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We report the cases of 10 patients with oral squamous cell carcinoma (SCC) post-haematopoietic stem cell transplant (HSCT). Median latency from HSCT to oral SCC diagnosis was 10 years (range: 4-17 years), with 90% (9/10) reporting a history of chronic graft-versus-host disease (cGVHD) and 40% (4/10) exhibiting active severe manifestations of oral GvHD. Clinical findings at diagnosis included induration, ulceration, tenderness, bleeding, hyperkeratosis, speckling and lymphadenopathy. The tongue and buccal mucosa were the most common sites affected. The disease stage at presentation ranged from T1N0M0 to T4N2M0. Management included surgical resection in 90% (9/10) of patients with or without chemotherapy and/or radiotherapy. The median follow-up for the cohort was 1 year, with a 50% (5/10) mortality rate. SCC-specific mortality was 30% (3/10). Our data highlight the importance of regular, active oral and cutaneous surveillance of patients post-HSCT in specialized dermatology clinics, irrespective of GvHD severity and length of iatrogenic immunosuppression., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

HLA matching is a critical factor in allogeneic unrelated hematopoietic cell transplantation (HCT) because of its impact on post-transplantation survival and quality of life. Umbilical cord blood transplantation (UCBT) offers unique advantages, but determining the optimal approach to graft selection and immunosuppression remains challenging. Unsupervised clustering, a machine learning technique, has potential for analyzing transplantation outcomes, but its application in investigating leukemia outcomes has been limited. This study aimed to identify optimal combinations of HLA/ killer immunoglobulin receptor (KIR) donor-patient pairing, conditioning, and immunosuppressive regimens in pediatric patients with acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML) undergoing UCBT. Outcome data for single, unmanipulated UCBT in pediatric AML (n = 708) and ALL (n = 1034) patients from the Eurocord/EBMT registry were analyzed using unsupervised clustering. Resulting clusters were used to inform post hoc competing risks and Kaplan-Meier analyses. In AML, single HLA-C mismatches with other loci fully matched (7/8) were associated with poorer relapse-free survival (RFS) (P = .039), but a second mismatch at any other locus counteracted this effect. In ALL, total body irradiation (TBI) effectively prevented relapse mortality (P = .007). KIR/HLA-C match status affected RFS in AML (P = .039) but not in ALL (P = .8). Administration of antithymocyte globulin (ATG) substantially increased relapse, with no relapses occurring in the 85 patients who did not receive ATG. Our unsupervised clustering analyses generate several key statistical and mechanistic hypotheses regarding the relationships between HLA matching, conditioning regimens, immunosuppressive therapies, and transplantation outcomes in pediatric AML and ALL patients. HLA-C and KIR combinations significantly impact RFS in pediatric AML but not in ALL. ATG use in fully matched pediatric patients is associated with late-stage relapse. TBI regimens appear to be beneficial in ALL, with efficacy largely independent of histocompatibility variables. These findings reflect the distinct genetic and biological profiles of AML and ALL., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

A woman who had undergone haematopoietic stem cell transplantation presented with cutaneous features suggestive of graft-versus-host disease. Histopathological examination revealed a diffuse dermal infiltration of atypical monomorphic cells with a high proliferative index. Immunohistochemistry revealed positivity for monocytic markers, but negativity for T-cell markers., (© 2022 British Association of Dermatologists.)

Allogeneic haematopoietic stem cell transplant (HSCT) recipients remain at high risk of adverse outcomes from coronavirus disease 2019 (COVID-19) and emerging variants. The optimal prophylactic vaccine strategy for this cohort is not defined. T cell-mediated immunity is a critical component of graft-versus-tumour effect and in determining vaccine immunogenicity. Using validated anti-spike (S) immunoglobulin G (IgG) and S-specific interferon-gamma enzyme-linked immunospot (IFNγ-ELIspot) assays we analysed response to a two-dose vaccination schedule (either BNT162b2 or ChAdOx1) in 33 HSCT recipients at ≤2 years from transplant, alongside vaccine-matched healthy controls (HCs). After two vaccines, infection-naïve HSCT recipients had a significantly lower rate of seroconversion compared to infection-naïve HCs (25/32 HSCT vs. 39/39 HCs no responders) and had lower S-specific T-cell responses. The HSCT recipients who received BNT162b2 had a higher rate of seroconversion compared to ChAdOx1 (89% vs. 74%) and significantly higher anti-S IgG titres (p = 0.022). S-specific T-cell responses were seen after one vaccine in HCs and HSCT recipients. However, two vaccines enhanced S-specific T-cell responses in HCs but not in the majority of HSCT recipients. These data demonstrate limited immunogenicity of two-dose vaccination strategies in HSCT recipients, bolstering evidence of the need for additional boosters and/or alternative prophylactic measures in this group., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Graft-versus-host disease (GVHD) is a significant cause of morbidity and mortality following allogeneic stem cell transplantation. These patients face unique challenges due to the complexity of GVHD which can affect multiple organ systems, and the toxicity of treatments. Despite the known impact on quality of life (QOL), qualitative data within the bone marrow transplantation (BMT) literature is rare, and there has been no qualitative work exploring patient experience of specialist healthcare provision for GVHD in the United Kingdom., Methods: We conducted a primary explorative qualitative study of the experience of QOL issues and multidisciplinary care in patients with chronic GVHD following allogeneic stem cell transplantation. Eight patients were identified using convenience sampling from specialist BMT outpatient clinics. Following consent, patients were interviewed individually via telephone. Transcripts of interviews were analyzed using an inductive thematic approach., Results: Mean participant age was 61-years-old (range 45-68), with a mean time post-transplant of 3 years at time of interview (range 3 months-15 years). Five key QOL themes were identified: (1) 'Restricted as to what I can do'; (2) Troubling symptoms-'you can sort of get GVHD anywhere'; (3) Confusion/uncertainty over GVHD symptoms-'Is this the GVHD?'; (4) Unpredictable course and uncertainty about the future; and (5) Adapting to the sick role. In addition, four themes related to experience of service provision were identified: (1) personal care and close relationship with BMT nurses; (2) efficiency versus long waits-'On the case straight away'; (3) information provision-'went into it with a bit of a rosy view'; and (4) the role of support groups., Conclusions: These qualitative data reflect the heterogeneity of experiences of the GVHD patient population, reflecting the need for a flexible and nuanced approach to patient care with emphasis on comprehensive information provision. We have identified the key role that BMT specialist nurses within the multidisciplinary team play in supporting patients. We advocate future research should focus on ways to meet the complex needs of this patient group and ensure that the personal care and close relationships are not lost in service redesigns embracing remote consultations.

Outcomes in acute myeloid leukemia (AML) are dependent on patient- and disease-characteristics, treatment, and socioeconomic factors. AML outcomes between resource-constrained and developed countries have not been compared directly. We analyzed two cohorts: from São Paulo state, Brazil (USP, n  = 312) and Oxford, United Kingdom (OUH, n  = 158). USP cohort had inferior 5-year overall survival compared with OUH (29% vs. 49%, adjusted- p =.027). USP patients have higher early-mortality (23% vs. 6% p <.001) primarily due to multi-resistant Gram-negative bacterial and fungal infections. USP had higher 5-year cumulative incidence of relapse (60% vs. 50%, p =.0022), were less likely to undergo hematopoietic stem cell transplant (HSCT) (28% vs. 75%, p <.001) and waited longer for HSCT (median, 23.8 vs. 7.2 months, p <.001). Three-year survival in relapsed patients was worse in USP than OUH (10% vs. 39%, p <.001). Our study indicates that efforts to improve AML outcomes in Brazil should focus on infection prevention and control, and access to HSCT.

To obtain a qualitative as well as quantitative view immune reconstitution following umbilical cord blood (UCB) transplantation of paediatric patients, we utilised a broad panel of flow cytometry markers to monitor the phenotypes of lymphoid and myeloid cells at 1-12 months post-transplant. Samples were received from 46 patients with a median age of 3.3 years and survival was 76% at 1 year. Monocytes were at similar or higher median levels than in adult controls at all times tested, with a high CD16+ proportion in the first 3 months. NK cells were also within adult ranges, with a CD56++ high proportion in the first 6 months. B cell recovery was seen from 2 months in most patients and T cells from 3 months, both were delayed with anti-thymocyte globulin (ATG) treatment. CD4:CD8 ratios were high in the first 6 months, and the proportion of T cells with recent thymic emigrant and naïve phenotypes rose from 3 months. NK and plasmacytoid dendritic cell numbers remained at reduced levels in patients not surviving to 1 year. Our results can serve as a useful reference for detailed monitoring of immune reconstitution in paediatric recipients of UCB., (© 2020 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

The control of peripheral immune responses by FOXP3 + T regulatory (Treg) cells is essential for immune tolerance. However, at any given time, Treg frequencies in whole blood can vary more than fivefold between individuals. An understanding of factors that influence Treg numbers and migration within and between individuals would be a powerful tool for cellular therapies that utilize the immunomodulatory properties of Tregs to control pathology associated with inflammation. We sought to understand how season could influence Treg numbers and phenotype by monitoring the proportion of natural thymus-derived Tregs (nTregs) defined as (CD3 + CD4 + CD25 + FOXP3 + CD127 -/lo w ) cells as a proportion of CD4 + T cells and compared these to all FOXP3 + Tregs (allTregs, CD3 + CD25 + FOXP3 + CD127 -/lo w ). We were able to determine changes within individuals during 1 year suggesting an influence of season on nTreg frequencies. We found that, between individuals at any given time, nTreg/CD4 + T cells ranged from 1.8% in February to 8.8% in the summer where median nTreg/CD4 in January and February was 2.4% (range 3.75-1.76) and in July and August was 4.5% (range 8.81-3.17) p = 0.025. Importantly we were able to monitor individual nTreg frequencies throughout the year in donors that started the year with high or low nTregs. Some nTreg variation could be attributed to vitamin D status where normal linear regression estimated that an absolute increase in nTreg/CD4 + by 0.11% could be expected with 10 nmol increase in serum 25 (OH) vitamin D3 ( p = 0.005, 95% CI: 0.03-0.19). We assessed migration markers on Tregs for the skin and/or gut. Here cutaneous lymphocyte associated antigen (CLA + ) expression on CD25 + FOXP3 + CD4 + /CD4 + was compared with the same population expressing the gut associated integrin, β7. Gut tropic CD25 + FOXP3 + β7 + Tregs/CD4 + had similar dynamics to nTreg/CD4 + . Conversely, CD25 + FOXP3 + CLA + Tregs/CD4 + showed no association with vitamin D status. Important for cellular therapies requiring isolation of Tregs, the absolute number of β7 + CD4 + CD25 + FOXP3 + Tregs was positively associated with 25(OH)vitamin D3 ( R 2 = 0.0208, r = 0.184, p = 0.021) whereas the absolute numbers of CLA + CD4 + CD25 + FOXP3 + Tregs in the periphery were not influenced by vitamin D status. These baseline observations provide new opportunities to utilize seasonal variables that influence Treg numbers and their migratory potential in patients or donors., (Copyright © 2020 Lamikanra, Tsang, Elsiddig, Spencer, Curnow, Danby and Roberts.)