148 results found
Fernando F, Robertson HF, El-Zahab S, et al., 2021, How I Use Measurable Residual Disease in the Clinical Management of Adult Acute Lymphoblastic Leukemia., Clin Hematol Int, Vol: 3, Pages: 130-141
Over the last decade the use of measurable residual disease (MRD) diagnostics in adult acute lymphoblastic leukemia (ALL) has expanded from a limited number of study groups in Europe and the United States to a world-wide application. In this review, we summarize the advantages and drawbacks of the current available techniques used for MRD monitoring. Through the use of three representative case studies, we highlight the advances in the use of MRD in clinical decision-making in the management of ALL in adults. We acknowledge discrepancies in MRD monitoring and treatment between different countries, reflecting differing availability, accessibility and affordability.
Loke J, Metzner M, Boucher R, et al., 2021, Combination romidepsin and azacitidine therapy is well tolerated and clinically active in adults with high-risk acute myeloid leukaemia ineligible for intensive chemotherapy, BRITISH JOURNAL OF HAEMATOLOGY, Vol: 196, Pages: 368-373, ISSN: 0007-1048
Innes AJ, Mullish BH, Ghani R, et al., 2021, Fecal microbiota transplant mitigates adverse outcomes in patients colonized with multidrug-resistant organisms undergoing allogeneic hematopoietic cell transplantation, Frontiers in Cellular and Infection Microbiology, Vol: 11, Pages: 1-8, ISSN: 2235-2988
The gut microbiome can be adversely affected by chemotherapy and antibiotics prior to hematopoietic cell transplantation (HCT).This affects graft success and increases susceptibility to multidrug-resistant organism (MDRO) colonization and infection. Weperformed an initial retrospective analysis of our use of fecal microbiota transplantation (FMT) from healthy donors as therapy forMDRO-colonized patients with hematological malignancy. FMT was performed on eight MDRO-colonized patients pre-HCT (FMT-MDROgroup), and outcomes compared with 11 MDRO colonized HCT patients from the same period. At 12 months, survival wassignificantly higher in the FMT-MDRO group (70% versus 36% p = 0.044). Post-HCT, fewer FMT-MDRO patients required intensivecare (0% versus 46%, P = 0.045) or experienced fever (0.29 versus 0.11 days, P = 0.027). Intestinal MDRO decolonization occurred in25% of FMT-MDRO patients versus 11% non-FMT MDRO patients. Despite the significant difference and statistically comparablepatient/transplant characteristics, as the sample size was small, a matched-pair analysis to non-MDRO colonized control cohorts(2:1 matching) was performed. At 12 months, the MDRO group who did not have an FMT had significantly lower survival (36.4%versus 61.9% respectively, p=0.012), and higher non relapse mortality (NRM; 60.2% versus 16.7% respectively, p=0.009) than theirpaired non-colonized cohort. There was no difference in survival (70% versus 43.4%, p=0.14) or NRM (12.5% versus 31.2%respectively, p=0.24) between the FMT-MDRO group and their paired cohort. Negative outcomes, including mortality associatedwith MDRO colonization, may be ameliorated by pre-HCT FMT, despite lack of intestinal decolonization. Further work is needed toexplore the observed benefit.
Geva M, Pryce A, Shouval R, et al., 2021, High lactate dehydrogenase at time of admission for allogeneic hematopoietic transplantation associates to poor survival in acute myeloid leukemia and non-Hodgkin lymphoma, BONE MARROW TRANSPLANTATION, Vol: 56, Pages: 2690-2696, ISSN: 0268-3369
Ruggeri A, Galimard JE, Labopin M, et al., 2021, Comparison of Haploidentical Peripheral Blood Cell Transplantation Using Post-Transplant Cyclophosphamide With Double Cord Blood Transplantation in Adults With Acute Leukemia, Publisher: SPRINGERNATURE, Pages: 24-25, ISSN: 0268-3369
Mullish BH, Innes AJ, Ghani R, et al., 2021, FECAL MICROBIOTA TRANSPLANT PRIOR TO ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANT IN PATIENTS COLONIZED WITH MULTI-DRUG RESISTANT ORGANISMS IS ASSOCIATED WITH IMPROVED SURVIVAL, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S168-S169, ISSN: 0016-5085
Ghani R, Mullish BH, McDonald JAK, et al., 2021, Disease prevention not decolonization – a model for fecal microbiota transplantation in patients colonized with multidrug-resistant organisms, Clinical Infectious Diseases, Vol: 72, Pages: 1444-1447, 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.
Craddock C, Jackson A, Loke J, et al., 2021, Augmented Reduced-Intensity Regimen Does Not Improve Postallogeneic Transplant Outcomes in Acute Myeloid Leukemia, JOURNAL OF CLINICAL ONCOLOGY, Vol: 39, Pages: 768-+, ISSN: 0732-183X
Dholaria B, Labopin M, Angelucci E, et al., 2021, Improved Outcomes of Haploidentical Hematopoietic Cell Transplantation with Total Body Irradiation-Based Myeloablative Conditioning in Acute Lymphoblastic Leukemia, TRANSPLANTATION AND CELLULAR THERAPY, Vol: 27, ISSN: 2666-6375
Ghani R, Mullish B, Innes A, et al., 2021, Faecal microbiota transplant (FMT) prior to allogeneic haematopoietic cell transplantation (HCT) in patients colonised with multidrug-resistant organisms (MDRO) results in improved survival, ECCMID
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
Giebel S, Labopin M, Angelucci E, et al., 2020, Total Body Irradiation/Fludarabine Versus Thiotepa/ busulfan/fludarabine for Adults with Acute Lymphoblastic Leukemia Treated with Haploidentical HCT. A Study by Acute Leukemia Working Party of the EBMT, Publisher: SPRINGERNATURE, Pages: 65-65, 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.
Devillier R, Galimard J-E, Labopin M, et al., 2020, Reduced Intensity Vs. Non-Myeloablative Conditioning Regimens for Haploidentical Transplantation in Complete Remission Acute Myeloid Leukemia: A Study from the ALWP of the EBMT, Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
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, Publisher: Elsevier BV, 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
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
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
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
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.
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
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
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
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