scholarly journals 61: NOD2/CARD15 gene single nucleotide polymorphisms are associated with significant increases in mortality due to increases in disease relapse in recipients of an unrelated donor haematopoietic stem cell transplant for acute leukaemia

2007 ◽  
Vol 13 (2) ◽  
pp. 25
Author(s):  
N.P. Mayor ◽  
B.E. Shaw ◽  
D.A. Hughes ◽  
H. Maldonado-Torres ◽  
J.A. Madrigal ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Leukaemia ◽  
Stem Cell Transplant ◽  
Haematopoietic Stem Cell ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Nucleotide Polymorphisms ◽  
Disease Relapse ◽  
Single Nucleotide ◽  
Card15 Gene

Single Nucleotide Polymorphisms of the NOD2/CARD15 Gene Are Associated with Significant Increases in Disease Relapse and Mortality in Recipients of an Unrelated Donor Haematopoietic Stem Cell Transplant for Acute Leukaemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 498-498
Author(s):  
Neema P. Mayor ◽  
Bronwen E. Shaw ◽  
Derralynn A. Hughes ◽  
Hazael Maldonado-Torres ◽  
J. Alejandro Madrigal ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Leukaemia ◽  
Stem Cell Transplant ◽  
Haematopoietic Stem Cell ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Nucleotide Polymorphisms ◽  
Disease Relapse ◽  
Single Nucleotide ◽  
Card15 Gene

Abstract Single Nucleotide Polymorphisms (SNPs) of the Caspase Recruitment Domain (CARD) 15 gene, also known as the Nucleotide-binding Oligomerisation Domain (NOD) 2 gene, have recently been implicated in the onset and pathogenicity of malignant diseases as well as in several inflammatory disorders, particularly Crohn’s Disease and Blau syndrome. More specifically, NOD2/CARD15 polymorphisms have been implicated with a significant increase in Transplant Related Mortality (TRM) and on the incidence of clinically significant acute Graft versus Host Disease (aGvHD) post-Haematopoietic Stem Cell Transplant (HSCT). In order to establish the impact of these SNPs on Unrelated Donor (UD) HSCT, NOD2/CARD15 genotyping was performed on 196 patients diagnosed with Acute Leukaemia and their volunteer UD. Transplants occurred between 1996 and 2003 at one of 25 transplant centres in the UK. Diagnoses were Acute Lymphoblastic Leukaemia (98/196, 50%) and Acute Myeloid Leukaemia (98/196, 50%). Recipients and donors were a 10/10 HLA allele match, that is HLA-A, -B, -C, -DRB1, and -DQB1, in 64% of pairs. Of these, 16% were a 12/12 HLA match (i.e. they were also matched at an allele level for HLA-DPB1). Myeloablative conditioning regimens were used in 78% of transplants. T-cell depletion was included in 83% of conditioning protocols, the majority of which was achieved using in-vivo alemtuzumab. Peripheral blood stem cells were used as a graft in 19% of transplants, with the remaining 81% using bone marrow. Two forms of post-transplant immunosuppression predominated, Cyclosporine A in combination with Methotrexate in 47% of transplants and Cyclosporine A alone in 31% of transplants. Polymorphisms of the NOD2/CARD15 gene within an UD-HSCT pair resulted in a significant increase in disease relapse and mortality. The estimated two-year incidence of disease relapse was 70% in pairs with NOD2/CARD15 SNPs as compared to 43% in pairs with wild type genotype (Log rank, P=0.0003). This resulted in a significant increase in mortality. The estimated three-year overall survival for the cohort was 22% and 44% for pairs with and without NOD2/CARD15 polymorphism respectively (Log rank, P=0.0087). These findings persisted in multivariate analysis. NOD2/CARD15 genotype was found to be the most significant factor for an adverse outcome other than being transplanted in a disease stage of relapse. We conclude that in contrast to previous findings, the presence of a NOD2/CARD15 SNP in the genotype of an Acute Leukaemia UD-HSCT pair results in a significant increase in disease relapse and subsequently a decrease in overall survival. These novel data show an important role for NOD2/CARD15 genotyping in transplantation and suggest a possible effect of the NOD2 protein in alloreactivity and tumour surveillance. Genotyping recipients and donors prior to transplant may allow for prediction of transplant outcome, and thus present critical information for donor selection.

Carbapenem-resistant Klebsiella pneumoniae colonization and infection is associated with lower overall survival in a cohort of haematopoietic stem-cell transplantation patients: mechanism of resistance and virulence by whole-genome sequencing

2021 ◽  
Vol 70 (10) ◽  
Author(s):  
Hermes Ryoiti Higashino ◽  
Ana Paula Marchi ◽  
Roberta Cristina Ruedas Martins ◽  
Laina Bubach Carvalho ◽  
Lauro Vieira Perdigão Neto ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Klebsiella Pneumoniae ◽  
Genome Sequencing ◽  
Stem Cell Transplant ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Whole Genome ◽  
Carbapenem Resistant ◽  
Overall Mortality

Carbapenem-resistant Klebsiella pneumoniae (CRK) infections are a growing concern in immunocompromised patients. The aim of the present study was to evaluate the impact of CRK colonization and infection in overall mortality for haematopoietic stem-cell transplant (HSCT) patients. We also aimed to investigate resistance and virulence profiles of CRK isolates and assess their epidemiological and genetic relatedness. Patients in the HSCT unit were screened for colonization with CRK with weekly rectal swab or stool cultures and placed under contact precautions. We defined CRK colonization as positive culture from a swab or stool sample grown in MacConkey agar with meropenem at 1 µg ml−1. Demographic and clinical data were retrieved from the patients’ charts and electronic records. According to resistance mechanisms and pulsed field gel electrophoresis profile, isolates were selected based on whole-genome sequencing (WGS) using MiSeq Illumina. Outcomes were defined as overall mortality (death up to D+100), and infection-related death (within 14 days of infection). We report a retrospective cohort of 569 haematopoietic stem-cell transplant patients with 105 (18.4 %) CRK colonizations and 30 (5.3 %) infections. blaKPC was the most frequent carbapenemase in our cohort with three isolates co-harbouring blaKPC and blaNDM. We found no difference in virulence profiles from the CRK isolates. There were also no significant differences in virulence profiles among colonization and infection isolates regarding genes encoding for type 1 and 3 fimbriae, siderophores, lipopolysaccharide and colibactin. In clonality analysis by PFGE and WGS, isolates were polyclonal and ST340 was the most prevalent. Overall survival at D+100 was 75.4 % in in CRK-colonized (P=0.02) and 35.7 % in infected patients and significantly lower than non-colonized patients (85.8 %; P<0.001). We found a higher overall mortality associated with colonization and infection; KPC was the main resistance mechanism for carbapenems. The polyclonal distribution of isolates and findings of CRK infection in patients not previously colonized suggest the need to reinforce antibiotic stewardship.

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