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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 Anthracycline-treated childhood cancer survivors are at higher risk of cardiotoxicity, especially with cumulative doses received above 250 mg/m2. Dexrazoxane is the only option recommended for cardiotoxicity prevention in high-risk patients supported by randomised trials but its cost-effectiveness in paediatric cancer patients has not been established. Methods A cost-effectiveness model applicable to different national healthcare system perspectives, which simulates 10,000 patients with either sarcoma or haematologic malignancies, based upon baseline characteristics including gender, age at diagnosis, cumulative anthracycline dose and exposure to chest irradiation. Risk equations for developing congestive heart failure and death from recurrence of the original cancer, secondary malignant neoplasms, cardiac death, pulmonary death, and death from other causes were derived from published literature. These are applied to the individual simulated patients and time until development of these events was determined. The treatment effect of dexrazoxane on the risk of CHF or death was based upon a meta-analysis of randomised and non-randomised dexrazoxane studies in each tumour type. The model includes country specific data for drug and administration costs, all aspects of heart failure diagnosis and management, and death due to different causes for each of the five countries considered; France, Germany, the UK, Italy, and Spain. Results Dexrazoxane treatment resulted in a mean QALY benefit across the five countries ranging from 0.530 to 0.683 per dexrazoxane-treated patient. Dexrazoxane was cost-effective for paediatric patients receiving anthracycline treatment for sarcoma and for haematologic malignancies, irrespective of the cumulative anthracycline dose received. The Incremental Cost Effectiveness Ratio (ICER) was favourable in all countries irrespective of anthracycline dose for both sarcoma and haematological malignancies (range: dominant to €2196). Individual ICER varied considerably according to country with dominance demonstrated for dexrazoxane in Spain and Italy and ratios approximately double the European average in the UK and Germany. Conclusions Dexrazoxane is a highly cost-effective therapy for the prevention of anthracycline cardiotoxicity in paediatric patients with sarcoma or haematological malignancies in Europe, irrespective of the healthcare system in which they receive treatment. These benefits persist when patients who receive doses of anthracycline > 250 mg/m2 are included in the model.

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

Objective Bone marrow aspiration and lumbar puncture play essential roles in the diagnosis and treatment of haematological disorders. These repeated invasive procedures lead to considerable pain and stress in children, which is emotionally stressful for their parents. This study aimed to compare the effectiveness and outcomes of two combinations of midazolam-ketamine (MK) and propofol-sufentanil (PS) in painful procedures of children with haematologic malignancy. Methods In this prospective, randomised, double-blind clinical trial, we enrolled 80 eligible patients with haematologic malignancy aged 2-14 years. We randomly allocated them to the MK and PS groups. We recorded and compared the level of sedation, pain severity, hemodynamic indices, the onset of effect, duration of recovery and complications during and after procedure in the two groups. We analysed the data using the SPSS software. We used Mann-Whitney U, independent t-test, chi-square and Fisher's exact tests to compare continuous and categorical variables. Results From initially enrolled patients, 68 patients completed the study (38 in PS and 30 in MK group). The levels of sedation and the mean score of pain intensity were significantly lower in the MK group than those in the PS group (p

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

Carcinomatous Polyarthritis (CP) is defined as the development of arthritis in association with a malignancy but distinct from that associated with metastasis or direct invasion. It can occur before, with, or after onset of malignancy or with treatment. CP usually affects large joints and is negative for Anti Citrullinated Protein Antibodies (ACPA). CP is rarely if ever considered in the differential diagnosis of a case of symmetric polyarthritis with ACPA positivity. Presence of autoimmune disease related antibodies further obscures the diagnosis. We present a case of a young lady with symmetrical inflammatory polyarthritis with positive ACPA who was found to have haematological malignancy. This is one of the very few cases of CP of small joints with ACPA positivity reported worldwide and highlights the need to be vigilant for red flags while evaluating any case presenting with rheumatologic symptoms.

Modern-day treatment for the malignant lymphomas has resulted in an improved remission rate and survival. However, in the longer run, many of these regimens are associated with a significant incidence of secondary haematologic malignancies. This study further defines this occurrence. The records from 2196 consecutive patients with lymphoreticular neoplasms were retrospectively reviewed. In each case management was on a standard chemotherapy or irradiation protocol, approved by institutional review committees, and based on histopathology coupled with clinical stage at presentation. Diagnosis of myelodysplasia or acute leukaemia was made according to the French-American-British (FAB) criteria. From 1970 to 1990, 475 individuals with Hodgkin's Disease, and a further 1721 with other malignant lymphomas, were treated. Myelodysplasia developed in 4, acute myeloblastic leukaemia in 6, possible acute lymphoblastic leukaemia in 1 and, in the remaining case, precise characterization was not possible. Of these twelve patients, comprising 0.5% of the study cohort, 5 (1.1%) had Hodgkin's Disease and seven (0.4%) other lymphoreticular tumours. The median age was sixty-eight (range 33 to 81) years; seven were male. The median latent period from therapy to onset of the secondary neoplasms was 5.6 years (range 1-15.6). Treatment was possible in four of the twelve: two achieved complete remission but relapsed, two had only partial response. None survived fourteen months. Although the incidence is small, it is again noteworthy that all but one of the patients had received alkylating agents and this re-emphasizes the need to develop effective regimens with Jess carcinogenic potential.

Background There is scarcity of data regarding significance of candiduria in patients with hematologic malignancies and its association with invasive candidiasis.

Summary What is known and Objective: 6-Cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridone (ciclopirox) and specifically its olamine salt 6-cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridone 2-aminoethanol salt (ciclopirox olamine) are anti-fungal agents currently used for the treatment of mild to moderate cutaneous fungal infection. Our objective is to comment on the opportunity to rapidly reposition ciclopirox and its olamine for the treatment of haematologic malignancy by leveraging its prior published toxicology and pharmacology data. Comment: Ciclopirox olamine chelates intracellular iron and displays preclinical efficacy in the treatment of haematologic malignancy. Currently, an ongoing study is evaluating topical ciclopirox olamine for the treatment of cervical cancer. Doses of ciclopirox olaine required for a systemic anti-cancer effect appear pharmacologically achievable. However, caution is required as at the highest doses tested in animal toxicology studies, irreversible cardiac degeneration was observed. What is new and Conclusion: The existing pharmacology and toxicology data suggest that systemic ciclopirox olamine could be repositioned as a new investigational anti-cancer agent. The available pharmacology and toxicology data should aid in the design of phase I clinical trials of this agent in patients with refractory haematologic malignancies.

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.

Acute lymphoblastic leukaemia (ALL) presenting as peripheral blood hypereosinophilia is very rare and the incidence is

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

WOS: 000321226500028, Aim: H1N1 influenza virus infections in immunosuppressive patients cause complications. Clinical and laboratory findings of H1N1 positive haematology patients were evaluated in this study. Materials and methods: The "H1N1 Swine Influenza Suspicious Case Notification Form and Inpatient Follow-up Form" was prepared for 15 patients with suspected H1N1 infection between October 2009 and May 2010. H1N1 was detected by real-time RT-PCR assay. For all cases medical records were reviewed for clinical, demographic, and haematologic information. Results: H1N1 positivity was confirmed using real-time RT-PCR in 9 out of 15 patients (11 men, 4 women). One of the 9 patients had been followed up due to aplastic anaemia, 1 due to Evans syndrome, and the remaining 7 due to haematologic malignancy. Among the 9 patients diagnosed with H1N1,3 had previously undergone autologous haemopoietic stem cell transplantation (HSCT). H1N1 was detected in HSCT recipients in the early post-transplant period (range 7-21 days). The most prominent symptoms were as follows: high fever, cough, vomiting, nausea, and diarrhoea, in descending order. Oseltamivir was given to all patients. Eight patients responded to the treatment and recovered clinically. One patient (57-year-old female with multiple myeloma), required intensive care and she died due to severe sepsis and pneumonia. Conclusion: Our data show that subjective findings like headache and fatigue often seen in influenza infections were not the dominant clinical presentation in these patients. These infections should be considered in patients with haematological malignancy, and appropriate treatment and prophylaxis should be started early.

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.

Summarization: Acute Myeloid Leukaemia (AML) is a haematologic malignancy. Despite of improvements in prognosis it is still a severe disease and only a minority of patients are cured. Recently, insights into specific cytogenetics and biological aberration involved in the leukaemogenesis process are the target of research. LAM-99P GIMEMA Protocol identifies treatment guidelines for AML in adults. A methodological approach is proposed, compounding different modelling techniques, to assess the prognostic relevance of clinical as well as biological markers with regard to clinical endpoint, such as the achievement of Complete Remission in the short-term and long-term survival taking into account competing risks. Παρουσιάστηκε στο: International Journal of Biomedical Engineering and Technology