Dataset Information

NOD2 Polymorphisms and Their Impact on Haematopoietic Stem Cell Transplant Outcome.

ABSTRACT: Haematopoietic stem cell transplantation (HSCT) is a valuable tool in the treatment of many haematological disorders. Advances in understanding HLA matching have improved prognoses. However, many recipients of well-matched HSCT develop posttransplant complications, and survival is far from absolute. The pursuit of novel genetic factors that may impact on HSCT outcome has resulted in the publication of many articles on a multitude of genes. Three NOD2 polymorphisms, identified as disease-associated variants in Crohn's disease, have recently been suggested as important candidate gene markers in the outcome of HSCT. It was originally postulated that as the clinical manifestation of inflammatory responses characteristic of several post-transplant complications was of notable similarity to those seen in Crohn's disease, it was possible that they shared a common cause. Since the publication of this first paper, numerous studies have attempted to replicate the results in different transplant settings. The data has varied considerably between studies, and as yet no consensus on the impact of NOD2 SNPs on HSCT outcome has been achieved. Here, we will review the existing literature, summarise current theories as to why the data differs, and suggest possible mechanisms by which the SNPs affect HSCT outcome.

SUBMITTER: Mayor NP

PROVIDER: S-EPMC3483648 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

NOD2 Polymorphisms and Their Impact on Haematopoietic Stem Cell Transplant Outcome.

Mayor Neema P NP Shaw Bronwen E BE Madrigal J Alejandro JA Marsh Steven G E SG

Bone marrow research 20121018

Haematopoietic stem cell transplantation (HSCT) is a valuable tool in the treatment of many haematological disorders. Advances in understanding HLA matching have improved prognoses. However, many recipients of well-matched HSCT develop posttransplant complications, and survival is far from absolute. The pursuit of novel genetic factors that may impact on HSCT outcome has resulted in the publication of many articles on a multitude of genes. Three NOD2 polymorphisms, identified as disease-associat ...[more]

PMID: 23119165

Similar Datasets

Project description:IntroductionPatients receiving a haematopoietic stem cell transplant (HSCT) are subjected to complex oral medications based on prophylactic and immunosuppressive treatments. Adherence to medication plays a role in survival, and medication non-adherence (MNA) is closely associated with graft-versus-host disease and other complications. The aim of this systematic review is to summarise the available evidence regarding prevalence rates of medication adherence, the risk factors of MNA, the effectiveness of interventions to increase medication adherence and the outcomes associated with MNA.Methods and analysisWe designed a systematic review according to the Joanna Briggs Institute methodology. We will search the Cochrane Library and the CINAHL, EMBASE, MEDLINE via PubMed, PsycINFO and Scopus databases. We will include published and unpublished primary studies: (a) on humans, from inception until 10 May 2022; (b) written in any language; (c) experimental (randomised and non-randomised), observational (prospective, retrospective cohort and case-control), correlational, cross-sectional and longitudinal; and (d) with a low risk of bias, according to the quality assessment we perform. We will exclude secondary and qualitative studies, protocols, publications without original data, including paediatrics or related to autologous HSCT. The primary outcome will be the prevalence of oral medication adherence; the secondary outcomes will be the risk factors of MNA, the interventions aimed at increasing medication adherence and the outcomes of MNA. Two researchers will independently screen the eligible studies, then extract and describe the data. Disagreements will be resolved by a third researcher. We will provide a qualitative narrative synthesis of the findings.Ethics and disseminationEthical approval is not required given that previously published studies will be used. We will disseminate the findings through conference presentations and publications in international peer-reviewed scientific journals.Prospero registration numberCRD42022315298.

Project description:BackgroundThe role of conditioning intensity and stem cell source on modifying pre-transplantation risk in allogeneic haematopoietic stem cell transplantation (HSCT) is a matter of debate, but crucial when benchmarking centres.MethodsThis Retrospective, multicenter exploratory-validation analysis of 9103 patients, (55.5% male, median age 50 years; 1-75 years range) with an allogeneic HSCT between 2010 and 2016 from a matched sibling (N = 8641; 95%) or matched unrelated donor (N = 462; 5%) for acute myeloid (N = 6432; 71%) or acute lymphoblastic (N = 2671; 29%) leukaemia in first complete remission, and reported by 240 centres in 30 countries to the benchmark database of the European Society for Blood and Marrow Transplantation (EBMT) searched for factors associated with use of transplant techniques (standard N = 6375;70% or reduced intensity conditioning N = 2728;30%, respectively bone marrow N = 1945;21% or peripheral blood N = 7158;79% as stem cell source), and their impact on outcome.FindingsTreatment groups differed significantly from baseline population (p < 0.001), and within groups regarding patient-, disease-, donor-, and centre-related pre-transplantation risk factors (p < 0.001); choice of technique did depend on pre-transplantation risk factors and centre (p < 0.001). Probability of overall survival at 5 years decreased systematically and significantly with increasing pre-transplantation risk score (score 2 vs 0/1 HR: 1·2, 95% c.i. [1·1-1·.3], p = 0.002; score 3 vs 0/1 HR: 1·5, 95% c.i. [1·3-1·7], p < 0.001; score 4/5/6 vs 0/1 HR: 1·9, 95% c.i. [1·6-2·2], p < 0.001) with no significant differences between treatment groups (likelihood ratio test on interaction: p = 0.40). Overall survival was significantly associated with selection steps and completeness of information (p < 0.001).InterpretationPatients' pre-transplantation risk factors determine survival, independent of transplant techniques. Transplant techniques should be regarded as centre policy, not stratification factor in benchmarking. Selection criteria and completeness of data bias outcome. Outcomes may be improved more effectively through better identifying pre-transplantation factors as opposed to refinement of transplant techniques.FundingThe study was funded by EBMT.

Project description:AimsBusulfan and treosulfan are cytotoxic agents used in the conditioning regime prior to paediatric haematopoietic stem cell transplantation (HSCT). These agents cause suppression of myeloid cells leaving patients severely immunocompromised in the early post-HSCT period. The main objectives were: (i) to establish a mechanistic pharmacokinetic-pharmacodynamic (PKPD) model for the treatment and engraftment effects on neutrophil counts comparing busulfan and treosulfan-based conditioning, and (ii) to explore current dosing schedules with respect to time to HSCT.MethodsData on 126 patients, 72 receiving busulfan (7 months-18 years, 5.1-47.0 kg) and 54 treosulfan (4 months-17 years, 3.8-35.8 kg), were collected. In total, 8935 neutrophil count observations were recorded during the study period in addition to drug concentrations to develop a mechanistic PKPD model. Absolute neutrophil count profiles were modelled semimechanistically, accounting for transplant effects and differing set points pre- and post-transplant.ResultsPK were best described by 2-compartment models for both drugs. The Friberg semimechanistic neutropenia model was applied with a linear model for busulfan and a maximum efficacy model for treosulfan describing drug effects at various stages of neutrophil maturation. System parameters were consistent across both drugs. The HSCT was represented by an amount of progenitor cells enhancing the neutrophils' proliferation and maturation compartments. Alemtuzumab was found to enhance the proliferative rate under which the absolute neutrophil count begin to grow after HSCT.ConclusionA semimechanistic PKPD model linking exposure to either busulfan or treosulfan to the neutrophil reconstitution dynamics was successfully built. Alemtuzumab coadministration enhanced the neutrophil proliferative rate after HSCT. Treosulfan administration was suggested to be delayed with respect to time to HSCT, leaving less time between the end of the administration and stem cell infusion.

Dataset Information

NOD2 Polymorphisms and Their Impact on Haematopoietic Stem Cell Transplant Outcome.

Publications

NOD2 Polymorphisms and Their Impact on Haematopoietic Stem Cell Transplant Outcome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets