Liévin Raphaël, Maillard Alexis, Hendel-Chavez Houria, Krzysiek Roman, Lancar Remi, Algarte-Genin Michele, Costagliola Dominique, Assoumou Lambert, Taoufik Yassine, Besson Caroline
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.
Blood Adv. 2024 Dec 10;8(23):6017-6027. doi: 10.1182/bloodadvances.2024014116.
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.
HIV感染与弥漫性大B细胞淋巴瘤（DLBCL）风险增加相关。在这项前瞻性研究中，我们分析了51例接受R-CHOP（利妥昔单抗、环磷酰胺、阿霉素、长春新碱和泼尼松）治疗的HIV相关DLBCL患者中B细胞激活细胞因子（白细胞介素-6 [IL-6]、IL-10和B细胞激活因子[BAFF]）的演变以及循环B细胞和T细胞的主要功能亚群。R-CHOP治疗与IL-10水平降低相关，而IL-6水平波动，BAFF水平在最初3个月升高，此后降低。我们观察到CD19+B细胞迅速增加，主要由幼稚B细胞组成，而边缘区样B细胞和记忆B细胞逐渐恢复。中位随访41个月时，5年无进展生存率和总生存率分别为61.8%（95%置信区间[CI]，47.6 - 80.4）和67.4%（95%CI，53.4 - 85.0）。疾病进展（17.5%）和脓毒症（12.5%）是主要死亡原因。死亡和进展的基线风险因素包括修订后的国际预后指数较差（P = 0.049）、自然杀伤细胞淋巴细胞减少（P = 0.001）、幼稚B细胞比例较低（P = 0.017）以及IL-6血清水平较高（P = 0.001）。我们的数据表明，接受R-CHOP治疗的HIV相关DLBCL患者外周B细胞区室紊乱，循环幼稚B细胞库容量低对其临床结局产生负面影响。在包括B细胞靶向嵌合抗原受体T细胞在内的B细胞清除疗法发展的时代，有必要评估非肿瘤性B细胞对应物内的扰动，以对HIV相关DLBCL进行风险评估。该试验已在www.ClinicalTrials.gov注册，编号为#NCT01164436。
