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Patients with FLT3-mutated AML have a high relapse rate and suboptimal outcomes. Many have co-mutations suitable for measurable residual disease (MRD) monitoring by RT-qPCR and those destined to relapse can be identified by high or rising levels of MRD, called molecular failure. This provides a window for pre-emptive intervention, but there is little evidence to guide treatment. The use of FLT3 inhibitors (FLT3i) appears attractive but their use has not yet been evaluated. We identified 56 patients treated with FLT3i at molecular failure. The FLT3 mutation was an ITD in 52, TKD in 7 and both in 3. Over half of patients had previously received midostaurin. Molecular failure occurred at a median 9.2 months from diagnosis and was treated with gilteritinib (n = 38), quizartinib (n = 7) or sorafenib (n = 11). 60% achieved a molecular response, with 45% reaching MRD negativity. Haematological toxicity was low, and 22 patients were bridged directly to allogeneic transplant with another 6 to donor lymphocyte infusion. 2-year overall survival was 80% (95%CI 69–93) and molecular event-free survival 56% (95%CI 44–72). High-sensitivity next-generation sequencing for FLT3-ITD at molecular failure identified patients more likely to benefit. FLT3i monotherapy for molecular failure is a promising strategy which merits evaluation in prospective studies.

Why did you do this work?Haematopoietic Stem Cell Transplant (HSCT) is used as a treatment for both malignant and non-malignant conditions. Conditioning is given prior to transplant to increase likelihood of engraftment and reduce risk of graft vs host disease (GvHD), this can be in the form of radiation, chemotherapy, or a combination of both.1 These conditioning regimens often lead to poor reproductive outcomes for both males and females.2 Fertility cryopreservation is a procedure carried out prior to HSCT in which the ovaries and testicular tissue in females and males respectively, are frozen so they can be re-transplanted later in life if fertility is an issue.What did you do?This is a retrospective study of male and female paediatric patients receiving fertility cryopreservation between 2020 and 2024 prior to an allogenic HSCT. A total of 28 boys and 29 girls were identified from a total of 186 patients who were transplanted during the selected period. Exclusion criteria included those travelling from overseas to receive treatment, apart from Republic of Ireland, patients receiving cryopreservation at another centre and those lacking documentation of the outcomes of the cryopreservation procedure. Patient notes were accessed, demographics noted and complications of cryopreservation were analysed. Patient age at cryopreservation ranged from 2 months to 16 years 4 months.What did you find?Both the numbers of males transplanted and fertility cryopreservation increased yearly during the trial period, however the percentage of boys undergoing cryopreservation increased at a faster rate, see figure 1. The rates in girls did not change , which is to be expected as cryopreservation is an established treatment in girls but not boys, meaning parents are less willing to consent to an experimental procedure. The main complication experienced post fertility cryopreservation surgery was pain which was experienced in 46% (n = 13) boys and 58% (n = 18) of girls. As demonstrated in figure 2, the length of time pain was experienced was usually shorter for female patients, when compared to male patients. Other complications included soft tissue injury, bleeding and wound infection – these were significantly more common in the male than the female cohorts.What does it mean?This audit highlights the rate of complications after fertility cryopreservation in paediatric patients is relatively high, however for the most part these were minor. It has shown that documentation of pain, bruising and any other complications should be assessed, treated and documented clearly. This data can be used to better inform families of what they may experience following a cryopreservation procedure so they are able to make more well informed decisions and reduce the anxiety they experience when complications occur.Abstract 7826 Figure 1%HSCT receiving fertility cryopreservation[Image Omitted. See PDF.]Abstract 7826 Figure 2Days complaining of pain[Image Omitted. See PDF.]ReferencesNagler A, Shimoni A. The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies, Chapter 13. 2019Wikander I, Lundberg FE, Nilsson H, Borgström, Rodriguez-Wallberg KA. A prospective study on fertility preservation in prepubertal and adolescent girls undergoing hematological stem cell transplantation. 2021 Jun 30.

The authors present a child with a rare case of unilateral pseudo-hypopyon and raised intraocular pressure as the only manifestation of acute lymphoblastic leukemia recurrence. This was treated with intravitreal methotrexate and chimeric antigen receptor T-cell therapy (CAR-T) with subsequent remission. This case demonstrates intravitreal methotrexate is a safe and effective adjunct to use with CAR-T therapy for relapsing acute lymphoblastic leukemia with ocular involvement. Further research should be sought on both CAR-T therapy and intravitreal methotrexate for acute lymphoblastic leukemia with ocular involvement. [J Pediatr Ophthalmol Strabismus. 2025;62(2):e18–e21.]

Abstract Introduction We report a multicentric experience of the relationship between ciclosporin exposure and time to relapse in a large homogenous cohort of paediatric AML patients receiving a T-replete cord blood transplant(TRCBT), adjusted to pre-transplant MRD and GVHD. Objectives The primary endpoint was time to relapse, and its relationship between ciclosporin AUC, use of additional immunosuppressive treatment (IST) and its total duration was investigated by multivariate Cox regression analysis. Methods It is a retrospective study, analyzing data from 7 paediatric transplant centers in the UK on children who had a TRCBT for HR AML between 2013 and 2023. Case records were analyzed to get transplant characteristics, GVHD prophylaxis, trough ciclosporin levels in the first 8 weeks and the transplant outcomes including GVHD and IST used, relapse and transplant related mortality (TRM). Results The cohort included 124 patients, 66 were MRD-positive pre-transplant, with a median follow up of 737.1 days (range:24-3540 days). The mortality rate was 40.7% and three-quarters occurred in the MRD-positive group. The median time to relapse was 180 days (range: 32 to 949). TRM was 13% and was the most prominent cause of mortality in MRD-negative group.The RFS is greater in MRD-negative group without severe aGVHD than in those with severe aGVHD, though not statistically significant. The RFS is significantly lower in the MRD-positive group without severe aGVHD than in those with it. The COX proportional hazards model using 95% CI confirmed a significant inverse relationship of AUC of Ciclosporin in the first 8 weeks on the time to relapse (p<0.02) and such a significant relationship maintained even after adjusting for the MRD status (p<0.03) and the presence of severe aGVHD (p<0.016). There was a significant inverse relationship between duration of CNI and time to relapse (p<0.03). The study did not find any effect of IST or its duration on time to relapse (p=0.567 and p=0.241 respectively). Discussion This is the largest homogenous cohort of TRCBT in AML investigating the role of ciclosporin prophylaxis on relapse. It confirms the importance of GVL effect and its relation to GVHD, particularly in MRD-positive patients as RFS is significantly better in those who experience aGVHD. Figure 1: Relapse free survival of different sub groups stratified based on MRD and severe aGVHD

Abstract Introduction Refractory and post-transplant relapsed Acute Leukaemia remain difficult to cure. Third-party pooled granulocytes induce massive, transient, donor-derived T-cell expansion after Cord Blood (CB) transplant. These expanded T-cells are cytotoxic, memory CD8, in contrast to the infused graft T-cells which are predominantly naïve CD4, and appear a priori candidate anti-tumour T-cells. Objectives In our prospective clinical trial, GRANS study (NCT05425043), we have given granulocytes peri-transplant with T-replete, deliberately mismatched CB to enhance the graft-versus-leukaemia effect of the transplant, in those with either primary refractory or relapsed/ refractory paediatric acute leukaemia. Here we report outcomes of all patients treated with this approach, including trial and off-trial patients. Methods Case records were analysed and data collected about patients’ demographics, transplant and donor characteristics and the outcomes including engraftment, acute and chronic GVHD, relapse and transplant related mortality. All patients (n=25) were given 7 daily doses of granulocytes starting from D-1. Immune suppression was withdrawn early. Results The granulocytes are well tolerated, no grade 3 or 4 CRS was encountered. There is increased graft rejection (seen in 4 patients) compared to a cohort of T-replete cord blood transplants in children with haematologic malignancy. In those that reject, then there is always residual leukaemia present. 2 of these patients successfully engrafted after a second CBT. Low severe aGVHD. Only 12% (n=3) developed severe aGVHD, despite early withdrawal of immunosuppression. No cGVHD was seen. Treatment related mortality is low, and 2 patients died, one with severe VOD and one with disseminated, aciclovir-resistant HSV infection. In those that do not reject the graft, all but one patient became MRD negative. In some, there is later relapse (n=7).The OS and the EFS were 56% (n=14) and 48% (n=12) respectively. Discussion The rates of aGVHD are tolerable, there is no cGVHD and the TRM is remarkably low, despite the mismatched graft. There is a higher graft failure rate and in those that do not experience GF, the remission rates are high but some patients relapse. In our next protocol, we plan to use an expanded CB to reduce GF, and cord derived DLI after cessation of immune suppression to reduce late relapse. Figure 1: Relapse free survival of different sub groups stratified based on MRD and severe aGVHD

\"Faith, and I'm tired of being maidenly,\" said Prudence Graham. She walked sedately to her room, bolted the door, and flung herself on the smooth bedspread. She shook her brown curls out around her shoulders, when she had removed her proper Quaker bonnet.

Purpose The purpose of this study is to review recent work in the robotics literature and identify future opportunities for consumer/tourist experience research in human-robot interactions (HRIs). Design/methodology/approach The paper begins by covering the framework of robotic agent presence and embodiment that are relevant for HRI. Next, the paper identifies future opportunities for hospitality and tourism scholars to undertake consumer/tourist experience research in HRIs. Findings The result of this study provided potential directions for advancing theoretical, methodological and managerial implications for tourism experience research in HRI. Research limitations/implications Concepts from robotics research are diffusing into a range of disciplines, from engineering to social sciences. These advancements open many unique, yet urgent, opportunities for hospitality and tourism research. Practical implications This paper illustrates the speed at which robotics research is progressing. Moreover, the concepts reviewed in this research on robotic presence and embodiment are relevant for real-world applications in hospitality and tourism. Social implications Developments in robotics research will transform hospitality and tourism experiences in the future. Originality/value This research is one of the early papers in the field to review robotics research and provide innovative directions to broaden the interdisciplinary perspective for future hospitality and tourism research.