Plasma cell reservoir, evaluated by CXCR5-T follicular helper cell compartment and BCMA, in CART19 treated pediatric patients, for immunoglobulin replacement treatment optimization.

Project summary

Preliminary data suggest that, in the context of anti-CD19 chimeric antigen receptor (CART19) therapy, the variability of plasma cell reservoir might determine the degree of hypogammaglobulinemia, and secondary antibody deficiency observed in treated patients and the need for immunoglobulin replacement therapy (IgRT).

With this purpose, we have selected two promising peripheral blood biomarkers with the objective of quantifying plasma cell reservoir in CART19-treated pediatric patients for acute lymphoblastic leukemia (ALL): peripheral T follicular helper cells (Tfh) and solubilized form of B-cell maturation antigen (sBCMA). These biomarkers would avoid the need of performing biopsies to directly quantify plasma cells in bone marrow or mucosal sites.

We will measure Tfh, sBCMA and serum immunoglobulin levels at baseline and every 3 months during B-cell aplasia and after CART19 loss, and correlate their dynamics, in a pediatric population of ALL CART19 treated patients. Moreover, we will correlate Tfh and sBCMA levels with prior treatments received for ALL, age, CART19 construct and interleukin-6 levels during CART19 infusion, in order to identify the factors affecting plasma cell reservoir.

Biographical Sketch

Laia Alsina completed her medicine degree in 2000 at the University of Barcelona (Spain). She board-certified in pediatrics in 2005 at the Hospital Sant Joan de Déu of Barcelona (Spain) and completed her PhD in Immune reconstitution, HIV and HAART at the University of Barcelona in 2008. From 2008 to 2010 she acquired experience in the field of transcriptomics in primary immunodeficiencies (PID) of innate immunity during her postdoctoral fellowship at the Baylor Institute for Immunology Research (Dallas, USA) and had medical training at the Jeffrey Modell Foundation Center for PID at the Children's Medical Hospital in Dallas (USA).

Since 2011 she is the research group leader of the "Study group of pediatric immunological disorders" at the Institut de Recerca Sant Joan de Déu in Barcelona. She is currently Chief of the Pediatric Allergy and Clinical Immunology Department at Hospital Sant Joan de Déu (Barcelona, Spain) since 2020.

She has two main focuses: 

• identifying novel targeted therapeutic approaches for patients with PID and immune dysregulation manifestations and 
• reorganizing the diagnostic and therapeutic journey of patients with moderate-severe forms of PID and/or immune dysregulation manifestations.