The activity of anti-CD19 CAR T cell therapy in chronic lymphocytic leukemia (CLL) with Richter's transformation (RT) to aggressive large B cell lymphoma (LBCL) is largely unknown. In a multicenter ...retrospective study, we report the safety and efficacy of CAR T cell therapy in patients with RT (n=30) compared to patients with aggressive B cell lymphoma (n=283) and patients with transformed indolent Non-Hodgkins Lymphoma (iNHL) (n=141) between April 2016 and January 2023. Two-thirds of patients received prior therapy for CLL before RT and 89% of them received B-cell receptor and B-cell lymphoma 2 (BCL-2) inhibitors. Toxicities of CAR T cell therapy in RT were similar to other lymphomas, with no fatalities related to cytokine release syndrome or immune effector-cell associated neurotoxicity synderome. The 100-day overall response rate and complete response rates in patients with RT were 57% and 47%, respectively. With a median follow up of 19 months, the median overall survival (OS) was 9.9 months in patients with RT compared to 18 months in de-novo LBCL and not reached in patients with transformed iNHL. The OS at 12 months was 45% in patients with RT compared with 62% and 75% in patients with de novo LBCL and transformed iNHL, respectively. In a multivariate analysis, worse OS was associated with RT histology, elevated LDH, and more prior lines of therapy. CAR T cell therapy can salvage a proportion of patients with CLL and RT exposed to prior targeted agents; however, efficacy in RT is inferior compared to de novo LBCL and transformed iNHL
The myeloproliferative neoplasms (MPN) are clonal diseases that confer an increased risk of thrombohemorrhagic complications. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disease ...associated with an increased thrombotic risk. Small PNH clones are prevalent in aplastic anemia and myelodysplastic syndrome patients, but their prevalence in MPN patients is unknown.
Consecutive patients with MPN followed up at a single center were recruited. PNH clones were analyzed in erythrocytes and white blood cells by flow cytometry.
PNH clones were detected in 2% of patients and were more common in JAK2 V617F positive patients. We could not detect any differences in clinical manifestations or complications in patients either with or without PNH clones because of the small patient numbers.
The prevalence of PNH clones in MPN is similar to that described in myelodysplastic syndromes. Whether PNH clones influence MPN phenotype and complications should be studied prospectively in larger patient cohorts and over long-term follow-up.
Paroxysmal nocturnal hemoglobinuria (PNH) and myeloproliferative neoplasm (MPN) are diseases associated with increased thrombosis. PNH clones are commonly found in other hematologic diseases, such as myelodysplastic syndromes and aplastic anemia. The presence of PNH clones was studied in consecutive MPN patients. A prevalence of 2% and an association with the JAK2 mutation was found. Presence of a PNH clone could potentially influence the clinical course of MPN.
High serum lactate is associated with increased mortality in septic shock patients. Metformin alters lactate metabolism, and may affect its prognostic value. We compared, between metformin users and ...nonusers, the prognosis of extremely elevated plasma lactate levels in patients with septic shock.
The electronic medical records (EMR) of patients admitted to the emergency room between January 2011 and June 2013 were reviewed. The study cohort comprised patients with an initial diagnosis of septic shock and blood lactate higher than 10 mmol/L. The selected population was divided into two groups: metformin users (exposed) and metformin nonusers (unexposed). The primary outcome measured was inhospital mortality.
The study included 44 metformin users and 118 nonusers. Metformin users were similar to nonusers with respect to levels of lactate, HCO3, and blood pH; however, they were older and had higher incidence rates of cardiovascular disease and acute kidney injury at admission, compared to nonusers. Inhospital mortality rates were significantly lower in the metformin-treated group, 56.8 % vs. 88.1 %, p <0.0001.
Though high lactate concentration indicates poor prognosis in septic patients, mortality rate was found to be significantly lower in those who were treated with metformin. This finding may help clinicians in deciding treatment for these patients, who could otherwise be considered too ill for real treatment benefit.
Patients with relapsed/refractory follicular lymphoma (R/R-FL) often require multiple treatment lines. We performed a phase 1b/2 single-center clinical trial of autologous point-of-care anti-CD19 ...chimeric antigen receptor (CAR) T-cells in R/R-FL patients treated patients with ≥ 2 treatment lines. All 26 patients enrolled received CAR T-cell infusion at a median of 11 days after leukapheresis. Seventy-seven percent of patients had POD24. At enrollment, disease stage was III-IV in 85% of the patients, 77% had high-risk FLIPI score, and 77% had progressive disease. Grade III-IV cytokine release and immune effector cell-associated neurotoxicity syndromes occurred in 12% and 16% of the patients, respectively. Overall response rate at 1-month was 88%. The median follow-up was 15.4 months. One-year overall and progression-free survival were 100% and 63%, respectively. In conclusion, point-of-care CAR T-cell, manufactured within 11 days, induced a high response rate with an acceptable safety profile in patients with high-risk R/R-FL.
Abstract β-Lactam–aminoglycoside combinations are commonly used despite lack of evidence of a clinical benefit. In this study, all randomised controlled trials (RCTs) assessing directly the clinical ...implications of synergism by comparing a β-lactam with the same β-lactam in combination with an aminoglycoside as empirical or definitive therapy for any type of infection and clinical scenario were compiled. A systematic search was undertaken to identify all trials regardless of language, date or publication status. The primary outcomes assessed were all-cause mortality and clinical failure regardless of antibiotic modifications. Risk of bias was evaluated and its effect was assessed through sensitivity analyses. Two reviewers applied inclusion criteria and extracted the data independently. A fixed-effect meta-analysis was performed. Fifty-two RCTs were identified assessing patients with febrile neutropenia, pneumonia, abdominal infections, bacteraemia, endocarditis or cystic fibrosis. Only five trials were double-blinded. All-cause mortality was similar with monotherapy versus combination therapy risk ratio (RR) = 0.96, 95% confidence interval (CI) 0.78–1.18, 28 trials, 3756 episodes. Clinical failure regardless of antibiotic modifications was not significantly different (RR = 0.88, 95% CI 0.74–1.05, 27 trials, 2500 episodes). Treatment failure including antibiotic addition/modification occurred more frequently with monotherapy (RR = 1.20, 95% CI 1.12–1.28, 48 trials, 6643 episodes). There were no significant differences with regard to bacterial or fungal superinfections or development of antibiotic-resistant strains. Combination therapy resulted in a significantly higher incidence of adverse events, mainly nephrotoxicity. Overall, no clinical benefit was found for the use of a β-lactam with an aminoglycoside compared with a β-lactam alone. Treatment with β-lactams as monotherapy entailed more antibiotic regimen modifications in open trials.
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