Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: a phase 2 trial.

Axicabtagene ciloleucel (axi-cel) demonstrated superior efficacy compared to standard of care as second-line therapy in patients with high-risk relapsed/refractory (R/R) large B cell lymphoma (LBCL) considered eligible for autologous stem cell transplantation (ASCT); however, in clinical practice, roughly half of patients with R/R LBCL are deemed unsuitable candidates for ASCT. The efficacy of axi-cel remains to be ascertained in transplant-ineligible patients. ALYCANTE, an open-label, phase 2 study, evaluated axi-cel as a second-line therapy in 62 patients with R/R LBCL who were considered ineligible for ASCT.

FDG-PET/CT in Lymphoma: Where Do We Go Now?

18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) is an essential part of the management of patients with lymphoma at staging and response evaluation. Efforts to standardize PET acquisition and reporting, including the 5-point Deauville scale, have enabled PET to become a surrogate for treatment success or failure in common lymphoma subtypes. This review summarizes the key clinical-trial evidence that supports PET-directed personalized approaches in lymphoma but also points out the potential place of innovative PET/CT metrics or new radiopharmaceuticals in the future.

Post-treatment positron emission tomography-computed tomography is highly predictive of outcome in Plasmablastic lymphoma.

Purpose: Plasmablastic lymphoma (PBL) is a rare variant of diffuse large B cell lymphomas (DLBCL) clinically characterized by a poorer prognostic. Few clinical and imaging data are available and derived from pooled case reports and small series. The aim of the study was to evaluate the FDG avidity at baseline and the utility of 18-Fluorodeoxyglucose (FDG) positron-emission-tomography/computed-tomography (PET/CT) for staging and response assessment.

Magnetic Resonance Imaging of Parotid Gland Tumors: Dynamic Contrast-Enhanced Sequence Evaluation.

Objective: The aim of the study was to evaluate dynamic contrast-enhanced magnetic resonance (MR) imaging in the characterization of parotid gland tumors.

Methods: Fifty-five parotid lesions in 55 patients were retrospectively included. Two observers interpreted 2 reading protocols derived from all MR imaging in 2 distinct sessions, independently and blinded.

Association between textural and morphological tumor indices on baseline PET-CT and early metabolic response on interim PET-CT in bulky malignant lymphomas.

Purpose: We investigated whether metabolic, textural, and morphological tumoral indices evaluated on baseline PET-CT were predictive of early metabolic response on interim PET-CT in a cohort of patients with bulky Hodgkin and non-Hodgkin malignant lymphomas.

Methods: This retrospective study included 57 patients referred for initial PET-CT examination. In-house dedicated software was used to delineate tumor contours using a fixed 30% threshold of SUV max and then to compute tumoral metabolic parameters (SUV max, mean, peak, standard deviation, skewness and kurtosis, metabolic tumoral volume (MTV), total lesion glycolysis, and area under the curve of the cumulative histogram), textural parameters (Moran's and Geary's indices, energy, entropy, contrast, correlation derived from the gray-level co-occurrence matrix, area under the curve of the power spectral density, auto-correlation distance, and granularity), and shape parameters (surface, asphericity, convexity, surfacic extension, and 2D and 3D fractal dimensions).

Impact of the Adaptive Statistical Iterative Reconstruction Technique on Radiation Dose and Image Quality in Bone SPECT/CT.

Unlabelled: The purpose of this study was to compare a routine bone SPECT/CT protocol using CT reconstructed with filtered backprojection (FBP) with an optimized protocol using low-dose CT images reconstructed with adaptive statistical iterative reconstruction (ASiR).

Methods: In this prospective study, enrolled patients underwent bone SPECT/CT, with 1 SPECT acquisition followed by 2 randomized CT acquisitions: FBP CT (FBP; noise index, 25) and ASiR CT (70% ASiR; noise index, 40). The image quality of both attenuation-corrected SPECT and CT images was visually (5-point Likert scale, 2 interpreters) and quantitatively (contrast ratio [CR] and signal-to-noise ratio [SNR]) estimated.

B-cell polyclonal activation and Epstein-Barr viral abortive lytic cycle are two key features in acute infectious mononucleosis.

Background: Acute infectious mononucleosis (AIM) is generally associated with a large EBV B cell reservoir cells and an intense B-cell polyclonal activation whereas the number of quiescent EBV-infected memory B cells in chronically EBV-infected healthy controls is very low.

Objectives: To evaluate the extent and functionality of ex vivo B-cell polyclonal activation, quantify the EBV DNA integrated in B cells, enumerate the functional EBV DNA reservoir in B cells and circulating B cells spontaneously secreting EBV antigens in AIM.

Study Design: Circulating B cells and B cells differentiating into plamablasts and plasma cells, early (BZLF1)- and late viral antigen (gp350)-secreting-cells (SCs) were enumerated in six AIM patients and seven healthy EBV carriers.

CD4+ T cells spontaneously producing human immunodeficiency virus type I in breast milk from women with or without antiretroviral drugs.

Background: Transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding may involve both cell-free and cell-associated virus. This latter viral reservoir remains, however, to be fully explored. CD4+ T cell-associated virus production in breast milk was therefore investigated.

Human milk-derived B cells: a highly activated switched memory cell population primed to secrete antibodies.

While secretory Abs have been extensively explored in human breast milk, the existence, features, and functions of B lymphocytes remain largely unexplored in this compartment. We analyzed breast milk and blood lymphocytes from 21 lactating women, including 12 HIV-1-infected mothers. Breast milk B cells displayed a phenotype of class-switched memory B cells, with few IgD(+) memory and naive B cells.

Close association of CD8+/CD38 bright with HIV-1 replication and complex relationship with CD4+ T-cell count.

Background: Measuring lymphocyte activation provides information in addition to CD4(+) T-cell count for immune monitoring of HIV-1 infected patients. CD38 is a well-established activation marker that is generally analyzed on the whole population of CD8(+) T-cells. Focusing specifically on CD38 high expression (CD8(+)/CD38(bright)) may be an interesting surrogate gating strategy because CD38(bright) characterizes principally activated memory cells.

Functional Epstein-Barr virus reservoir in plasma cells derived from infected peripheral blood memory B cells.

The Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes latency in resting memory B lymphocytes, and is involved in oncogenesis through poorly understood mechanisms. The EBV lytic cycle is initiated during plasma cell differentiation by mRNAs transcripts encoded by BZLF1, which induce the synthesis of EBV proteins such as the immediate-early antigen ZEBRA and the late membrane antigen gp350. Therefore, we assessed the capacity of circulating EBV-infected B lymphocytes from healthy EBV-seropositive subjects to enter and complete the EBV lytic cycle.

Long-term persistence of memory B cells specific for hepatitis B surface antigen in HIV-1-infected patients.

To investigate the maintenance of long-term memory B cells specific for hepatitis B surface antigen (HBsAg), purified blood B cells were polyclonally stimulated and cells secreting antibodies directed to HBsAg (HBs-SC) enumerated by ELISpot. HBs-SC were found in 18/20 HIV-1-infected patients with either natural or vaccinal immunity to hepatitis B virus, including six subjects with serum anti-hepatitis B surface antibody levels less than 10 mIU/ml. A lower number of HBs-SC was found in HBsAg-vaccinated patients compared with vaccinated controls.

Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients.

Background: The presence of HIV-1 preintegration reservoir was assessed in an in vitro experimental model of latent HIV-1 infection, and in patients treated or not with highly active antiretroviral therapy (HAART).

Results: In resting CD4+ T lymphocytes latently infected in vitro with HIV-1, we demonstrated that the polyclonal activation induced a HIV-1 replication, which could be prevented by the use of an HIV-1 integrase inhibitor. We also showed that this reservoir was labile since the rescuable HIV-1-antigens production from unintegrated HIV-1 genomes declined over time.

Isolation and characterization of HIV-1-infected resting CD4+ T lymphocytes in breast milk.

An HIV-1 reservoir comprised primarily of latently infected resting CD4+ T lymphocytes that can be stimulated in vivo to produce virus may play a critical role in mother-to-child postnatal transmission of HIV-1 by breastfeeding. Here, we describe an experimental protocol for the detection of resting CD4+ T cell HIV-1 reservoir from breast milk. We adapted a method for the purification of resting CD4+ T lymphocytes in blood to isolate resting CD4+ T cells in breast milk from HIV-1-infected-lactating women (n=18) and from controls (n=3).

Detection of memory B lymphocytes specific to hepatitis B virus (HBV) surface antigen (HBsAg) from HBsAg-vaccinated or HBV-immunized subjects by ELISPOT assay.

To improve the investigation of the role of human memory B lymphocytes following hepatitis B virus (HBV) infection or vaccination, we developed a method to characterize circulating memory B cells specific to hepatitis B surface antigen (HBsAg). Our approach combined: (1) purification of CD19+ cells, (2) CD40-CD40L polyclonal stimulation, and (3) enumeration of memory B cells differentiated into anti-HBs antibody (Ab)-secreting cells (HBs-SCs) by a HBs-ELISPOT assay. In this way, HBs-SCs were detected in 17 HBsAg-vaccinated and nine HBV-immunized subjects including four individuals with serum anti-HBs Ab levels < 10 mIU/ml, but not in six controls.

Detection of a large T-cell reservoir able to replicate HIV-1 actively in breast milk.

In breast milk and paired blood samples of nine HIV-1-infected lactating women, we undertook a study to detect a CD4 T-cell reservoir and to investigate its capacity to enter viral production after activation. Breast milk-infected CD4 T cells have a greater capacity to produce viral particles actively than blood CD4 T cells. This observation may explain the apparent paradox of a transmissible viral infection from a body fluid with a low viral concentration.