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Low pre-transplant levels of mannose-binding lectin are associated with viral infections and mortality after haematopoietic allogeneic stem cell transplantation.

ABSTRACT: BACKGROUND:Mannose-binding lectin (MBL) is a key component of innate immunity. Low serum MBL levels, related to promoter polymorphism and structural variants, have been associated with an increased risk of infection. The aim of this work was to analyse the incidence and severity of infections and mortality in relation to the MBL2 genotype and MBL levels in patients underwent allogeneic haematopoietic stem cell transplantation (Allo-HSCT). RESULTS:This was a prospective cohort study of 72 consecutive patients underwent Allo-HSCT between January 2007 and June 2009 in a tertiary referral centre. Three periods were considered in the patients' follow-up: the early period (0-30?days after Allo-HSCT), the intermediate period (30-100?days after Allo-HSCT) and the late period (>?100?days after Allo-HSCT). A commercial line probe assay for MBL2 genotyping and an ELISA Kit were used to measure MBL levels. A total of 220 episodes of infection were collected in the 72 patients. No association between donor or recipient MBL2 genotype and infection was found. The first episode of infection presented earlier in patients with pre-transplant MBL levels of

SUBMITTER: Puente M

PROVIDER: S-EPMC6842494 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Low pre-transplant levels of mannose-binding lectin are associated with viral infections and mortality after haematopoietic allogeneic stem cell transplantation.

Puente M M Fariñas-Alvarez C C Moreto A A Sánchez-Velasco P P Ocejo-Vinyals J G JG Fariñas M C MC

BMC immunology 20191109 1

<h4>Background</h4>Mannose-binding lectin (MBL) is a key component of innate immunity. Low serum MBL levels, related to promoter polymorphism and structural variants, have been associated with an increased risk of infection. The aim of this work was to analyse the incidence and severity of infections and mortality in relation to the MBL2 genotype and MBL levels in patients underwent allogeneic haematopoietic stem cell transplantation (Allo-HSCT).<h4>Results</h4>This was a prospective cohort stud ...[more]

PMID: 31706269

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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:Haematopoietic stem cell transplantation has been proposed as treatment for mitochondrial neurogastrointestinal encephalomyopathy, a rare fatal autosomal recessive disease due to TYMP mutations that result in thymidine phosphorylase deficiency. We conducted a retrospective analysis of all known patients suffering from mitochondrial neurogastrointestinal encephalomyopathy who underwent allogeneic haematopoietic stem cell transplantation between 2005 and 2011. Twenty-four patients, 11 males and 13 females, median age 25 years (range 10-41 years) treated with haematopoietic stem cell transplantation from related (n = 9) or unrelated donors (n = 15) in 15 institutions worldwide were analysed for outcome and its associated factors. Overall, 9 of 24 patients (37.5%) were alive at last follow-up with a median follow-up of these surviving patients of 1430 days. Deaths were attributed to transplant in nine (including two after a second transplant due to graft failure), and to mitochondrial neurogastrointestinal encephalomyopathy in six patients. Thymidine phosphorylase activity rose from undetectable to normal levels (median 697 nmol/h/mg protein, range 262-1285) in all survivors. Seven patients (29%) who were engrafted and living more than 2 years after transplantation, showed improvement of body mass index, gastrointestinal manifestations, and peripheral neuropathy. Univariate statistical analysis demonstrated that survival was associated with two defined pre-transplant characteristics: human leukocyte antigen match (10/10 versus <10/10) and disease characteristics (liver disease, history of gastrointestinal pseudo-obstruction or both). Allogeneic haematopoietic stem cell transplantation can restore thymidine phosphorylase enzyme function in patients with mitochondrial neurogastrointestinal encephalomyopathy and improve clinical manifestations of mitochondrial neurogastrointestinal encephalomyopathy in the long term. Allogeneic haematopoietic stem cell transplantation should be considered for selected patients with an optimal donor.

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Low pre-transplant levels of mannose-binding lectin are associated with viral infections and mortality after haematopoietic allogeneic stem cell transplantation.

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Low pre-transplant levels of mannose-binding lectin are associated with viral infections and mortality after haematopoietic allogeneic stem cell transplantation.

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