Critically ill patients with acute leukemia often require an intensive care unit (ICU) admission. As major therapeutic advances have been made during the last decades, the aim of this study was to assess temporal trends in ICU mortality, and identify prognostic factors to inform clinician decision-making. We conducted an individual participant data meta-analysis of studies including adults with acute leukemia admitted to the ICU. Patients with a history of allogeneic hematopoietic stem cell transplantation were excluded. Mixed-effects logistic regression models, accounting for center of ICU admission as a random variable, evaluated factors associated with ICU mortality, with particular focus on year of ICU admission, age (> 65 years) and invasive mechanical ventilation. A total of 2003 patients from 55 ICUs across 19 countries were included (median age 58 years [IQR 44–67]; 72
Preoperative anemia (PA) and red blood cell transfusion (RBT) are associated with decreased survival in several cancers. In muscle-invasive bladder cancer (MIBC), anemia is frequent and may be worsened by neoadjuvant chemotherapy (NAC). While PA’s impact is known in patients undergoing cystectomy without NAC, its prognostic value in the current multimodal approach remains unclear. We retrospectively analyzed patients with cT2–T4 N0–N2 M0 MIBC treated with cisplatin-based NAC followed by radical cystectomy and lymphadenectomy between 2011 and 2022. We recorded the lowest hemoglobin value from NAC start to surgery (PA), use of RBT during NAC, and iron or vitamin B9/B12 supplementation. This monocentric cohort included 175 patients (77
ABSTRACT:The prognostic heterogeneity of multiple myeloma is mainly driven by the genomic features of myeloma cells. The International Myeloma Society (IMS)/International Myeloma Working Group (IMWG) recently proposed a high-risk (HR) genomic model to have a consensus definition of genomic risk. We performed next-generation sequencing in the form of a panel on samples from 6528 patients with newly diagnosed multiple myeloma (NDMM) and 1583 patients at first relapse between 2019 and 2024. We observed that 22.4% of patients at diagnosis and 36.7% of patients at first relapse were classified as high risk according to the Consensus Genomic Staging. Clinical data were available for 2695 patients at diagnosis. After a median follow-up of 35 months, the median progression-free survival (PFS) was 30 months for patients with HR NDMM and 51 months for standard-risk (SR) patients (P< .0001). The HR cytogenetic criteria from the Revised- International Staging System score were not able to differentiate between HR and SR patients based on the IMS/IMWG genomic subgroups. Looking at each criterion independently, we found that the presence of del(17p), TP53 mutation, biallelic del(1p32), or the combination of intermediate-risk cytogenetics (gain 1q, del(1p32), t(4;14), t(14;16), t(14;20)) significantly reduced the PFS when compared with SR patients. Moreover, patients with several cumulating criteria had an even worse prognosis. Among SR patients, classified according to the genomic definition with normal creatinine, the median PFS for those with high β2-microglobulin was not significantly different from that of patients with normal β2-microglobulin level. This study validated the IMS/IMWG genomic definition of HR myeloma in a large cohort of patients diagnosed from 2019 onwards.
ABSTRACT:Large B-cell lymphoma (LBCL) patients failing anti-CD19 chimeric antigen receptor (CAR) T-cell therapy exhibit poor prognosis. Most progressions/relapses occur within 3 months from infusion whereas only a few events occur thereafter (late failure, [LF]). We analyze features, treatments, and outcomes of patients with LF from DESCAR-T, a nationwide registry collecting real-life data for patients treated with approved CAR T-cell therapy in France. Between July 2018 and March 2024, 298 (39.9%) LBCL LF patients (median age, 62 years [range, 18-79]; male, 61.7%) were collected from DESCAR-T. Most patients had diffuse LBCL (n = 205 [68.8%]), advanced stage disease (84.6%), and age-adjusted International Prognostic Index of 2 to 3 (59.3%) at CAR T-cell eligibility. After failure, 76.5% of patients received a systemic therapy and overall response rate was 22.6% (complete response, 18%). At a median follow-up since first LF event of 13.8 months (95% confidence interval [CI], 12.1-15.4), the median overall survival and progression-free survival 2 (PFS-2) were 4.4 (95% CI, 3.8-5.8) and 13.2 (95% CI, 9.6-18) months, respectively. Compared with chemotherapy (hazard ratio [HR], 0.350; 95% CI, 0.193-0.633) and with pooled other treatment groups (HR, 0.483; 95% CI, 0.290-0.805), salvage treatment with bispecific antibodies (bsAb) after CAR T-cell failure showed better PFS-2. Radiotherapy obtained prolonged responses in some patients with 12-month PFS-2 of 41.5% (95% CI, 22.5-59.5). This work is, to our knowledge, the first study describing LBCL patients with LF after CAR T-cells. bsAb seem to be more effective compared with other strategies in the LF setting and this should be considered in the design of new clinical trials.
Inflammatory breast cancer (IBC) is a rare but aggressive subtype of breast cancer characterized by rapid progression and poor prognosis. Despite its distinct clinical presentation and molecular features, the immune landscape of IBC and its potential role in driving the aggressive phenotype remain poorly understood. This study aimed to characterize the spatial immune landscape of IBC, compare it with that of subtype-matched non-inflammatory breast cancer (nIBC), and evaluate the prognostic implications of immune cell composition and localization. We analyzed pre-treatment tumor samples from 161 IBC and 115 subtype-matched nIBC patients using immunohistochemistry (IHC) for CD8, FOXP3, CD79α, CD163, and PD-L1. Digital image analysis quantified the immune cell density and relative marker area in the tumor area (TA) and invasive margin (IM). Associations with clinicopathological features, pathological response to neoadjuvant chemotherapy (NACT), and survival were assessed using multivariate logistic regression and Cox proportional hazards models. Transcriptomic validation was performed using Affymetrix gene expression data and consensus TME deconvolution. IBC showed higher infiltration of CD163 + tumor-associated macrophages (TAMs) compared to nIBC. Gene expression data confirmed IHC findings, and pathway analysis linked high TAM density with inflammatory and proliferative pathways. The spatial distribution of immune cells was prognostically relevant, with high CD8 + T-cell infiltration (OR: 0.41, 95
