HLA-DR expression on monocytes and outcome of anti-CD19 CAR T-cell therapy for large B-cell lymphoma.

Despite their unprecedented success in relapsed/refractory (R/R) large B-cell lymphoma (LBCL), anti-CD19 CAR T cells are associated with significant toxicity, and more than half of patients relapse. As monocytes emerged as key players in CAR therapy, we sought to evaluate the evolution of HLA-DR expression on monocytes (mHLA-DR) before and after commercial anti-CD19 CAR T-cell infusion in a large cohort (n = 103) of patients with R/R LBCL and its association with adverse events and treatment response. Cy-Flu-based lymphodepletion (LD) upregulated mHLA-DR in 79% of the cases, whereas in 2l% of cases (15 patients), the mHLA-DR level decreased after LD, and this decrease was associated with poorer outcome. Low mHLA-DR at day minus 7 (D-7) (<13 500 antibodies per cell) before CAR T-cell infusion correlated with older age, poorer performance status, higher tumor burden, and elevated inflammatory markers. With a median follow-up of 7.4 months, patients with low mHLA-DR D-7 exhibited a poorer duration of response and survival than the higher mHLA-DR D-7 group. For toxicity management, tocilizumab was more frequently used in the low-mHLA-DR D-7 group. These data suggest that monocyte dysregulation before LD, characterized by the downregulation of mHLA-DR, correlates with an inflammatory and immunosuppressive tumor environment and is associated with failure of anti-CD19 CAR T cells in patients with R/R LBCL. Modulation of these myeloid cells represents a promising field for improving CAR therapy.

Evaluation of a new ELISA assay for monoclonal free-light chain detection in patients with cardiac amyloidosis.

The causal protein of amyloid light-chain (AL) amyloidosis is a monoclonal immunoglobulin free light chain (mFLC), which must be quantified in the serum for patient diagnosis and monitoring. Several manufacturers commercialize immunoassays that quantify total kappa (κ) and lambda (λ) FLC, but results can differ greatly between these tests. Here, we compared a recently developed enzyme-linked immunosorbent assay (ELISA) (Sebia) with N-Latex immunonephelometry (Siemens) in 96 patients diagnosed with AL amyloidosis (histologically confirmed) and 48 non-AL patients sent to our referral center for suspicion of cardiac amyloidosis. ELISA free-light chain difference (dFLC) were lower than N-Latex values, and agreement between methods was reduced in the case of involved λ FLC. Diagnosis sensitivity and specificity were >85% with both assays. A receiver operating characteristic analysis indicated that ELISA performances could be improved by using a higher value for the lower limit of the κ/λ ratio. We also assessed Freelite (The Binding Site) in a subgroup of these same AL patients, including 18 cases with normal κ/λ ratio by at least one assay. Only two patients had normal κ/λ ratio with all three assays. Overall, ELISA demonstrated slightly lower sensitivity than N-Latex but may be an alternative to nephelometry/turbidimetry in certain difficult cases.

Impact of a Visual Support Dedicated to Prognosis on Symptoms of Stress of ICU Family Members: A Before-and-After Implementation Study.

Family members commonly have inaccurate expectations of patient's prognosis in ICU. Adding to classic oral information, a visual support, depicting day by day the evolution of the condition of the patient, improves the concordance in prognosis estimate between physicians and family members. The objective of this study was to evaluate the impact of this tool on symptoms of anxiety/depression of family members. DESIGN: Bicenter prospective before-and-after study. SETTING: A nonacademic and a university hospital. SUBJECTS: Relatives of consecutive patients admitted in the two ICUs. INTERVENTIONS: In the period "before," family members received classic oral information, and in the period "after," they could consult the visual support in the patient's room. The primary endpoint was the Hospital Anxiety and Depression Scale score of relatives at day 5. Secondary outcomes were the prevalence of symptoms of anxiety (Hospital Anxiety and Depression Scale anxiety subscale score > 7) and depression (Hospital Anxiety and Depression Scale depression subscale score > 7) at day 5 and Hospital Anxiety and Depression Scale score at day 90. MEASUREMENTS AND MAIN RESULTS: A total of 140 patients and their referent family members were included (77 in period before and 63 after). Characteristics of patients of the two groups were similar regarding age, reason for admission, Simplified Acute Physiology Score II at admission, and Sequential Organ Failure Assessment score at day 5. At day 5, median Hospital Anxiety and Depression Scale score was 17 (9-25) before and 15 (10-22) after the implementation of the visual support (p = 0.43). The prevalence of symptoms of anxiety and depression was similar in the two groups (66.2% and 49.4% before and 68.3% and 36.5% after [not significant], respectively). At day 90, median Hospital Anxiety and Depression Scale score was 11 before (7-16) and 9 (5-16) after the implementation of the tool (p = 0.38). CONCLUSIONS: In this study, the use of a visual support tool dedicated to prognosis did not modify the level of stress of family members.

Characteristics of T- and NK-cell Lymphomas After Renal Transplantation: A French National Multicentric Cohort Study.

BACKGROUND: Posttransplant lymphoproliferative disorders (PTLDs) encompass a spectrum of heterogeneous entities. Because the vast majority of cases PTLD arise from B cells, available data on PTLD of T or NK phenotype (T/NK-cell PTLD) are scarce, which limits the quality of the management of these patients. METHODS: All adult cases of PTLD diagnosed in France were prospectively recorded in the national registry between 1998 and 2007. Crosschecking the registry data with 2 other independent national databases identified 58 cases of T/NK-cell PTLD. This cohort was then compared with (i) the 395 cases of B-cell PTLD from the registry, and of (ii) a cohort of 148 T/NK-cell lymphomas diagnosed in nontransplanted patients. RESULTS: T/NK-cell PTLD occurred significantly later after transplantation and had a worse overall survival than B-cell PTLD. Two subtypes of T/NK-cell PTLD were distinguished: (i) cutaneous (28%) and (ii) systemic (72%), the latter being associated with a worse prognosis. Compared with T/NK-cell lymphomas of nontransplanted patients, overall survival of systemic T/NK-cell PTLD was worse (hazard ratio: 2.64 [1.76-3.94]; P < 0.00001). CONCLUSIONS: This difference, which persisted after adjustment on tumoral mass, histological subtype, and extension of the disease at diagnosis could be explained by the fact that transplanted patients were less intensively treated and responded less to chemotherapy.