In September, 2019, a 36-year-old woman with no prior medical history, was admitted to the nephrology department of the Hôpitaux Universitaires Henri Mondor (Créteil, France) with unexplained weight ...loss, hypercalcaemia, and acute kidney injury (AKI). A CT scan showed several enlarged lymph nodes and bilateral nephromegaly (the right kidney was 180 mm in size and the left kidney 168 mm) with right uretero-hydronephrosis. 18F-FDG PET–MRI showed a notable accumulation of 18F-FDG in several lesions, including the enlarged lymph nodes, bone lesions, and peritoneal nodules. Treatment was completed with seven additional cycles of R-CHOP14 and two cycles of high-dose methotrexate. 18F-FDG PET–MRI after 6 months of treatment showed complete resolution of the lesions including renal parenchymal abnormal 18F-FDG uptake (figure, B).
Keywords: AL amyloidosis; cardiac amyloidosis; venetoclax; BH3 mimetics; apoptosis CAPTION(S): Table SI. Haematological, cardiac, and renal response in evaluable patients treated with venetoclax. ...ORR, overall response rate; CR, complete response; VGPR, very good partial response PR, partial response; SD stable disease; PD, progressive disease. Table SII. Adverse events reported during treatment with venetoclax, as recorded according to the Common Terminology Criteria for Adverse Events version v5.0. Fig S1. Overall survival, estimated by Kaplan Meier curve, from the time of venetoclax initiation to death. Byline: Helene Pasquer, Karim Belhadj, Jehan Dupuis, Sylvia Oghina, Antoine Galat, Amandine Ladaique, Alizee Maarek, Louise Roulin, Romain Gounot, Elsa Poulot, Asma Beldi-Ferchiou, Valerie Molinier-Frenkel, Corinne Haioun, Thibaud Damy, Fabien Le Bras, Francois Lemonnier
Posttransplant Lymphoproliferative Disorders (PTLD) 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.
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.
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 (HR: 2.641.76-3.94; p<0.00001).
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.
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.
•Low prelymphodepletion mHLA-DR correlates with older age, poorer ECOG performance status, higher tumor burden, and systemic inflammation.•Low prelymphodepletion mHLA-DR is associated with poorer ...duration of response and survival in LBCL treated with anti-CD19 CAR T cells.
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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.
OBJECTIVES:
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.
Background: Primary cerebral lymphoma (PCNSL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL) with a particularly poor outcome compared to systemic DLBCL. Several prognostic scores have ...been developed for PCNSL. These include the International Extranodal Lymphoma Study Group (IELSG) score with five prognostic factors (patient age, serum lactate dehydrogenase LDH level, Eastern Cooperative Oncology Group performance status PS, deep brain involvement and cerebrospinal fluid CSF protein level), and the Memorial Sloan-Kettering Cancer Center (MSKCC) score, which is based on age and the Karnofsky Performance Score (KPS). However, the reproducibility of these two scoring systems is low, and the IESLG score requires CSF protein and LDH levels evaluation, which are not often available. None of these scores incorporate data on nutritional status, in particular albumin, which has been shown to be an important prognostic factor in systemic DLBCL. In addition, a recent study demonstrated that the muscle density and mass determined by imaging segmentation, were strong prognostic factors for newly diagnosed systemic DLBCL patients (Jullien et al. Cancers 2021). Our aim was to determine whether these imaging data were also predictive factors for outcome in newly diagnosed diffuse large B-cell PCNSL patients. Methods: For each patient included in the study, muscle mass and density were estimated using skeletal muscle index (SMI) and mean skeletal muscle radiation attenuation (SMRA), respectively. SMI and SMRA were computed at L3 level using the whole-body scan (WBS) performed at the diagnosis of PCNSL, by the mean of an automated segmenting algorithm. Muscle characteristics were then classified as normal or low using already validated cut-off according to patients' age and body mass index (Westenberg et al. Sci Rep 2023). Patients' outcomes were then compared based on their muscle quality, albumin level at diagnosis and other clinical variables commonly included in PCNSL prognostic scores. Results: Between 2015 and 2022, 98 consecutive diffuse large B-cell PCNSL patients were newly diagnosed at Hematology Department of Hospital Lyon Sud, France. Among them, 77 had WBS at diagnosis with available data for this study. The median age was 69 years (range 24-87) and 22 patients (29%) presented an altered ECOG PS (PS 3-4 score). All patients were treated with first-line high-dose methotrexate-based chemotherapy in combination with rituximab. SMI was normal in 64 patients (83%) and 17 patients (17%) had low SMI. Patients with low SMI had more frequently an altered PS (p=0.07) and had lower albumin level (mean 36.7 g/L vs 32.0 g/L, p=0.007). SMRA was normal in 30 patients (39%) and 47 patients (61%) had low SMRA. Patients with low SMRA were older (60 vs 70 years old, p=0.001). In univariate analysis, patients with low SMI had worse outcome with significantly shorter overall survival (p=0.002, median OS, 21.4 months vs not reached) and a trend towards shorter event-free survival (p=0.055, median EFS, 11.9 months vs 42.3 months, Figure 1). No significant prognostic difference was seen for SMRA for EFS or OS. The multivariate analysis showed that SMI (Hazard ratio HR=3.33, 95% confidence interval 95%CI= 1.21-9.20, p=0.02) and age (HR =1.86, 95%CI =1.15-3.0, p=0.012) were strongly associated with OS but not tumor localization (HR =1.46, 95%CI =0.60-3.55, p=0.4), PS (HR = 1.54, 95%CI =0.65-3.65, p=0.32) and albumin level (HR =1.05, 95%CI =0.47-2.32, p=0.91). Age was significantly associated with EFS (HR=1.4, p = 0.04) with a more limited association of SMI with EFS (HR=2.03, p=0.095). In exploratory subgroup analyses, we showed that SMI still influenced OS in patients with PS 4 (10 months vs not reached, p= 0.002), suggesting that SMI may be a more appropriate prognostic factor than PS, especially for patients with motor deficit for whom PS is difficult to estimate. Conclusions: This retrospective analysis of newly diagnosed PCNSL patients showed a significant association between decreased muscle mass, measured by SMI and overall survival, after controlling for other prognostic variables. These findings warrant confirmative analyses to explore the relationship between muscle mass/density and diffuse large B-cell PCNSL patient's outcome and integrate SMI in PCNSL prognostic scores.
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