Outcomes for paediatric haematopoletic stem cell transplant patients following intensive care admission

The role of intensive care in the paediatric stem cell transplant (SCT)patient remains a highly controversial issue. Due to poor survival outcomes (discharge survival rates as low as 28.6% in patients admitted with lung disease) intensivists are often unwilling to admit SCT patients. However, recent studies have revealed that survival rates in children given intensive support are increasing with earlier admission to the paediatric intensive care unit (PICU), improved ventilation strategies, and earlier and better renal replacement therapy. We report the experience of patients from our institution who were admitted to the PICU following haematopoeitic SCT

Antimicrobial susceptibility of blood culture isolates of viridans streptococci: relationship to a change in empirical antibiotic therapy in febrile neutropenia

This study investigated the antibiotic susceptibilities of 67 isolates of viridans streptococci from 61 cases of bacteraemia in immunocompromised paediatric patients with malignancy. The majority of patients (87%) had received prior courses of empirical antibiotic therapy, which consisted of ceftazidime plus amikacin during period 1 and piperacillin/tazobactam plus amikacin during period 2. Susceptibility to vancomycin and quinupristin/dalfopristin was 100%. Susceptibility to ß-lactam antibiotics varied. For period 1, the geometric mean MICs of all ß-lactams tested against blood culture isolates (n = 31) exceeded those against isolates (n = 36) collected from blood after the change in empirical therapy (by 3.3-fold for ceftazidime, 2.8-fold for piperacillin/tazobactam and 1.6-fold for penicillin). The selection of a ß-lactam antibiotic for empirical therapy must be made with care, as repeated courses of certain agents may be more likely to select for viridans streptococci with diminished susceptibility

Zeros of conformal vector fields and twistor spinors in Lorentzian geometry

We study the zero set of conformal vector fields on Lorentzian manifolds that have properties like the associated conformal vector field of a twistor spinor. We prove that locally the zero set of such conformal vector fields lies on a lightlike smooth geodesic. (orig.)Available from TIB Hannover: RR 1596(439) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Results of a randomized trial in children with Acute Myeloid Leukaemia: Medical Research Council AML12 trial

The Medical Research Council Acute Myeloid Leukaemia 12 (MRC AML12) trial (children) addressed the optimal anthracenedione/anthracycline in induction and the optimal number of courses of consolidation chemotherapy. 504 children (<16 years) with AML were randomized between mitoxantrone/cytarabine/etoposide or daunorubicin/cytarabine/etoposide as induction chemotherapy and 270 entered a second randomization between a total of four or five courses of treatment. Ten-year event-free (EFS) and overall survival (OS) was 54% and 63% respectively; the relapse rate was 35%. There was no difference in complete remission rate between the induction regimens, but there was a benefit for mitoxantrone with regard to relapse rate [32% vs. 39%; Hazard ratio (HR) 0·73; 95% confidence interval (CI) 0·54, 1·00] and disease-free survival (DFS; 63% vs. 55%; HR 0·72; 95% CI 0·54, 0·96). However, this did not translate into a better EFS or OS (HR 0·84; 95% CI 0·63, 1·12). Results of the second randomization did not show a survival benefit for a fifth course of treatment (HR 1·01; 95% CI 0·63, 1·62), suggesting a ceiling of benefit for conventional chemotherapy and demonstrating the need for new agents. EFS was superior compared to the preceding trial AML10, partly due to fewer deaths in remission, highlighting the importance of supportive care

Acute myeloid leukaemia niche regulates response to L-asparaginase

Eradicating the malignant stem cell is the ultimate challenge in the treatment of leukaemia. Leukaemic stem cells (LSC) hijack the normal haemopoietic niche, where they are mainly protected from cytotoxic drugs. The anti‐leukaemic effect of L‐asparaginase (ASNase) has been extensively investigated in acute lymphoblastic leukaemia, but only partially in acute myeloid leukaemia (AML). We explored the susceptibility of AML‐LSC to ASNase as well as the role of the two major cell types that constitute the bone marrow (BM) microenvironment, i.e., mesenchymal stromal cells (MSC) and monocytes/macrophages. Whilst ASNase was effective on both CD34+CD38+ and CD34+CD38− LSC fractions, MSC and monocytes/macrophages partially counteracted the effect of the drug. Indeed, the production of cathepsin B, a lysosomal cysteine protease, by BM monocytic cells and by AML cells classified as French‐American‐British M5 is related to the inactivation of ASNase. Our work demonstrates that, while MSC and monocytes/macrophages may provide a protective niche for AML cells, ASNase has a cytotoxic effect on AML blasts and, importantly, LSC subpopulations. Thus, these features should be considered in the design of future clinical studies aimed at testing ASNase efficacy in AML patients