137 results found
Craddock C, Jackson A, Loke J, et al., 2020, Augmented Reduced-Intensity Regimen Does Not Improve Postallogeneic Transplant Outcomes in Acute Myeloid Leukemia., J Clin Oncol
PURPOSE: Reduced-intensity conditioning (RIC) regimens have extended the curative potential of allogeneic stem-cell transplantation to older adults with high-risk acute myeloid leukemia (AML) and myelodysplasia (MDS) but are associated with a high risk of disease relapse. Strategies to reduce recurrence are urgently required. Registry data have demonstrated improved outcomes using a sequential transplant regimen, fludarabine/amsacrine/cytarabine-busulphan (FLAMSA-Bu), but the impact of this intensified conditioning regimen has not been studied in randomized trials. PATIENTS AND METHODS: Two hundred forty-four patients (median age, 59 years) with high-risk AML (n = 164) or MDS (n = 80) were randomly assigned 1:1 to a fludarabine-based RIC regimen or FLAMSA-Bu. Pretransplant measurable residual disease (MRD) was monitored by flow cytometry (MFC-MRD) and correlated with outcome. RESULTS: There was no difference in 2-year overall survival (hazard ratio 1.05 [85% CI, 0.80 to 1.38] P = .81) or cumulative incidence of relapse (CIR) (hazard ratio 0.94 [95%CI, 0.60 to 1.46] P = .81) between the control and FLAMSA-Bu arms. Detectable pretransplant MFC-MRD was associated with an increased CIR (2-year CIR 41.0% v 20.0%, P = .01) in the overall trial cohort with a comparable prognostic impact when measured by an unsupervised analysis approach. There was no evidence of interaction between MRD status and conditioning regimen intensity for relapse or survival. Acquisition of full donor T-cell chimerism at 3 months abrogated the adverse impact of pretransplant MRD on CIR and overall survival. CONCLUSION: The intensified RIC conditioning regimen, FLAMSA-Bu, did not improve outcomes in adults transplanted for high-risk AML or MDS regardless of pretransplant MRD status. Our data instead support the exploration of interventions with the ability to accelerate acquisition of full donor T-cell chimerism as a tractable strategy to improve outcomes in patients allografted for AML.
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
Ghani R, Mullish BH, McDonald JAK, et al., 2020, Disease prevention not decolonization – a model for fecal microbiota transplantation in patients colonized with multidrug-resistant organisms, Clinical Infectious Diseases, ISSN: 1058-4838
Fecal microbiota transplantation (FMT) yields variable intestinal decolonization results for multidrug-resistant organisms (MDROs). This study showed significant reductions in antibiotic duration, bacteremia and length of stay in 20 patients colonized/ infected with MDRO receiving FMT (compared to pre-FMT history, and a matched group not receiving FMT), despite modest decolonization rates.
Penack O, Peczynski C, van der Werf S, et al., 2020, Association of uric acid levels before start of conditioning with mortality after allogeneic hematopoietic stem cell transplantation - a prospective, non-interventional study of the EBMT Transplant Complication Working Party, 45th Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), Publisher: FERRATA STORTI FOUNDATION, Pages: 1977-1983, ISSN: 0390-6078
Nagler A, Dholaria B, Labopin M, et al., 2020, Bone marrow versus mobilized peripheral blood stem cell graft in T-cell-replete haploidentical transplantation in acute lymphoblastic leukemia, LEUKEMIA, Vol: 34, Pages: 2766-2775, ISSN: 0887-6924
Ghani R, Mullish BH, McDonald JA, et al., 2020, 1144 FECAL MICROBIOTA TRANSPLANT FOR MULTI-DRUG RESISTANT ORGANISMS: IMPROVED CLINICAL OUTCOMES BEYOND INTESTINAL DECOLONISATION, Gastroenterology, Vol: 158, ISSN: 0016-5085
Penack O, Peczynski C, van der Werf S, et al., 2020, Association of Serum Ferritin Levels Before Start of Conditioning With Mortality After alloSCT - A Prospective, Non-interventional Study of the EBMT Transplant Complications Working Party, FRONTIERS IN IMMUNOLOGY, Vol: 11, ISSN: 1664-3224
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
Salooja N, Ghani L, Stuart J, et al., 2020, Morbidity of very long term (> 30 year) survivors of allogeneic haemopoietic cell transplantation 1979-1989: a single centre experience, 60th Annual Scientific Meeting of the British-Society-for-Haematology (BSH), Publisher: WILEY, Pages: 181-182, ISSN: 0007-1048
Craddock C, Jackson A, Malladi R, et al., 2020, The FLAMSA-Bu conditioning regimen does not improve outcome in patients allografted for high-risk acute myeloid leukaemia and myelodysplasia irrespective of pretransplant MRD: results of the UK NCRI FIGARO trial, 60th Annual Scientific Meeting of the British-Society-for-Haematology (BSH), Publisher: WILEY, Pages: 5-5, 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
Anthias C, Apperley J, Bloor A, et al., 2020, Reducing the diversity of allogeneic transplant protocols in the UK through a BSBMT Anthony Nolan Protocol Harmonization Initiative, BONE MARROW TRANSPLANTATION, Vol: 55, Pages: 1840-1843, ISSN: 0268-3369
Rio-Machin A, Vulliamy T, Hug N, et al., 2020, The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants, Nature Communications, Vol: 11, Pages: 1-12, ISSN: 2041-1723
The inclusion of familial myeloid malignancies as a separate disease entity in the revised WHO classification has renewed efforts to improve the recognition and management of this group of at risk individuals. Here we report a cohort of 86 acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) families with 49 harboring germline variants in 16 previously defined loci (57%). Whole exome sequencing in a further 37 uncharacterized families (43%) allowed us to rationalize 65 new candidate loci, including genes mutated in rare hematological syndromes (ADA, GP6, IL17RA, PRF1 and SEC23B), reported in prior MDS/AML or inherited bone marrow failure series (DNAH9, NAPRT1 and SH2B3) or variants at novel loci (DHX34) that appear specific to inherited forms of myeloid malignancies. Altogether, our series of MDS/AML families offer novel insights into the etiology of myeloid malignancies and provide a framework to prioritize variants for inclusion into routine diagnostics and patient management.
Ellington MJ, Davies F, Jauneikaite E, et al., 2019, A multi-species cluster of GES-5 carbapenemase producing Enterobacterales linked by a geographically disseminated plasmid, Clinical Infectious Diseases, 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.
Nagler A, Labopin M, Angelucci E, et al., 2019, Bone Marrow Versus Mobilized Peripheral Blood Stem Cells for Non T Depleted Haploidentical Transplantations with Post Transplantation Cyclophosphamide in Acute Lymphoblastic Leukemia: On Behalf of the ALWP of the EBMT, 61st Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Craddock C, Jackson AE, Malladi RK, et al., 2019, The Sequential Flamsa-Bu Conditioning Regimen Does Not Improve Outcome in Patients Allografted for High Risk Acute Myeloid and Myelodysplasia Irrespective of Pre-Transplant MRD Status: Results of the UK NCRI Figaro Trial, 61st Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Pavlu J, Labopin M, Niittyvuopio R, et al., 2019, Measurable residual disease at myeloablative allogeneic transplantation in adults with acute lymphoblastic leukemia: a retrospective registry study on 2780 patients from the acute leukemia working party of the EBMT, Journal of Hematology and Oncology, Vol: 12, Pages: 1-9, ISSN: 1756-8722
BackgroundAssessment of measurable residual disease (MRD) is rapidly transforming the therapeutic and prognostic landscape of a wide range of hematological malignancies. Its prognostic value in acute lymphoblastic leukemia (ALL) has been established and MRD measured at the end of induction is increasingly used to guide further therapy. Although MRD detectable immediately before allogeneic hematopoietic cell transplantation (HCT) is known to be associated with poor outcomes, it is unclear if or to what extent this differs with different types of conditioning.MethodsIn this retrospective registry study, we explored whether measurable residual disease (MRD) before allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia is associated with different outcomes in recipients of myeloablative total body irradiation (TBI)-based versus chemotherapy-based conditioning. We analyzed outcomes of 2780 patients (median age 38 years, range 18–72) who underwent first HCT in complete remission between 2000 and 2017 using sibling or unrelated donors.ResultsIn 1816 of patients, no disease was detectable, and in 964 patients, MRD was positive. Conditioning was TBI-based in 2122 (76%) transplants. In the whole cohort MRD positivity was a significant independent factor for lower overall survival (OS) and leukemia-free survival (LFS), and for higher relapse incidence (RI), with respective hazard ratios (HR, 95% confidence intervals) of 1.19 (1.02–1.39), 1.26 (1.1–1.44), and 1.51 (1.26–1.8). TBI was associated with a higher OS, LFS, and lower RI with HR of 0.75 (0.62–0.90), 0.70 (0.60–0.82), and 0.60 (0.49–0.74), respectively. No significant interaction was found between MRD status and conditioning. When investigating the impact of MRD separately in the TBI and chemotherapy-based conditioning cohorts by multivariate analysis, we found MRD positivity to be associated with lower OS and LFS and higher RI in the TBI gro
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
Bassan R, Hoelzer D, Thomas X, et al., 2019, Clinician Concepts of Cure in Adult Relapsed and Refractory Philadelphia-Negative B Cell Precursor Acute Lymphoblastic Leukemia: A Delphi Study, ADVANCES IN THERAPY, Vol: 36, Pages: 870-879, ISSN: 0741-238X
Aldiwani M, Tharakan T, Al-Hassani A, et al., 2019, BK Virus Associated Haemorrhagic Cystitis. A systematic review of current prevention and treatment strategies, INTERNATIONAL JOURNAL OF SURGERY, Vol: 63, Pages: 34-42, ISSN: 1743-9191
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
Pavlu J, Labopin M, Niittyvuopio R, et al., 2019, The Role of Measurable Residual Disease (MRD) at Time of Allogeneic Hematopoietic Cell Transplantation in Adults with Acute Lymphoblastic Leukemia Transplanted after Myeloablative Conditioning. A Study on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, Publisher: ELSEVIER SCIENCE INC, ISSN: 1083-8791
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
Snober M, Syzdlo R, Apperley J, et al., 2018, Incidence and Risk Factors for Second Malignancies after Transplant in Long Term Survivors of Allogeneic Haematopoietic Stem Cell Transplant: A Single Centre Experience, 60th Annual Meeting of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Woolley P, Slade D, Syzdlo R, et al., 2018, 34-Year Single Center Observational Review of Ex-Vivo T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplants for Chronic Myeloid Leukemia, 60th Annual Meeting of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Ghani R, Mookerjee S, Mullish BH, et al., 2018, Impact on Length of Stay and Antibiotic Use in Allogenic and Autologous Stem Cell Transplant Patients Colonized with Carbapenemase-producing Enterobacteriaceae, IDWeek, Publisher: Oxford University Press, ISSN: 2328-8957
Lozano S, Pello O, Loaiza S, et al., 2018, Viral-specific T cell infusions for refractory viral infections after allogeneic stem cell transplantation, 44th Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), Publisher: NATURE PUBLISHING GROUP, Pages: 387-388, ISSN: 0268-3369
Ainley L, Pavlu J, 2018, Ambulatory autologous stem cell transplantation for multiple myeloma and lymphoma: A single centre experience, 58th Annual Scientific Meeting of the British-Society-for-Haematology, Publisher: WILEY, Pages: 156-156, ISSN: 0007-1048
Craddock C, Tholouli E, Vicente SM, et al., 2017, Safety and Clinical Activity of Combined Romidepsin and Azacitidine Therapy in High Risk Acute Myeloid Leukemia: Preliminary Results of the Romaza Trial, 59th Annual Meeting of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
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