123 results found
Rio-Machin A, Vulliamy T, Hug N, et al., 2020, The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants., Nat Commun, Vol: 11
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.
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
Penack O, Peczynski C, van der Werf S, et al., 2019, Association of uric acid levels before start of conditioning with mortality after alloSCT - 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: NATURE PUBLISHING GROUP, Pages: 296-297, ISSN: 0268-3369
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
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
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
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
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
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
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
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
Ghani L, Salooja N, Stuart J, et al., 2017, Microalbuminuria in long-term survivors of hematopoietic cell transplant: a retrospective single-centre study, 43rd Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), Publisher: NATURE PUBLISHING GROUP, Pages: S300-S300, ISSN: 0268-3369
Khoder A, Palanicawandar R, Atta M, et al., 2017, The choice between stem cell mobilisation with GCSF alone or with GCSF plus chemotherapy may impact on the stem cell transplant service, 43rd Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), Publisher: NATURE PUBLISHING GROUP, Pages: S146-S147, ISSN: 0268-3369
Monsalvo S, Sevillano B, Palanicawandar R, et al., 2017, Changes in intensive care for stem cell transplant patients: the need for response criteria at 5 days of full treatment to separate good risk patients and avoid futile interventions, 43rd Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), Publisher: NATURE PUBLISHING GROUP, Pages: S278-S278, 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
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
Sevillano B, Monsalvo S, Lozano S, et al., 2017, Ciclosporin toxicity: Increased mortality and incidence of chronic GvHD after stopping Ciclosporin A and replacing it with mycophenolate mofetil as prophylaxis for GvHD, 43rd Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), Publisher: NATURE PUBLISHING GROUP, Pages: S204-S205, ISSN: 0268-3369
Giebel S, Labopin M, Socie G, et al., 2017, CYCLOPHOSPHAMIDE VERSUS ETOPOSIDE IN COMBINATION WITH TOTAL BODY IRRADIATION AS CONDITIONING FOR ADULTS WITH PH(-) ALL UNDERGOING ALLO-HCT. A STUDY FROM THE ACUTE LEUKEMIA WORKING PARTY OF THE EBMT, 22nd Congress of the European-Hematology-Association, Publisher: FERRATA STORTI FOUNDATION, Pages: 326-326, ISSN: 0390-6078
Pavlu J, Auner H, Szydlo RM, et al., 2017, Analysis of hematopoietic recovery after autologous transplantation as method of quality control for long-term progenitor cell cryopreservation., Bone Marrow Transplantation, Vol: 52, Pages: 1599-1601, ISSN: 1476-5365
Hematopoietic precursor cells (HPC) are able to restore hematopoiesis after high-dose chemotherapy and their cryopreservation is routinely employed prior to the autologous hematopoietic cell transplantation (AHCT). Although previous studies showed feasibility of long-term HPC storage, concerns remain about possible negative effects on their potency. To study the effects of long-term cryopreservation, we compared time to neutrophil and platelet recovery in 50 patients receiving two AHCT for multiple myeloma at least 2 years apart between 2006 and 2016, using HPC obtained from one mobilization and collection attempt before the first transplant. This product was divided into equivalent fractions allowing a minimum of 2 × 106 CD34+ cells/kg recipient’s weight. One fraction was used for the first transplant after median storage of 60 days (range, 17–165) and another fraction was used after median storage of 1448 days (range, 849–3510) at the second AHCT. Neutrophil recovery occurred at 14 days (median; range, 11–21) after the first and 13 days (10–20) after the second AHCT. Platelets recovered at a median of 16 days after both procedures. Considering other factors, such as disease status, conditioning and HPC dose, this single institution data demonstrated no reduction in the potency of HPC after long-term storage.
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
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.
Pavlu J, Labopin M, Zoellner AK, et al., 2017, Allogeneic hematopoietic cell transplantation for primary refractory acute lymphoblastic leukemia: A report from the Acute Leukemia Working Party of the EBMT, Cancer, Vol: 123, Pages: 1965-1970, ISSN: 0008-543X
BACKGROUND: Patients with primary refractory acute lymphoblastic leukemia (PREF ALL) who fail to achieve a complete remission(CR) after 2 courses of chemotherapy have a dismal prognosis without undergoing allogeneic hematopoietic cell transplantation(HCT). To the authors’ knowledge, there currently are no data regarding factors influencing transplantation outcomes. METHODS: Theauthors retrospectively studied outcomes of transplantation for cases of PREF ALL reported to European Society for Blood andMarrow Transplantation registry. Eligibility criteria for the current analysis included adult patients who underwent their first HCT forPREF ALL between 2000 and 2012. PREF disease was defined as the failure to achieve a morphological CR after 2 courses of inductionchemotherapy. RESULTS: Data regarding 86 adult patients were analyzed. With a median follow-up of 106 months, the probabilityof survival was 36% at 2 years and 23% at 5 years. The probability of leukemia-free survival was 28% and 17%, respectively, and theprobability of nonrecurrence mortality was 20% and 29%, respectively, at 2 years and 5 years. For 66 patients who achieved a CR(77%), the survival at 2 years and 5 years was 36% and 29%, respectively. In multivariate analysis, use of total body irradiation wasfound to be associated with improved survival. Total body irradiation and infusion of female hematopoietic cells into male recipientswas associated with improved leukemia-free survival. These findings were incorporated into a scoring system that identified 3 groups(those with 2, 1, or no prognostic factors) with survival rates of 57%, 22%, and 8%, respectively. CONCLUSIONS: Although overall thesepatients would clearly benefit from the introduction of novel antileukemic therapies, the data from the current study support the useof allogeneic HCT in selected patients with PREF ALL.
Freeman S, Hodgkinson A, Nagra S, et al., 2017, Tracking MRD together with LSC Enriched Populations to Predict Transplant Outcomes in AML, ANNALS OF HEMATOLOGY, Vol: 96, Pages: S23-S24, ISSN: 0939-5555
Pavlu J, Labopin M, Tischer J, et al., 2016, Allogeneic Hematopoietic Stem Cell Transplantation for Primary Refractory Acute Lymphoblastic Leukemia - a Report from the Acute Leukemia Working Party of the EBMT, 58th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
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