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Optimal post-remission therapy for adolescents and young adults (AYAs) with Ph-negative acute lymphoblastic leukemia (ALL) in first complete remission (CR1) is not established. We compared overall survival (OS), disease-free survival (DFS), relapse, and non-relapse mortality (NRM) for patients receiving post-remission therapy on CALGB 10403 to a cohort undergoing myeloablative (MA) allogeneic hematopoietic cell transplantation (HCT) in CR1. In univariate analysis, OS was superior with chemotherapy compared to MA allogeneic HCT (3-year OS 77% vs. 53%, P  < 0.001). In multivariate analysis, allogeneic HCT showed inferior OS (HR 2.00, 95% CI 1.5–2.66, P  < 0.001), inferior DFS (HR 1.62, 95% CI 1.25–2.12, P  < 0.001), and increased NRM (HR 5.41, 95% CI 3.23–9.06, P  < 0.001) compared to chemotherapy. A higher 5-year relapse incidence was seen with chemotherapy compared to allogeneic HCT (34% vs. 23%, P  = 0.011). Obesity was independently associated with inferior OS (HR 2.17, 95% CI 1.63–2.89, P  < 0.001), inferior DFS (HR 1.97, 95% CI 1.51–2.57, P  < 0.001), increased relapse (1.84, 95% CI 1.31–2.59, P  < 0.001), and increased NRM (HR 2.10, 95% CI 1.37–3.23, P  < 0.001). For AYA ALL patients in CR1, post-remission therapy with pediatric-style chemotherapy is superior to MA allogeneic HCT for OS, DFS, and NRM.

Both Noonan syndrome and juvenile myelomonocytic leukemia are characterised by hyperactivation of the Ras/ MAPK signalling pathway, and as such may manifest concurrently. Here, we report a case study involving twins who originally presented with a petechial rash and a marked thrombocytopenia. Over time, the haematological picture developed into a juvenile myelomonocytic leukemia, and given the rare nature of this disorder, prompted review for other clinical manifestations, thus ultimately allowing the haematologist to consider a syndromic disorder. Key words: Juvenile myelomonocytic leukaemia, Noonan syndrome, Ras/MAPK signalling pathway.

Bacterial bloodstream infections (BSI) can be a substantial contributor to complications of GVHD treatment. The aim of this study was to determine the risk for BSI from neutrophil engraftment through day 100 post transplant in patients with acute GVHD (AGVHD) based on organ involvement and severity. Patients ( n  = 4064) who underwent an allogeneic hematopoietic stem cell transplant (HCT) reported to the CIBMTR registry were analyzed. Grade II-IV AGVHD occurred in 1607 (39.5%) patients and was associated with a greater day-100 incidence of post engraftment BSI than with grade 0/I (24.9 vs. 15.3%). Patients with grade III/IV AGVHD had the highest BSI risk (HR 2.45; 95% CI 1.99–3.0; p  < 0.0001). Lower GI involvement increased BSI risk (HR 1.54; 95% CI 1.17–2.02; p  = 0.0019). BSI post-engraftment through day 100 was associated with worse survival (HR 1.64, 95% CI 1.43–1.87; p  < 0.001) and higher non-relapse mortality (NRM), (HR 2.22; 95% CI 1.91–2.59; p  < 0.001). Those with stage III/IV GI involvement are at highest risk for BSI. Future studies evaluating novel methods for preventing BSI in these high risk populations are needed to reduce mortality associated with AGVHD. Highlights Bacterial blood stream infections are more common in patients with Grade II-IV AGVHD with roughly 25% of these patients developing at least one BSI by day-100. Patients with grade III/IV AGVHD and those with lower gastrointestinal involvement are at the highest risk for BSI. Patients who experience a BSI by day 100 have worse survival and over a two-fold higher probability for non-relapse mortality.

Background There is a paucity of data on the role of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with angioimmunoblastic T-cell lymphoma (AITL). Using the CIBMTR registry, we report here the outcomes of AITL patients undergoing an allo-HCT. Methods We evaluated 249 adult AITL patients who received their first allo-HCT during 2000–2016. Results The median patient age was 56 years (range = 21–77). Majority of the patients were Caucasians (86%), with a male predominance (60%). Graft-versus-host disease (GVHD) prophylaxis was predominantly calcineurin inhibitor-based approaches while the most common graft source was peripheral blood (97%). Median follow-up of survivors was 49 months (range = 4–170 months). The cumulative incidence of grade 2–4 and grade 3–4 acute GVHD at day 180 were 36% (95% CI = 30–42) and 12 (95% CI = 8–17), respectively. The cumulative incidence of chronic GVHD at 1 year was 49% (95%CI 43–56). The 1-year non-relapse mortality (NRM) was 19% (95% CI = 14–24), while the 4-year relapse/progression, progression-free survival (PFS), and overall survival (OS) were 21% (95% CI = 16–27), 49% (95% CI = 42–56), and 56% (95% CI = 49–63), respectively. On multivariate analysis, chemoresistant status at the time of allo-HCT was associated with a significantly higher risk for therapy failure (inverse of PFS) (RR = 1.73 95% CI = 1.08–2.77), while KPS < 90% was associated with a significantly higher risk of mortality (inverse of OS) (RR = 3.46 95% CI = 1.75–6.87). Conclusion Our analysis shows that allo-HCT provides durable disease control even in AITL patients who failed a prior auto-HCT and in those subjects with refractory disease at the time of allografting.

The thermodynamic properties of Schwarzschild-anti-de Sitter black holes confined within finite isothermal cavities are examined. In contrast to the Schwarzschild case, the infinite cavity limit may be taken which, if suitably stated, remains double valued. This allows the correspondence between non-existence of negative modes for classical solutions and local thermodynamic stability of the equilibrium configuration of such solutions to be shown in a well defined manner. This is not possible in the asymptotically flat case. Furthermore, the non-existence of negative modes for the larger black hole solution in Schwarzschild-anti-de Sitter provides strong evidence in favour of the recent positive energy conjecture by Horowitz and Myers.

Philadelphia chromosome-positive (Ph + ) acute lymphoblastic leukemia (ALL) in children and adolescents has, until recently, been considered one of the poorest-risk subgroups of ALL. With chemotherapy alone, only 20-30% of children with Ph + ALL are cured. Allogeneic hematopoietic cell transplantation in first complete remission cures 60% of patients with a closely matched donor. Although targeted tyrosine kinase inhibitors (TKIs) have limited activity against Ph + ALL as a single agent, they have been evaluated in combination with chemotherapy with promising results. The early results of Children's Oncology Group trial AALL0031 have shown 88% 3-year event-free survival for Ph + patients treated with intensive chemotherapy plus continuous-dosing imatinib. This suggests that chemotherapy plus TKIs may be the initial treatment of choice for Ph + ALL in children. However, the numbers are small in this trial and confirmatory results are not yet available from the European Intergroup Study on Post Induction Treatment of Philadelphia Positive Acute Lymphoblastic Leukaemia with Imatinib trial. Additional issues include determining the most effective TKI (imatinib, dasatinib or nilotinib) and the most effective, least toxic chemotherapy backbone. The experience of adding a targeted agent such as a TKI to the standard chemotherapy regimen suggests that this strategy might be applied to other ALL subtypes to achieve both increased efficacy and decreased toxicity.

Understanding the ecology of the gastrointestinal tract and the impact of the contents on the host mucosa is emerging as an important area for defining both wellness and susceptibility to disease. Targeted delivery of drugs to treat specific small intestinal disorders such as small bowel bacterial overgrowth and targeting molecules to interrogate or to deliver vaccines to the remote regions of the small intestine has proven difficult. There is an unmet need for methodologies to release probes/drugs to remote regions of the gastrointestinal tract in furthering our understanding of gut health and pathogenesis. In order to address this concern, we need to know how the regional delivery of a surrogate labeled test compound is handled and in turn, if delivered locally as a liquid or powder, the dynamics of its subsequent handling and metabolism. In the studies we report on in this paper, we chose 13 C sodium acetate ( 13 C-acetate), which is a stable isotope probe that once absorbed in the small intestine can be readily measured non-invasively by collection and analysis of 13 CO 2 in the breath. This would provide information of gastric emptying rates and an indication of the site of release and absorptive capacity. In a series of in vitro and in vivo pig experiments, we assessed the enteric-protective properties of a commercially available polymer EUDRAGIT® L100-55 on gelatin capsules and also on DRcaps®. Test results demonstrated that DRcaps® coated with EUDRAGIT® L100-55 possessed enhanced enteric-protective properties, particularly in vivo . These studies add to the body of knowledge regarding gastric emptying in pigs and also begin the process of gathering specifications for the design of a simple and cost-effective enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine.