and vomiting continue to pose a significant challenge for patients undergoing hematopoietic stem cell transplantation. This study aims to synthesize available evidence on antiemetic prophylaxis regimens in patients with hematologic malignancies undergoing hematopoietic stem cell transplantation, in order to identify the best standard of care. METHODS: A systematic review will be conducted using MEDLINE via PubMed, EMBASE, Clinical-Trials.gov., and Cochrane databases. Studies written in English, French, Italian, or Spanish will be considered. After screening the literature according to the inclusion and exclusion criteria, 2 independent reviewers will extract data and assess the risk of bias in eligible articles. This protocol has been prepared according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. This protocol is registered in the Prospective Register of Ongoing Systematic Reviews (PROSPERO) CRD42023406380. DISCUSSION: Chemotherapy-induced nausea and vomiting is a debilitating side effect that presents a significant challenge for patients with hematologic malignancies. Despite the publication of various guidelines, none of them include specific recommendations for each chemotherapy regimen. Therefore, analyzing the primary antiemetic prophylaxis regimens in patients with hematologic malignancies undergoing hematopoietic stem cell transplantation would be valuable in enhancing patients' quality of life.

The shape of cancer relapse: Topological data analysis predicts recurrence in paediatric acute lymphoblastic leukaemia.

Although children and adolescents with acute lymphoblastic leukaemia (ALL) have high survival rates, approximately 15-20% of patients relapse. Risk of relapse is routinely estimated at diagnosis by biological factors, including flow cytometry data. This high-dimensional data is typically manually assessed by projecting it onto a subset of biomarkers. Cell density and "empty spaces" in 2D projections of the data, i.e. regions devoid of cells, are then used for qualitative assessment. Here, we use topological data analysis (TDA), which quantifies shapes, including empty spaces, in data, to analyse pre-treatment ALL datasets with known patient outcomes. We combine these fully unsupervised analyses with Machine Learning (ML) to identify significant shape characteristics and demonstrate that they accurately predict risk of relapse, particularly for patients previously classified as 'low risk'. We independently confirm the predictive power of CD10, CD20, CD38, and CD45 as biomarkers for ALL diagnosis. Based on our analyses, we propose three increasingly detailed prognostic pipelines for analysing flow cytometry data from ALL patients depending on technical and technological availability: 1. Visual inspection of specific biological features in biparametric projections of the data; 2. Computation of quantitative topological descriptors of such projections; 3. A combined analysis, using TDA and ML, in the four-parameter space defined by CD10, CD20, CD38 and CD45. Our analyses readily extend to other haematological malignancies.

Monitoring of kinetics and exhaustion markers of circulating CAR-T cells as early predictive factors in patients with B-cell malignancies.

Purpose: CAR-T cell therapy has proven to be a disruptive treatment in the hematology field, however, less than 50% of patients maintain long-term response and early predictors of outcome are still inconsistently defined. Here, we aimed to optimize the detection of CD19 CAR-T cells in blood and to identify phenotypic features as early biomarkers associated with toxicity and outcomes. Experimental design: In this study, monitoring by flow cytometry and digital PCR (dPCR), and immunophenotypic characterization of circulating CAR-T cells from 48 patients treated with Tisa-cel or Axi-cel was performed. Results: Validation of the flow cytometry reagent for the detection of CAR-T cells in blood revealed CD19 protein conjugated with streptavidin as the optimal detection method. Kinetics of CAR-T cell expansion in blood confirmed median day of peak expansion at seven days post-infusion by both flow cytometry and digital PCR. Circulating CAR-T cells showed an activated, proliferative, and exhausted phenotype at the time of peak expansion. Patients with increased expansion showed more severe CRS and ICANs. Immunophenotypic characterization of CAR-T cells at the peak expansion identified the increased expression of co-inhibitory molecules PD1 and LAG3 and reduced levels of the cytotoxicity marker CD107a as predictors of a better long-term disease control. Conclusions: These data show the importance of CAR-T cells in vivo monitoring and identify the expression of PD1LAG3 and CD107a as early biomarkers of long-term disease control after CAR-T cell therapy.

A Mathematical Description of the Bone Marrow Dynamics during CAR T-Cell Therapy in B-Cell Childhood Acute Lymphoblastic Leukemia.

Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated high rates of response in recurrent B-cell Acute Lymphoblastic Leukemia in children and young adults. Despite this success, a fraction of patients' experience relapse after treatment. Relapse is often preceded by recovery of healthy B cells, which suggests loss or dysfunction of CAR T-cells in bone marrow. This site is harder to access, and thus is not monitored as frequently as peripheral blood. Understanding the interplay between B cells, leukemic cells, and CAR T-cells in bone marrow is paramount in ascertaining the causes of lack of response. In this paper, we put forward a mathematical model representing the interaction between constantly renewing B cells, CAR T-cells, and leukemic cells in the bone marrow. Our model accounts for the maturation dynamics of B cells and incorporates effector and memory CAR T-cells. The model provides a plausible description of the dynamics of the various cellular compartments in bone marrow after CAR T infusion. After exploration of the parameter space, we found that the dynamics of CAR T product and disease were independent of the dose injected, initial B-cell load, and leukemia burden. We also show theoretically the importance of CAR T product attributes in determining therapy outcome, and have studied a variety of possible response scenarios, including second dosage schemes. We conclude by setting out ideas for the refinement of the model.

High-Dimensional Analysis of Single-Cell Flow Cytometry Data Predicts Relapse in Childhood Acute Lymphoblastic Leukaemia.

Artificial intelligence methods may help in unveiling information that is hidden in high-dimensional oncological data. Flow cytometry studies of haematological malignancies provide quantitative data with the potential to be used for the construction of response biomarkers. Many computational methods from the bioinformatics toolbox can be applied to these data, but they have not been exploited in their full potential in leukaemias, specifically for the case of childhood B-cell Acute Lymphoblastic Leukaemia. In this paper, we analysed flow cytometry data that were obtained at diagnosis from 56 paediatric B-cell Acute Lymphoblastic Leukaemia patients from two local institutions. Our aim was to assess the prognostic potential of immunophenotypical marker expression intensity. We constructed classifiers that are based on the Fisher's Ratio to quantify differences between patients with relapsing and non-relapsing disease. We also correlated this with genetic information. The main result that arises from the data was the association between subexpression of marker CD38 and the probability of relapse.