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What is known and objectives Augmented renal clearance (ARC) is characterized by enhanced renal clearance, which leads to insufficient vancomycin exposure and treatment failure. In haematologic malignancy patients, determination of optimal vancomycin dosage is essential because of high stake of life-threatening bacterial infection and increased clearance. The aim of this study was to describe vancomycin pharmacokinetic parameters in haematologic malignancy with augmented renal clearance children and define the appropriate dosing regimen to achieve an AUC0-24h /MIC ≥400. Methods Hematologic malignancy with ARC children was enrolled in this retrospective study. The vancomycin PPK model was established by non-linear mixed-effects modelling programme. Goodness-of-fit (GOF) plots, non-parametric bootstrap, normalized prediction distribution error (NPDE) and visual predictive checks (VPCs) were carried out for internal evaluation of the final model. Monte Carlo simulation method was used to stimulate the optimal dosage regimens. Results Fifty-three patients with 106 samples were included. A one-compartment model with first-order elimination was developed, and the final model was as follows: CL (L/h) = 6.32×（WT/70）0.75 × e0.0467 ; V(L) = 39.6×(WT/70), where WT denotes weight (kg). The internal validation of the model showed a good prediction performance. Monte Carlo simulation results showed that when MIC was 0.5 mg/L or 1 mg/L, the recommended doses to achieve a target of AUC0-24h /MIC ≥400 were 25 to 40 and 50 to 75 mg/kg/d, respectively. With decreasing weight, the recommended dosage to achieve an AUC0-24h /MIC ≥400 increased. What is new and conclusion A one-compartment vancomycin PPK model was established in haematologic malignancy with augmented renal clearance children with weight with allometric scaling as a significant covariate. When MIC was 1 mg/L, current recommended paediatric dosages were insufficient in haematologic malignancy with augmented renal clearance children and should be increased.

BACKGROUND: Detection of galactomannan (GM) from bronchoalveolar lavage fluid (BALF) or serum is broadly used for diagnosis of invasive aspergillosis (IA), although the sensitivity of GM from serum is lower in non-neutropenic patients. We evaluated the Aspergillus galactomannan Lateral Flow assay (LFA) with digital readout from serum in a mixed cohort of patients. METHODS: We performed a retrospective two-centre study evaluating the LFA from serum of patients with clinical suspicion of IA obtained between 2015 and 2021 at the University of California San Diego and the Medical University of Graz. The sensitivity and specificity was calculated for proven/probable aspergillosis versus no aspergillosis. Correlation with same-sample GM was calculated using Spearman correlation analysis and kappa statistics. RESULTS: In total, 122 serum samples from 122 patients were analysed, including proven IA (n=1), probable IA or coronavirus-associated pulmonary aspergillosis (CAPA) (n=27), and no IA/CAPA/non-classifiable (n=94). At a 0.5 ODI cut-off, the sensitivity and specificity of the LFA was 78.6% and 80.5%. Spearman correlation analysis showed a strong correlation between serum LFA ODI and serum GM ODI (ρ 0.459, p&nbsp

BACKGROUND: Allogeneic haematopoietic cell transplantation (HCT) is often associated with poor oral intake due to painful mucositis and gastrointestinal sequalae that occur following a preparative regimen of intensive chemotherapy and/or total body radiation. Although attractive to assume that optimal nutrition improves HCT outcomes, there are limited data to support this. It is also unclear whether artificial nutrition support should be provided as enteral tube feeding or parenteral nutrition (PN). METHODS: We analysed day-100 non-relapse mortality (NRM), incidence of acute graft-versus-host disease (GvHD), acute gastrointestinal GvHD, 5-year survival and GvHD-free/relapse-free survival (GRFS) according to both route and adequacy of nutritional intake prior to neutrophil engraftment, together with other known prognostic factors, in a retrospective cohort of 484 patients who underwent allogeneic HCT for haematologic malignancy between 2000 and 2014. RESULTS: Multivariate analyses showed increased NRM with inadequate nutrition (hazard ratio (HR) 4.1; 95% confidence interval (CI) 2.2-7.2) and adequate PN (HR 2.9; 95% CI 1.6-5.4) compared to adequate enteral nutrition (EN) both P

BACKGROUND AND OBJECTIVES Practices in end-of-life platelet transfusions in haematologic malignancies are variable. Our aim was to describe the platelet transfusion burden and parameters linked to this indication in such a setting and thereby contribute to defining optimal practices. MATERIALS AND METHODS From July 2015 to December 2016, all consecutive deceased adult patients with a haematologic malignancy receiving a platelet transfusion in the last 6 months of their life from the Etablissement Francais du Sang Bourgogne Franche-Comte were included retrospectively. The outcome criteria were changes in the number of platelet transfusions, percent platelet recovery, platelet transfusion interval, reported bleeding with its grade and recipient adverse events in the last 6 months of life. RESULTS Among the 1125 patients monitored, 119 were included in our study. Bleeding prophylaxis (versus treatment) was the reason for 55% of transfusions. 18% of platelet concentrates (n = 1999) were transfused during the last two weeks of life. As death approached, the transfusion and haemorrhage burden increased (P

Multiple myeloma (MM) is a haematologic malignancy with significant improvements in the overall survival over the last decade. However, patients still relapse and die due to a lack of treatment options. Ultimately, novel therapies with the potential for long term remissions are needed for patients with advanced MM. Research efforts for such immune therapies were not successful until recently when the first immunotherapies for MM were approved in 2015 and many more are under development. In this review, we focus on adoptive cell therapies including CAR T-cell and CAR NK-cell therapies for patients with MM. We will provide an update on clinical and translational advances with a focus on results from ongoing clinical trials with BCMA targeted cellular therapies and the development of other novel targets, changes in the manufacturing process, trials focusing on earlier lines of therapy and combinations with other therapies as well as off the shelf products.

BACKGROUND Posaconazole (PCZ) is a triazole approved for prophylaxis of invasive fungal infections. OBJECTIVES Herein, the impact of clinical variables on PCZ plasma concentrations (PPCs) attained with PCZ delayed-release tablet (DRT) was investigated and compared with a historical cohort treated with PCZ oral suspension (OS). PATIENTS/METHODS Steady-state PCZ PPCs in 513 patients with haematologic malignancy treated with PCZ-DRT were assessed and impact of variables were analysed. Also, a comparison with matched historical cohort treated with PCZ-OS was made. RESULTS The median PPC in the PCZ-DRT group was 1,308.9 ng/mL (range: 29.8-10 455.9). Use of proton pump inhibitor (1181 vs 1344 ng/mL, P = .0337) in the AML/myelodysplastic syndrome remission induction group, diarrhoea (867 vs 1543 ng/mL, P = .0325) and gastrointestinal graft-versus-host disease (870 vs 1713 ng/mL, P = .0178) in the HSCT group were associated with lower PPCs. There was lack of evidence that hepatotoxicity was related with PCZ-DRT. Higher prevalence of UGT1A4*3 allele (33.0%) was noted compared to allele frequency in Koreans in those with PPCs

This prospective observational study examined the adherence to published European guidelines on erythropoiesis-stimulating agents (ESAs) and the pattern of use and effect of darbepoetin alfa (DA) 500 microg once every 3 weeks (Q3W) for the treatment of chemotherapy-induced anaemia (CIA).A total of 293 patients were included (263 solid tumour, 30 haematologic malignancy). Their mean age was 63 years, 51% were male, 57% had platinum-based chemotherapy. DA was started at a haemoglobin (Hb) level between 9 and 11 g/dL in 82% of patients.In an analysis correcting for transfusions, 55% of patients achievedor =2 g/dL increase in Hb, and a Hb level of11 g/dL was reached in 81%. Transfusion rate was 27%. Most patients (70%) were treated in a Q3W chemotherapy, and planned synchronisation of chemotherapy and Q3W DA could be maintained in 76%.Adherence to European guidelines for DA treatment was good, and Q3W DA treatment was in synchronisation with Q3W chemotherapy in the majority of the patients, thereby reproducing the findings of a recent phase III study.

The purpose of this study was to identify factors influencing mortality in neutropenic patients with haematologic malignancies or solid tumours with bloodstream infection (BSI). All episodes of BSI occurring in adult neutropenic patients with haematologic malignancies or solid tumours were prospectively recorded from January 2006 to December 2013. We analysed the factors influencing mortality in both groups of patients. We documented 602 consecutive episodes of BSI; 510 occurred in patients with haematologic malignancies and 92 in patients with solid tumours. The overall case-fatality rates were 12% and 36%, respectively. Independent risk factors associated with a higher case-fatality rate in patients with haematologic malignancies were: intensive care unit admission (odds ratio (OR), 15.2; 95% confidence interval (CI), 5.4–42.7), advanced neoplasm (OR, 8.7; 95% CI, 2.9–25.7), corticosteroid therapy (OR, 7.0; 95% CI, 3–16.4), multidrug-resistant Gram-negative BSI (OR, 3.8; 95% CI, 1.2–11.8) and a Multinational Association for Supportive Care in Cancer risk score of

In view of the poor outcomes associated with mucormycosis in patients with haematologic malignancies (HM) and haematopoietic cell transplant recipients, antifungal combinations are frequently used, yet the value of such strategy remains unclear. We reviewed the records of HM patients treated for mucormycosis from 1994 to 2014. The primary outcome was 6-week mortality after treatment initiation. Of the 106 patients identified, 44% received monotherapy and 56% received combination treatment as initial therapy. Six-week mortality was associated with disseminated mucormycosis (p 0.018), active malignancy (p 0.99). In the high-risk group (n = 57), 71% of monotherapy versus 61% of combination therapy patients died within 6 weeks (p 0.42). With the current status of mucormycosis diagnosis, there was no difference in mortality in HM patients, whether they received monotherapy or combination treatment as initial therapy. Earlier diagnosis and immune reconstitution are unmet needs to affect outcomes.