dc.creator | Molinos-Quintana, Águeda | es |
dc.creator | Alonso-Saladrigues, Anna | es |
dc.creator | Herrero, Blanca | es |
dc.creator | Caballero Velázquez, Teresa | es |
dc.creator | Galán-Gómez, Víctor | es |
dc.creator | Panesso, Melissa | es |
dc.creator | Torrebadell, Montserrat | es |
dc.creator | Delgado-Serrano, Javier | es |
dc.creator | Pérez de Soto, Concepción | es |
dc.creator | Pérez Simón, José Antonio | es |
dc.date.accessioned | 2024-04-11T15:04:30Z | |
dc.date.available | 2024-04-11T15:04:30Z | |
dc.date.issued | 2024-01-16 | |
dc.identifier.citation | Molinos-Quintana, Á., Alonso-Saladrigues, A., Herrero, B., Caballero Velázquez, T., Galán-Gómez, V., Panesso, M.,...,Pérez Simón, J.A. (2024). Impact of disease burden and late loss of B cell aplasia on the risk of relapse after CD19 chimeric antigen receptor T Cell (Tisagenlecleucel) infusion in pediatric and young adult patients with relapse/refractory acute lymphoblastic leukemia: role of B-cell monitoring. Frontiers In Immunology, 14, 1280580. https://doi.org/10.3389/fimmu.2023.1280580. | |
dc.identifier.issn | 1664-3224 | es |
dc.identifier.uri | https://hdl.handle.net/11441/156819 | |
dc.description.abstract | Introduction: Loss of B-cell aplasia (BCA) is a well-known marker of functional
loss of CD19 CAR-T. Most relapses and loss of BCA occur in the first months after
CD19 CAR-T infusion. In addition, high tumor burden (HTB) has shown to have a
strong impact on relapse, especially in CD19-negative. However, little is known
about the impact of late loss of BCA or the relationship between BCA and preinfusion tumor burden in patients infused with tisagenlecleucel for relapsed/
refractory B-cell acute lymphoblastic leukemia. Therefore, the optimal
management of patients with loss of BCA is yet to be defined.
Methods: We conducted a Spanish, multicentre, retrospective study in patients
infused with tisagenlecleucel after marketing authorization. A total of 73
consecutively treated patients were evaluated.
Results: Prior to infusion, 39 patients had HTB (≥ 5% bone marrow blasts)
whereas 34 had a low tumor burden (LTB) (<5% blasts). Complete remission
was achieved in 90.4% of patients, of whom 59% relapsed. HTB was associated
with inferior outcomes, with a 12-month EFS of 19.3% compared to 67.2% in
patients with LTB (p<0.001) with a median follow-up of 13.5 months (95% CI 12.4
– 16.2). In the HTB subgroup relapses were mainly CD19-negative (72%) whereas
in the LTB subgroup they were mainly CD19-positive (71%) (p=0.017). In the LTB
group, all CD19-positive relapses were preceded by loss of BCA whereas only
57% (4/7) of HTB patients experienced CD19-positive relapse. We found a
positive correlation between loss of BCA and CD19-positive relapse (Rsquared: 74) which persisted beyond six months post-infusion. We also
explored B-cell recovery over time using two different definitions of loss of
BCA and found a few discrepancies. Interestingly, transient immature B-cell
recovery followed by BCA was observed in two pediatric patients. In conclusion,
HTB has an unfavorable impact on EFS and allo-SCT might be considered in all
patients with HTB, regardless of BCA. In patients with LTB, loss of BCA preceded
all CD19-positive relapses. CD19-positive relapse was also frequent in patients
who lost BCA beyond six months post-infusion. Therefore, these patients are still
at significant risk for relapse and close MRD monitoring and/or therapeutic
interventions should be considered. | es |
dc.format | application/pdf | es |
dc.format.extent | 14 p. | es |
dc.language.iso | eng | es |
dc.publisher | Frontiers Media S.A. | es |
dc.relation.ispartof | Frontiers In Immunology, 14, 1280580. | |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | B cell aplasia | es |
dc.subject | Late B-cell recovery | es |
dc.subject | Pre-infusion tumor burden | es |
dc.subject | CD19 CART-cells, relapsed/refractory acute lymphoblastic leukemia | es |
dc.subject | Tisagenlecleucel | es |
dc.subject | B-cell monitoring | es |
dc.title | Impact of disease burden and late loss of B cell aplasia on the risk of relapse after CD19 chimeric antigen receptor T Cell (Tisagenlecleucel) infusion in pediatric and young adult patients with relapse/refractory acute lymphoblastic leukemia: role of B-cell monitoring | es |
dc.type | info:eu-repo/semantics/article | es |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Instituto de Biomedicina de Sevilla (IBIS) | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Medicina | es |
dc.relation.publisherversion | https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1280580/full | es |
dc.identifier.doi | 10.3389/fimmu.2023.1280580 | es |
dc.journaltitle | Frontiers In Immunology | es |
dc.publication.volumen | 14 | es |
dc.publication.initialPage | 1280580 | es |