Immune reconstitution and evolution of B-cell-stimulating cytokines after R-CHOP therapy for HIV-associated DLBCL.

Autor:	Liévin R; Department of Hematology and Oncology, Hospital of Versailles, Le Chesnay, France.; Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, Imagine Institute, University of Paris, INSERM U1163, Paris, France., Maillard A; Médecine Intensive et Réanimation, Hôpital Saint-Louis, AP-HP, Université Paris Cité, Paris, France., Hendel-Chavez H; Department of Immunology, Assistance Publique Hôpitaux de Paris, Hôpital Bicêtre, Kremlin-Bicêtre, France.; INSERM U1186, Institut Gustave Roussy, Villejuif, France., Krzysiek R; Department of Immunology, Assistance Publique Hôpitaux de Paris, Hôpital Bicêtre, Kremlin-Bicêtre, France.; INSERM UMR 996, Inflammation Microbiome and Immunosurveillance, Paris-Saclay University, Orsay, France., Lancar R; INSERM UMR 996, Inflammation Microbiome and Immunosurveillance, Paris-Saclay University, Orsay, France., Algarte-Genin M; Institut Pierre Louis d'Epidémiologie et de Santé Publique, IPLESP, Sorbonne Université, INSERM UMR-S 1136, Paris, France., Costagliola D; Institut Pierre Louis d'Epidémiologie et de Santé Publique, IPLESP, Sorbonne Université, INSERM UMR-S 1136, Paris, France., Assoumou L; Institut Pierre Louis d'Epidémiologie et de Santé Publique, IPLESP, Sorbonne Université, INSERM UMR-S 1136, Paris, France., Taoufik Y; Department of Immunology, Assistance Publique Hôpitaux de Paris, Hôpital Bicêtre, Kremlin-Bicêtre, France.; INSERM U1186, Institut Gustave Roussy, Villejuif, France., Besson C; Department of Hematology and Oncology, Hospital of Versailles, Le Chesnay, France.; Université Versailles Saint Quentin en Yvelines, Université Paris-Saclay, Montigny le Bretonneux, France.; INSERM U1018, Centre for Research in Epidemiology and Population Health, Villejuif, France.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2024 Dec 10; Vol. 8 (23), pp. 6017-6027.
DOI:	10.1182/bloodadvances.2024014116
Abstrakt:	Abstract: HIV infection is associated with an increased risk of diffuse large B-cell lymphoma (DLBCL). In this prospective study, we analyzed the evolution of B-cell activating cytokines (interleukin-6 [IL-6], IL-10, and B-cell activating factor [BAFF]) and main functional subsets of circulating B and T cells in 51 patients with HIV-associated DLBCL treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, Oncovin [vincristine], and prednisone). R-CHOP therapy was associated with a decrease of IL-10, whereas IL-6 levels fluctuated, and BAFF levels increased during the first 3 months and decreased thereafter. We observed a rapid rise in CD19+ B cells composed mostly of naïve B cells whereas marginal zone-like B cells and memory B cells recovered gradually. With a median follow-up of 41 months, progression-free survival and overall survival at 5 years were 61.8% (95% confidence interval [CI], 47.6-80.4) and 67.4% (95% CI, 53.4-85.0), respectively. Progression (17.5%) and sepsis (12.5%) were the main causes of death. Baseline risk factors for death and progression were poor revised International Prognostic Index (P = .049), natural killer cell lymphopenia (P = .001), lower proportion of naïve B cells (P = .017), and higher IL-6 serum levels (P = .001). Our data suggest that patients treated with R-CHOP for HIV-associated DLBCL have a disturbed peripheral B-cell compartment and that the low pool size of circulating naïve B cells negatively affects their clinical outcome. In an era of development of B-cell-depleting therapies including B-cell-targeting chimeric antigen receptor T cells, assessment of perturbations within nontumoral B-cell counterparts are warranted for risk profiling in HIV-associated DLBCL. This trial was registered at www.ClinicalTrials.gov as #NCT01164436. (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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