Publications
78 results found
Innes AJ, Ghani R, Mullish BH, et al., 2020, O105. Faecal microbiota transplant (FMT) can reduce the high NRM associated with multi-drug resistant organism (MDRO) colonisation prior to allogeneic HCT., The 46th Annual Meeting of the European Society for Blood and Marrow Transplantation, Publisher: Springer Nature [academic journals on nature.com], Pages: 122-122, ISSN: 0268-3369
Ellington MJ, Davies F, Jauneikaite E, et al., 2020, A multi-species cluster of GES-5 carbapenemase producing Enterobacterales linked by a geographically disseminated plasmid, Clinical Infectious Diseases, Vol: 71, Pages: 2553-2560, ISSN: 1058-4838
BACKGROUND: Early and accurate treatment of infections due to carbapenem-resistant organisms is facilitated by rapid diagnostics but rare resistance mechanisms can compromise detection. One year after a GES-5 carbapenemase-positive Klebsiella oxytoca infection was identified by whole genome sequencing (WGS) (later found to be part of a cluster of three cases), a cluster of 11 patients with GES-5-positive K. oxytoca was identified over 18 weeks in the same hospital.METHODS: Bacteria were identified by MALDI-TOF, antimicrobial susceptibility testing followed EUCAST guidelines. Ertapenem-resistant isolates were referred to Public Health England for characterization using PCR detection of GES, pulse-field gel electrophoresis (PFGE) and WGS for the second cluster.RESULTS: The identification of the first GES-5 K. oxytoca isolate was delayed, being identified on WGS. A GES-gene PCR informed the occurrence of the second cluster in real-time. In contrast to PFGE, WGS phylogenetic analysis refuted an epidemiological link between the two clusters; it also suggested a cascade of patient-to-patient transmission in the later cluster. A novel GES-5-encoding plasmid was present in K. oxytoca,E. coli and E. cloacae isolates from unlinked patients within the same hospital group and in human and wastewater isolates from three hospitals elsewhere in the UK.CONCLUSIONS: Genomic sequencing revolutionized the epidemiological understanding of the clusters, it also underlined the risk of covert plasmid propagation in healthcare settings and revealed the national distribution of the resistance-encoding plasmid. Sequencing results also informed and led to the ongoing use of enhanced diagnostic tests for detecting carbapenemases locally and nationally.
Claudiani S, Rosadas C, McClure M, et al., 2020, Prevalence of Sars-Cov-2 Infection in Patients with Chronic Myeloid Leukemia, Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
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- Citations: 8
Innes AJ, Cook LB, Marks S, et al., 2020, Ruxolitinib for tocilizumab-refractory severe COVID-19 infection., British Journal of Haematology, Vol: 190, Pages: e198-e200, ISSN: 0007-1048
Whilst the majority of patients with COVID-19 infection have mild self-limiting symptoms, for some the SARS-CoV2 virus can trigger a severe hyperinflammatory syndrome which is life threatening. Anti-IL6 therapy has shown promise in restraining the hyperinflammatory syndrome and while IL-6 is a pleiotropic mediatory of the inflammatory response, redundancy within inflammatory pathways means that the use of such targeted monoclonal therapy may have too restricted a repertoire in some patients. We present the case of a 53-year-old haematopoetic stem cell transplant recipient who developed a severe COVID-19 that was refractory to anti-IL6 therapy, but responded to Jak-Stat inhibition with ruxolitinib, demonstrating its safety and efficacy in this setting.
Nesr G, Laffan M, Claudiani S, et al., 2020, Platelet function in patients with chronic myeloid leukemia treated with asciminib, Leukemia & Lymphoma, Vol: 61, Pages: 3021-3023, ISSN: 1042-8194
Gupta RK, Peppa D, Hill AL, et al., 2020, Evidence for HIV-1 cure after <i>CCR5</i>Δ32/Δ32 allogeneic haemopoietic stem-cell transplantation 30 months post analytical treatment interruption: a case report, LANCET HIV, Vol: 7, Pages: E340-E347, ISSN: 2352-3018
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- Citations: 102
Ghani R, Mullish BH, McDonald JA, et al., 2020, 1144 FECAL MICROBIOTA TRANSPLANT FOR MULTI-DRUG RESISTANT ORGANISMS: IMPROVED CLINICAL OUTCOMES BEYOND INTESTINAL DECOLONISATION, Publisher: Elsevier BV, ISSN: 0016-5085
Sookramanien S, Szydlo R, Palanicawandar R, et al., 2020, Platelet recovery after the first cycle of DA chemotherapy for AML is an independent predictor of survival, 60th Annual Scientific Meeting of the British-Society-for-Haematology (BSH), Publisher: WILEY, Pages: 185-186, ISSN: 0007-1048
Banerjee R, Killeen N, Toma S, et al., 2020, Reduced Intensity Conditioning with Thiotepa-Fludarabine-Busulphan (TBF) and Post-Transplant Cyclophosphamide (PTC) Results in Rapid Complete Donor T-cell Chimerism in Haploidentical Recipients with Acute Myeloid Leukaemia, 60th Annual Scientific Meeting of the British-Society-for-Haematology (BSH), Publisher: WILEY, Pages: 180-181, ISSN: 0007-1048
Ghani R, Mullish BH, McDonald J, et al., 2020, Disease prevention not decolonisation: a cohort study for faecal microbiota transplantation for patients colonised with multidrug-resistant organisms, ECCMID 2020
Guerrero A, Herranz N, Sun B, et al., 2019, Cardiac glycosides are broad-spectrum senolytics, Nature Metabolism, Vol: 1, Pages: 1074-1088, ISSN: 2522-5812
Senescence is a cellular stress response that results in the stable arrest of old, damaged or pre-neoplastic cells. Oncogene-induced senescence is tumour suppressive but can also exacerbate tumorigenesis through the secretion of proinflammatory factors from senescent cells. Drugs that selectively kill senescent cells, termed ‘senolytics’, have proved beneficial in animal models of many age-associated diseases. In the present study, we show that the cardiac glycoside ouabain is a senolytic agent with broad activity. Senescent cells are sensitized to ouabain-induced apoptosis, a process mediated in part by induction of the proapoptotic Bcl-2 family protein NOXA. We demonstrate that cardiac glycosides synergize with anti-cancer drugs to kill tumour cells and eliminate senescent cells that accumulate after irradiation or in old mice. Ouabain also eliminates senescent pre-neoplastic cells. The findings of the present study suggest that cardiac glycosides may be effective anti-cancer drugs by acting through multiple mechanisms. Given the broad range of senescent cells targeted by cardiac glycosides, their use against age-related diseases warrants further exploration.
Cuartero S, Innes AJ, Merkenschlager M, 2019, Towards a better understanding of cohesin mutations in AML, Frontiers in Oncology, Vol: 9, ISSN: 2234-943X
Classical driver mutations in acute myeloid leukemia (AML) typically affect regulatorsof cell proliferation, differentiation, and survival. The selective advantage of increasedproliferation, improved survival, and reduced differentiation on leukemia progression isimmediately obvious. Recent large-scale sequencing efforts have uncovered numerousnovel AML-associated mutations. Interestingly, a substantial fraction of the mostfrequently mutated genes encode general regulators of transcription and chromatinstate. Understanding the selective advantage conferred by these mutations remains amajor challenge. A striking example are mutations in genes of the cohesin complex,a major regulator of three-dimensional genome organization. Several landmark studieshave shown that cohesin mutations perturb the balance between self-renewal anddifferentiation of hematopoietic stem and progenitor cells (HSPC). Emerging data nowbegin to uncover the molecular mechanisms that underpin this phenotype. Amongthese mechanisms is a role for cohesin in the control of inflammatory responses inHSPCs and myeloid cells. Inflammatory signals limit HSPC self-renewal and driveHSPC differentiation. Consistent with this, cohesin mutations promote resistance toinflammatory signals, and may provide a selective advantage for AML progression.In this review, we discuss recent progress in understanding cohesin mutations inAML, and speculate whether vulnerabilities associated with these mutations could beexploited therapeutically
Innes A, Wooley P, Szydlo R, et al., 2019, Complete remission with incomplete count recovery (CRi) prior to allogeneic HCT for acute myeloid leukaemia is associated with a high non-relapse mortality., Leukemia, Vol: 34, Pages: 667-670, ISSN: 1476-5551
Beckerson J, Szydlo RM, Hickson M, et al., 2019, Impact of route and adequacy of nutritional intake on outcomes of allogeneic haematopoietic cell transplantation for haematologic malignancies, Clinical Nutrition, Vol: 38, Pages: 738-744, ISSN: 0261-5614
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 < .001. There were increased incidences of gastrointestinal GvHD of any stage and all GvHD ≥ grade 2 in patients who received PN (odds ratio (OR) 2.0; 95% CI 1.2-3.3; P = .006, and OR 1.8; 95% CI 1.1-3.0; P = .018, respectively), compared to adequate EN. Patients who received adequate PN and inadequate nutrition also had reduced probabilities of survival and GRFS at 5 years. CONCLUSION: Adequate EN during the early transplantation course is associated with reduced NRM, improved survival and GRFS at 5 years. Furthermore, adequate EN is associated with lower incidence of overall and gut acute GvHD than PN, perhaps because of its ability to maintain mucosal integrity, modulate the immune response to intensive chemo/radiotherapy and support the gastroi
Gupta RK, Abdul-Jawad S, McCoy LE, et al., 2019, HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation, Nature, Vol: 568, Pages: 244-248, ISSN: 0028-0836
A cure for HIV-1 remains unattainable as only one case has been reported, a decade ago1,2. The individual-who is known as the 'Berlin patient'-underwent two allogeneic haematopoietic stem-cell transplantation (HSCT) procedures using a donor with a homozygous mutation in the HIV coreceptor CCR5 (CCR5Δ32/Δ32) to treat his acute myeloid leukaemia. Total body irradiation was given with each HSCT. Notably, it is unclear which treatment or patient parameters contributed to this case of long-term HIV remission. Here we show that HIV-1 remission may be possible with a less aggressive and toxic approach. An adult infected with HIV-1 underwent allogeneic HSCT for Hodgkin's lymphoma using cells from a CCR5Δ32/Δ32 donor. He experienced mild gut graft-versus-host disease. Antiretroviral therapy was interrupted 16 months after transplantation. HIV-1 remission has been maintained over a further 18 months. Plasma HIV-1 RNA has been undetectable at less than one copy per millilitre along with undetectable HIV-1 DNA in peripheral CD4 T lymphocytes. Quantitative viral outgrowth assays from peripheral CD4 T lymphocytes show no reactivatable virus using a total of 24 million resting CD4 T cells. CCR5-tropic, but not CXCR4-tropic, viruses were identified in HIV-1 DNA from CD4 T cells of the patient before the transplant. CD4 T cells isolated from peripheral blood after transplantation did not express CCR5 and were susceptible only to CXCR4-tropic virus ex vivo. HIV-1 Gag-specific CD4 and CD8 T cell responses were lost after transplantation, whereas cytomegalovirus-specific responses were detectable. Similarly, HIV-1-specific antibodies and avidities fell to levels comparable to those in the Berlin patient following transplantation. Although at 18 months after the interruption of treatment it is premature to conclude that this patient has been cured, these data suggest that a single allogeneic HSCT with homozygous CCR5Δ32 donor cells may b
Innes A, Woolley P, Szydlo R, et al., 2019, Complete Remission with Incomplete Count Recovery (CRi) Prior to Allogeneic Haematopoietic Cell Transplantation for Acute Myeloid Leukaemia is Associated with a High Non-relapse Mortality without Increased Relapse Risk, 59th Annual Scientific Meeting of the British-Society-for-Hematology, Publisher: WILEY, Pages: 152-152, ISSN: 0007-1048
Innes AJ, Gil J, 2019, IMR90 ER:RAS: A cell model of oncogene-induced senescence, Methods in Molecular Biology, Vol: 1896, Pages: 83-92, ISSN: 1940-6029
Oncogene-induced senescence (OIS) is a cellular response that limits the replication of cells expressing oncogenes. As a result, OIS is a potent tumor suppressor mechanism limiting cancer progression. Here we describe IMR90 ER:RAS, a widely used model to study OIS in cell culture. This model takes advantage of IMR90 human primary fibroblast infected with a 4-hydroxy-tamoxifen (4-OHT) inducible ER:RAS construct. RAS activation upon 4-OHT treatment results in a coordinated induction of senescence, recapitulating different aspects of the phenotype such as the growth arrest and the establishment of a senescence-associated secretory phenotype (SASP).
Innes AJ, Woolley P, Szydlo R, et al., 2018, Complete remission with incomplete count recovery (CRi) prior to allogeneic hematopoietic cell transplantation for acute myeloid leukemia is associated with a high non-relapse mortality without increased relapse risk, 60th Annual Meeting of the American-Society-of-Hematology (ASH), Publisher: American Society of Hematology, ISSN: 1528-0020
González-Meljem JM, Hasting S, Gallage S, et al., 2018, Biomedical research in aging., Aging Research - Methodological Issues, Editors: García-Peña, Gutiérrez-Robledo, Pérez-Zepeda, Publisher: Springer, Pages: 25-54, ISBN: 9783319953861
Biomedical research has been instrumental in identifying key molecular and cellular changes that occur throughout the aging process, also known as the Hallmarks of Aging. Notably, these are shared between humans and several other species that have served as models for the study of aging in the laboratory. In this chapter, we discuss current knowledge regarding the significance of hallmarks such as: decay of stem cell function, acquisition of genomic instability, DNA damage, telomere attrition, deregulated nutrient sensing, chronic inflammation and cellular senescence. We further describe current methodological issues, experimental techniques and best practices for the study of each hallmark across different in vivo and in vitro systems, while also pointing at their limitations. Finally, we provide future perspectives for the improvement of experimental designs in biomedical research of aging.
Innes AJ, Matthey F, 2017, Red cell fragments can mask severe thrombocytopenia, BLOOD, Vol: 130, Pages: 1484-1484, ISSN: 0006-4971
Innes AJ, Mullish BH, Fernando F, et al., 2017, Faecal microbiota transplant: a novel biological approach to extensively drug-resistant organism-related non-relapse mortality., Bone Marrow Transplantation, Vol: 52, Pages: 1452-1454, ISSN: 1476-5365
Monsalvo S, Gabriel I, Sevillano B, et al., 2017, Exacerbation of multiple sclerosis symptoms in patients undergoing autologous stem cell transplantation, 43rd Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), Publisher: NATURE PUBLISHING GROUP, Pages: S419-S420, ISSN: 0268-3369
Pello OM, Bradshaw A, Innes A, et al., 2017, Clinical efficacy of BK virus specific T-cells in treatment of severe refractory hemorrhagic cystitis after HLA haploidentical transplantation, 43rd Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), Publisher: NATURE PUBLISHING GROUP, Pages: S483-S484, ISSN: 0268-3369
Innes AJ, Lee M, Francis N, et al., 2017, Immunosuppression-associated Kaposi sarcoma following stem cell transplantation, BRITISH JOURNAL OF HAEMATOLOGY, Vol: 178, Pages: 9-9, ISSN: 0007-1048
Khoder A, Sever M, Palanicawandar R, et al., 2017, PLERIXAFOR EFFECTIVELY RESCUES BIOSIMILAR G-CSFALONE-BASED STEM CELL MOBILISATION FAILURES, Publisher: ELSEVIER SCI LTD, Pages: S55-S55, ISSN: 1465-3249
Chapman MS, Innes A, Milojkovic, et al., 2017, A retrospective analysis of patients testing positive for the JAK2 V617F mutation: correlation between mutant allele burden and disease phenotype, 57th Annual Scientific Meeting of the British Society for Haematology, ISSN: 0007-1048
Pello OM, Innes AJ, Bradshaw A, et al., 2017, BKV-specific T cells in the treatment of severe refractory haemorrhagic cystitis after HLA-haploidentical haematopoietic cell transplantation, EUROPEAN JOURNAL OF HAEMATOLOGY, Vol: 98, Pages: 632-634, ISSN: 0902-4441
Background:Haemorrhagic cystitis caused by BK virus (BKV) is a known complication of allogeneic haematopoietic cell transplantation (HCT) and is relatively common following HLA-haploidentical transplantation. Adoptive immunotransfer of virus-specific T cells from the donor is a promising therapeutic approach, although production of these cells is challenging, particularly when dealing with low-frequency T cells such as BKV-specific T cells.Case report:Here, we present a patient who, following haploidentical HCT, developed severe BKV haemorrhagic cystitis, resistant to standard therapy. He responded well to adoptive transfer of donor cells enriched in BKV-specific T cells using the new second-generation CliniMACS Prodigy and the Cytokine Capture System from Miltenyi Biotec. Treatment led to full resolution of both the symptoms and viraemia without unwanted complications.Conclusion:Our observations suggest that use of products enriched with BKV-specific T cells generated using this system is safe and efficient in HLA-haploidentical HCT where BKV cystitis can be a serious complication.
Patel A, Szydlo RM, Auner HW, et al., 2016, C-reactive protein prior to myeloablative allogeneic haematopoietic cell transplantation identifies patients at risk of early- and long-term mortality, British Journal of Haematology, Vol: 180, Pages: 889-892, ISSN: 1365-2141
Wong CL, Innes AJ, Ma B, et al., 2016, Differential Expression of Genes Associated with Oncogene-Induced Senescence and Senescence Associated Secretory Phenotype in the Absence of Differential Expression of High Molecular Risk Genes and Genes Associated with JAK-STAT Pathway in Sorted Cells of Patients with Polycythemia Vera and Primary Myelofibrosis, 59th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH)/Symposium on the Basic Science of Hemostasis and Thrombosis, Publisher: American Society of Hematology, Pages: 4283-4283, ISSN: 0006-4971
Monsalvo S, Sevillano B, Innes AJ, et al., 2016, The Intensive Care Trial for Critically Ill Onco-Haematologic Patients: The Need for Response Criteria at 5 Days of Full Treatment to Separate Good Risk Patients and Avoid Futile Intensive Care Interventions, 59th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH)/Symposium on the Basic Science of Hemostasis and Thrombosis, Publisher: American Society of Hematology, Pages: 5987-5987, ISSN: 0006-4971
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