The Impact of NOD2/CARD15, TLR and IL23R Polymorphisms on the Incidence of Infectious Complications in Allo-HSCT Recipients.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2201-2201
Author(s):  
Alexandra Maria Holowiecka-Goral ◽  
Sebastian Giebel ◽  
Jerzy Wojnar ◽  
Elzbieta Pietruszka ◽  
Agnieszka Karolczyk ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Infectious Complications ◽  
Individual Risk ◽  
Unrelated Donor ◽  
X Rays ◽  
Increased Risk ◽  
Card15 Gene ◽  
The Impact

Abstract BACKGROUND: Infections and graft-vs.-host disease (GvHD) remain the major obstacles for successful allogeneic stem cell transplantation (alloHSCT). As specific immune response is profoundly suppressed during the first months after transplantation, the components of innate immunity are expected to play important role in protection against infections and modulation of GvHD. The goal of this prospective study was to evaluate the impact of NOD2/CARD15 gene, toll-like receptors (TLR), and interleukin-23 receptor (IL-23R) single nucleotide polymorphisms (SNPs), on outcome of alloHSCT, including the incidence of infectious complications and acute GvHD. All these factors were documented to take part in innate immunity. PATIENTS: One-hundred-twenty-five consecutive patients, mainly with hematological malignancies, aged 32 (18–58)y, treated with alloHSCT from HLA-matched related (n=43) or matched unrelated donor (MUD) (n=82) were analyzed. The conditioning regimen was myeloablative, GVHD prophylaxis consisted of cyclosporin, metotrexate, and, in case of MUD-HSCT, pre-transplant anti-thymocyte globulin. METHODS: Donors and recipients were tested for SNP8,12,13 of the NOD2/CARD15 gene, TLR2/753, TLR4/299, TLR4/399, TLR5/C1174T, and TLR9/1635 SNPs, as well as IL23R/11209026 SNP. Study end-points included the incidence of bacterial, fungal and clinically relevant viral infections. Infections were recognized based on clinical symptoms, microbial cultures, chest X-rays for pneumonia confirmation and in case of CMV and EBV- PCR screening. We analyzed separately infections occurring in the early, cytopenic phase and those occurring after engraftment. Additionally, the incidence of acute GvHD and survival was evaluated. RESULTS: Presence of NOD2/CARD15 SNP8 in recipient resulted in higher frequency of neutropenic pneumonia (40% vs. 6%, p=0.045) and bacterial pharyngitis (100% vs. 50%, p=0.06), as well as increased incidence of grade III-IV acute GVHD (40% vs. 7%, p=0.05), which translated into increased non-relapse mortality (60% vs. 14%, p=0.005) and decreased 2-year overall survival (20% vs. 71%, p=0.003). TLR4/299 SNP in recipient tended to increase the risk of neutropenic fever (FUO) (67% vs. 30%, p=0.06) and decrease survival (71% vs. 48%, p=0.09). TLR2/753 SNP in donor was associated with higher incidence of FUO (83% vs. 30%, p-0.01), while TLR5/C1174T SNP in recipient resulted in increased incidence of EBV infection (25% vs. 4%, p-0.05). Presence of IL23R/11209026 SNP in donor tended to increase the incidence of neutropenic pneumonias (29% vs. 6%, p=0.09). CONCLUSIONS: NOD2/CARD15, TLR, and IL23R SNPs appear to influence outcome of alloHSCT contributing to increased incidence of infections, and in case of NOD2/CARD15 SNP8 in recipient to increased risk of severe acute GVHD. The genomic analysis may allow elaboration of adequate preventive strategies based on individual risk assessment. Our results encourage for further, extended studies.

The Impact of NOD2/CARD15 and KIR Polymorphisms on the Incidence of Infectious Complications in allo-HSCT Recipients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2968-2968
Author(s):  
Aleksandra Holowiecka-Goral ◽  
Sebastian Giebel ◽  
Izabela Nowak ◽  
Tomasz Czerw ◽  
Jerzy Wojnar ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Clinical Symptoms ◽  
Conditioning Regimen ◽  
Infectious Complications ◽  
Individual Risk ◽  
Unrelated Donor ◽  
Nucleotide Polymorphisms ◽  
Card15 Gene ◽  
Tract Infections ◽  
The Impact

Abstract BACKGROUND: Infections remain the major obstacle for successful allogeneic stem cell transplantation (alloHSCT). As specific immune response is profoundly suppressed during the first months after transplantation, the components of innate immunity are expected to play important role in anti-infectious responses. The goal of this prospective study was to evaluate the impact of NOD2/CARD15 gene single nucleotide polymorphisms (SNPs) as well as killer immunoglobulin-like receptors (KIRs), on the frequency of infectious complications after alloHSCT. NOD2/CARD15 protein is broadly expressed on epithelial cells, APCs and both B and T lymphocytes. KIRs regulate function of NK cells and a subset of T cells. Both were documented to take part in innate immunity. PATIENTS: One-hundred-two consecutive patients with hematological malignancies, aged 32 (18-58)y, treated with alloHSCT from HLA-matched related (n=34) or matched unrelated donor (MUD) (n=68) were included. The conditioning regimen was myeloablative, GVHD prophylaxis consisted of CsA, Mtx, and, in case of MUD-HSCT, pre-transplant ATG. METHODS: Donors and recipients were tested for SNP8,12,13 of the NOD2/CARD15 gene as well as 11 KIR genes. Study end-points included the incidence of G(+) and G(–) bacterial, fungal and clinically relevant viral infections. Infections were recognized based on clinical symptoms, microbial cultures and in case of CMV and EBV- PCR screening. Pneumonia was confirmed by radiograms. We analyzed separately infections occurring in the early, cytopenic phase and those occurring after engraftment. RESULTS: Presence of KIR2DS3 gene in the donor protected against bacterial pharyngitis (46% vs. 66%, p=0.05), whereas KIR2DS1 in the donor was associated with decreased incidence of pneumonia (12% vs. 32%, p=0.02). Presence of KIR2DS1 in the donor correlated with lower rate of EBV infection (0% vs. 10,2%, p=0.04). SNP8 of the NOD2/CARD15 gene in the recipient tended to increase the risk of severe bacterial pharyngitis (100% vs. 57%, p=0.08) and neutropenic pneumonia (40% vs 7%; p=0.06). As in our previous report there was a lower incidence of urinary tracts infection in NOD2/CARD15 SNPs carriers (32% vs. 59%; p=0.04). As well, NOD2/CARD15 SNPs carriers tended to be protected against HSV infections (0% vs. 9,6%, p=0.08). CONCLUSIONS: NOD2/CARD15 and KIR gene polymorphisms both influence the incidence of infections after alloHSCT. In particular, the effect of donor activating KIRs is generally protective while recipients with NOD2/CARD15 SNPs seems to more susceptible to respiratory tract infections. The genomic analysis may be useful for prediction of infectious complications. Pathogen-specific antibiotic and antiviral prophylaxis based on individual risk assessment may contribute to reduction of infection-related alloHSCT failures.

scholarly journals Invasive Fungal Infections and Targeted Therapies in Hematological Malignancies

2021 ◽  
Vol 7 (12) ◽  
pp. 1058
Author(s):  
Jessica S. Little ◽  
Zoe F. Weiss ◽  
Sarah P. Hammond
Keyword(s):  
Targeted Therapies ◽  
Hematological Malignancies ◽  
Fungal Infections ◽  
High Risk Patient ◽  
Underlying Disease ◽  
Infectious Complications ◽  
Invasive Fungal Infections ◽  
Individual Risk ◽  
Increased Risk ◽  
The Impact

The use of targeted biologic therapies for hematological malignancies has greatly expanded in recent years. These agents act upon specific molecular pathways in order to target malignant cells but frequently have broader effects involving both innate and adaptive immunity. Patients with hematological malignancies have unique risk factors for infection, including immune dysregulation related to their underlying disease and sequelae of prior treatment regimens. Determining the individual risk of infection related to any novel agent is challenging in this setting. Invasive fungal infections (IFIs) represent one of the most morbid infectious complications observed in hematological malignancy. In recent years, growing evidence suggests that certain small molecule inhibitors, such as BTK inhibitors and PI3K inhibitors, may cause an increased risk of IFI in certain patients. It is imperative to better understand the impact that novel targeted therapies might have on the development of IFIs in this high-risk patient population.

Impact of Prophylaxis with Aerosolized Amphotericin-B Deoxycholate (d-AmB) on Respiratory Tract Invasive Fungal Infections (IFIs) after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4986-4986
Author(s):  
Enrico Morello ◽  
Irene M. Cavattoni ◽  
Pietro Fabris ◽  
Silvia Coin ◽  
Barbara Amato ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Bacterial Infections ◽  
Fungal Infections ◽  
Unrelated Donor ◽  
X Rays ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Number Of Patients ◽  
Increased Risk ◽  
The Impact

Abstract Background and aims IFIs still pose major challenges in HSCT, and effective prophylaxis remains a matter of debate. The aim of this retrospective study was to evaluate the impact of aerosolized d-AmB on respiratory tract IFIs in a homogeneous cohort of allogeneic HSCT patients, transplanted at our institution. Patients and methods Since 1999, 81 consecutive patients were transplanted from matched related (N=61) or unrelated donor (MUD). Analysis was performed on 74 evaluable patients, in order to monitor the prevalence of respiratory tract IFIs within 40 days after HSCT, according to current guidelines (possible, probable, proven IFIs). Conventional antifungal prophylaxis was based on the association of fluconazole (400 mg/d), plus aerosolized d-AmB (15 mg bid) in 54 out of 74 cases (73%). All the patients were screened before transplant and monitored thereafter with CT or x-rays (paranasal sinuses, thorax), surveillance swabs and galactomannan antigenemia. Chi square test was performed to evaluate correlations between variables. Results Aerosolised d-AmB was administered to 70 patients for a median time of 15 days (range 1–45). Prolonged administration was not associated with increased severe bacterial infections, nor severe adverse events were observed; only a patient developed moderate bronchial spasm. In 13 pts, aerosolized d-AmB was delivered for less than 7 days, due to worsened clinical conditions, or poor compliance. In this group, proven IFIs were diagnosed in 2 patients (1 mucormycosis and 1 fusariosis), possible aspergillosis in one and probable aspergillosis in another one. A shortened administration (<7 days) of aerosolized d-AmB was associated with an increased risk of IFIs (p=0,002). Overall, 95% of patients did not experience IFIs and nobody died due to IFIs. Nine patients had a pre-transplant nasal swab positive for Aspergillus spp., and 8 of them received Aerosolized d-AmB; subsequent surveillance swabs proved negative. On the other hand, the only patient with positive swab who was not able to receive aerosolized d-AmB due to bronchial spasm developed a possible aspergillosis. Discussion Despite the low number of patients, prolonged aerosolized d-AmB seems to play a role in preventing respiratory tract IFIs, but a randomised controlled trial is recommended to verify the impact of this prophylaxis in the setting of allogeneic HSCT.

A Comparison of Stem Cell Source in Recipients of T-Cell Depleted Myeloablative Transplants for Leukaemia: No Difference in Mortality Using BM or PBSC.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 46-46
Author(s):  
B.E. Shaw ◽  
Nigel H. Russell ◽  
A. Pagliuca ◽  
J. Apperley ◽  
G. Cook ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Stem Cell Source ◽  
Increased Risk ◽  
Significant Difference ◽  
Cell Source ◽  
The Impact

Abstract The use of GSCF-mobilised Peripheral Blood Stem Cells (PBSC) for unrelated donor (UD) transplantation has increased dramatically since 2000. The association of PBSC with more rapid engraftment and with an increase in chronic Graft versus Host Disease (GvHD), compared to bone marrow (BM) has been reported in a number of studies. More recently the use of PBSC has been associated with an increase in transplant related mortality (TRM) and decrease in survival (OS) in T-cell replete transplants. We sought to analyse the impact of PBSC compared to BM in a cohort of UD transplant recipients, where T-cell depleting agents (in-vivo campath in >90%) were included in the transplant conditioning. The study included 145 patients transplanted between January 2000 and March 2006: CML- 35 in 1CP; acute leukaemia (AML in 61, ALL in 49)-110 in CR1 or 2. All had myeloablative conditioning regimens and received grafts with 9–10/10 matched HLA alleles. 86 patients received BM and 59 PBSC. There were no associations between the stem cell source and any transplant variable (including disease and stage). There was a trend to an increased use of PBSC in patients with a single antigen mismatch (p=0.052). All evaluable patients achieved neutrophil engraftment, with a significantly faster time to engraft in recipients of PBSC compared to BM (16 vs 20 days; p=0.0003). The incidence of acute GvHD was 46% (grade I in 50%, II in 41%, III in 8%, IV in 2%). This was significantly higher in recipients of PBSC (60%) compared to BM (36%; p=0.006), however there was no increase in either II/IV (p=0.69) or III/IV (p=0.18) disease in PBSC recipients. In univariate analysis, the presence of a single HLA mismatch (p=0.026) was the only other variable to be associated with an increase in acute GvHD. In a logistic regression model including both these variables, the use of PBSC remained significantly associated with an increase in aGvHD (OR=2.3; 95% CI 1.1,4.7;p=0.020). The TRM was 14%, 27% and 39% at 100 days, 1 and 5 years respectively. At none of these time points was the stem cell source associated with a significant difference in TRM. The 5-year incidence of chronic GvHD was 58% (BM 55%, PBSC 60%; NS), extensive disease in one third, and of relapse was 61% (BM 60%, PBSC 62%; NS). The 5-years OS was 41% with a median follow-up of 3.4 years (0.5–7.1). This was 44% using PBSC and 40% using BM (NS). In conclusion, although we observed an increase in acute GVHD with PBSC this was only of grade 1 disease. We found no association between the use of PBSC and an increased risk of chronic GVHD or of a worse transplant outcome, when compared to BM, in recipients of T-cell depleted myeloablative transplants for leukaemia.

The Impact of Rituximab in the Development of Acute Graft Versus Host Disease (GVHD) Following Allogeneic Stem Cell Transplantation (SCT) for Acute Lymphoblastic Leukemia (ALL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1803-1803
Author(s):  
Partow Kebriaei ◽  
Rima M. Saliba ◽  
Carrie Ma ◽  
Cindy Ippoliti ◽  
Daniel R. Couriel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Gvhd ◽  
Lymphoblastic Leukemia ◽  
Conditioning Regimen ◽  
Control Group ◽  
P Value ◽  
Unrelated Donor ◽  
Study Group ◽  
Donor Characteristics ◽  
The Impact

Abstract We investigated the safety and efficacy of administering rituximab in combination with a standard myeloablative conditioning regimen of cyclophosphamide (Cy, 60 mg/kg daily x 2 doses) and total body irradiation (TBI, 12 Gy in four daily fractions) with allogeneic SCT in adult patients (pts) with ALL. Pts were eligible if their disease expressed CD20 in &gt;20% blasts by flow cytometry. Rituximab was administered at 375 mg/m2 on days 6, −1, +7 and +14 following stem cell infusion. 24 pts were entered on study. The results were retrospectively compared with those of a historical control group of 31 pts receiving the same preparative regimen without rituximab. The two treatment groups had similar numbers of matched sibling and unrelated donor grafts. Pt and donor characteristics are detailed in Table 1. GVHD prophylaxis consisted of tacrolimus and methotrexate for nearly all pts in both study and control groups; 4 pts in the control group and 1 pt in the study group received pentostatin in addition to tacrolimus and methotrexate. Preliminary data suggests that pentostatin reduces the incidence of acute GVHD (de Lima et al. Blood2004;104:727a). The cumulative incidence of non-relapse mortality (NRM) at 2 years was 18% for the study group and 33% for the controls. There was no delay in engraftment or increased incidence of infection in pts treated with rituximab. Despite the greater use of pentostatin in the control group, the incidence of grade II–IV acute GVHD tended to be lower in pts treated with rituximab as compared to controls: 17% vs. 39%, p=0.07. The incidence of chronic extensive GVHD was not significantly different between the two groups: 37% vs. 34%, p=0.7. OS at 2 years was 45% for the study group and 38% for the controls, p=0.5. PFS at 2 years was 31% for the study group and 38% for the control group, p=0.8. Treatment outcomes are summarized in Table 1. In conclusion, our results demonstrate that the addition of rituximab to standard Cy/TBI conditioning for allogeneic SCT in ALL is associated with a relatively low rate of acute GVHD and NRM. Differences in pt characteristics preclude direct comparison. However, there is no apparent benefit for the addition of rituximab on disease relapse. Table 1. Patient, Donor Characteristics, and Outcomes Cy/TBI/rituximab No. pts Cy/TBI No. pts P-value 1. Donor age missing for 1 pt in each treatment group. Total Pts 24 31 Median Recipient Age, yrs (range 30 (18–54) 35 (18–53) Median Pt Age, yrs (range)1 38 (15–53) 36 (14–54) Donor Type (%) Matched related 15 (62) 21 (68) Matched unrelated 9 (38) 10 (32) 0.7 Stem Cell Source (%) BM 9 (38) 17 (55) PB 15 (62) 14 (45) 0.2 Sex donor/pt mismatch (%) 8 (33) 12 (40) 0.7 CMV donor/pt mismatch (%) 10 (43) 12 (40) 0.8 ABO donor/pt mismatch (%) 14 (58) 10 (33) 0.05 Graft Composition, median (range) Total nucleated cells (x108/kg) 4 (1–14) 4 (1–9) 0.6 CD34+(x106/kg) 5 (1–9) 5 (2–8) 0.9 CD3+ (x106/kg) 110 (8–370) 37 (5–286) 0.2 Disease Status at SCT (%) CR1 6 (25) 17 (54) Remission, beyond CR1 13 (54) 7 (23) Not in Remission 5 (21) 7 (23) 0.03 Acute GVHD II–IV 17% 39% 0.07 Chronic Extensive GVHD 37% 34% 0.7 OS, 2 yrs 45% 37% 0.5 PFS, 2 yrs 31% 38% 0.8

SNP12 and SNP13 Variants of NOD2/CARD15 Gene of Donor and Recipient as Independent Risk Factors for Severe Intestinal and Pulmonary GVHD after Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3242-3242
Author(s):  
Alexandra Holowiecka-Goral ◽  
Jerzy Wojnar ◽  
Sebastian Giebel ◽  
Elzbieta Grudziecka ◽  
Malgorzata Oczko ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Card15 Gene ◽  
The Impact ◽  
Grade Iii

Abstract Background: Presence of any of single nucleotide polymorphism (SNPs) of the NOD2/CARD15 gene have been recently proven to correlate with higher rate of GvHD after allogeneic hematopoietic stem cell transplantation - alloHSCT (Holler E et al; Blood2006,107,4189). Mutated variants lead to impaired antibacterial response. As NOD2/CARD15 is expressed not only in monocytets/macrophages but also in both intestinal and bronchial epithelial cells these organs seem to be a major target for developing advanced GvHD. Patients and methods: The impact of each single donor (D) and recipient (R) SNPs (8,12,13) of NOD2/CARD15 gene on the incidence of acute GvHD (grade II-IV, grade III-IV, intestinal), chronic GvHD (overall, extensive, pulmonary), survival, and non-relapse mortality was evaluated in a setting of 72 patients treated with alloHSCT in single BMT center in Katowice between Jan 2000 and Jun 2005. Median patient age was 33 (11–52) years. In 70/72 cases hematological malignancies were indication for alloHSCT. Conditioning regimen was myeloablative in all cases, bone marrow was used as the only source of stem cells in 74% of patients. GVHD prophylaxis consisted of CsA, Mtx and, in case of URD-HSCT - antithymocyte globulin. Results: In univariate and multivariate analysis, including other potential risk factors, the presence of SNP12 in the recipient was associated with increased incidence of intestinal acute GVHD (75% vs. 29%; RR 4,37, p=0,03), overall chronic GVHD (100% vs. 50%, RR 4,72; p=0,003), extensive chronic GVHD (80% vs. 24%; RR 5,12; p=0,02), and pulmonary chronic GVHD (47% vs. 9%; RR 5,97; p=0,02). SNP13 in the recipient resulted in increased incidence of grade III–IV acute GVHD (45% vs. 12%; RR 4,66; p=0,01), intestinal acute GVHD (64% vs. 24%; RR 4,21, p=0,005), and extensive chronic GVHD (55% vs. 25%; RR 3,59; p=0,03). SNP13D in the donor contributed to increased risk of pulmonary chronic GVHD (36% vs. 8%; RR 6,58; p=0,01). In this single centre analysis we were not able to demonstrate the impact of NOD2/CARD15 SNPs on survival. Conclusion: The presence of particular mutations of NOD2/CARD15 in the recipient and/or the donor is associated with increased risk of severe acute and chronic GVHD. In particular, intestines and lungs appear to be target organs of these complications. Our findings may contribute to optimization of immunosuppressive and gastrointestinal decontamination regimens based on individual risk assessment for GVHD.

Unrelated Allogeneic Stem Cell Transplantation for Severe Acquired Aplastic Anemia: Has Outcome Improved?.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3105-3105 ◽  
Author(s):  
Sebastien Maury ◽  
M.-Lorraine Balere-Appert ◽  
Zina Chir ◽  
J.-Michel Boiron ◽  
Claire Galambrun ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Aplastic Anemia ◽  
Graft Failure ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Young Patients ◽  
Unrelated Donor ◽  
Hla Matching ◽  
The Impact

Abstract We aimed to determine whether outcome of HSCT from an unrelated donor has improved over time for patients with severe acquired aplastic anemia (SAA) and, if so, to determine whether improvement resulted from changes in patient selection, changes in transplantation technique, or both. We thus analyzed the outcome of 89 patients (median age 17 years, range 0–52) who received such transplantations between 1989 and 2004. We compared two cohorts of patients transplanted within two successive time-periods (1989–1998 and 1999–2004) associated with probabilities (± 95% confidence interval) of 5-year survival significantly different: 29% ± 7% and 50% ± 7%, respectively (P<.01, Figure 1). Significant differences between the two cohorts concerned transplant-related, but not patient- and disease-related variables: the use of ATG and of fludarabine within conditioning and HLA matching at the allelic level for the 10 HLA-A, -B, -C, -DRB1 and -DQB1 loci (P=.0004) were more frequent in the recent 1999–2004 period. In multivariate analysis, the only 2 factors influencing survival were HLA allelic matching (P<.01) and younger age of recipient (<17 years, P<.0001). Of note, the impact of HLA matching disappeared in multivariate analysis when it was considered at the antigenic level for HLA-A, -B and -DR antigens, which underlines the importance of considering HLA matching at the allelic rather than the generic level for these transplantations. Survival reached 78% ± 11% at 5-year for the younger patients fully HLA-matched (n=14), which can be compared with survivals obtained for HLA-identical sibling transplants in similar young patients. Cumulative incidences of graft failure, grade II–IV or grade III–IV acute GVHD, and chronic GVHD were: 14% ± 4 % at 2 years, 50% ± 5 % and 24% ± 4 % at 100 days, and 28% ± 5 % at 2 years after HSCT (limited: 17% ± 4 %, extensive: 11% ± 3 %), respectively. In a competing risk analysis, allelic HLA matching - particularly incorporating HLA-C but not -DQB1 matching - but also a high cell-dose injected (> 2,6.108/kg nucleated cells, the median value of the cohort) and the use of fludarabine and/or ATG in the conditioning regimen were found as protective against graft failure and acute GVHD, respectively. Our results suggest that survival after unrelated transplantation for SAA has improved over the past 15 years, due to a better HLA matching at the allelic level for both HLA class I and class II antigens, but also to other transplant-related factors. Figure 1 Figure 1.

scholarly journals Prediction of sepsis-related outcomes in neonates through systematic genotyping of polymorphisms in genes for innate immunity and inflammation: a narrative review and critical perspective

2013 ◽  
Vol 131 (5) ◽  
pp. 338-350 ◽  
Author(s):  
Juliana Kilesse Carvalho ◽  
Daniella Batalha Moore ◽  
Ricardo Alves Luz ◽  
Pedro Paulo Xavier-Elsas ◽  
Maria Ignez Capella Gaspar-Elsas
Keyword(s):  
Innate Immunity ◽  
Gene Polymorphisms ◽  
Large Scale ◽  
Scientific Evidence ◽  
Cochrane Library ◽  
Increased Risk ◽  
Immunity Genes ◽  
Hemostatic Factors ◽  
Narrative Literature Review ◽  
The Impact

CONTEXT AND OBJECTIVE: Neonatal sepsis is associated with premature birth and maternal infection. Large-scale studies seek to define markers that identify neonates at risk of developing sepsis. Here, we examine whether the scientific evidence supports systematic use of polymorphism genotyping in cytokine and innate immunity genes, to identify neonates at increased risk of sepsis. DESIGN AND SETTING: Narrative literature review conducted at Fernandes Figueira Institute, Brazil. METHODS: The literature was searched in PubMed, Embase (Excerpta Medica Database), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde), SciELO (Scientific Electronic Library Online) and Cochrane Library. From > 400,000 references, 548 were retrieved based on inclusion/exclusion criteria; 22 were selected for detailed analysis after quality assessment. RESULTS: The studies retrieved addressed the impact of gene polymorphisms relating to immune mechanisms (most often TNF-a, LT-a, IL-6, IL-1β, IL-1ra, L-selectin, CD14 and MBL) or inflammatory mechanisms (ACE and angiotensin II receptors; secretory PLA2; and hemostatic factors). Despite initial reports suggesting positive associations between specific polymorphisms and increased risk of sepsis, the accumulated evidence has not confirmed that any of them have predictive power to justify systematic genotyping. CONCLUSIONS: Sepsis prediction through systematic genotyping needs to be reevaluated, based on studies that demonstrate the functional impact of gene polymorphisms and epidemiological differences among ethnically distinct populations.

scholarly journals Association of ABO haplotypes with the risk of venous thrombosis: impact on disease risks estimation

Blood ◽  
2020 ◽  
Author(s):  
Louisa Goumidi ◽  
Florian Thibord ◽  
Kerri L. Wiggins ◽  
Ruifang Li-Gao ◽  
Michael R Brown ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Blood Group ◽  
Plasma Levels ◽  
Odds Ratio ◽  
Prediction Models ◽  
Genetic Risk Score ◽  
Individual Risk ◽  
Abo Blood Group ◽  
Increased Risk ◽  
The Impact

Genetic risk score (GRS) analysis is an increasingly popular approach to derive individual risk prediction models for complex diseases. In the context of venous thrombosis (VT), any GRS shall integrate information at the ABO blood group locus, the latter being one of the major susceptibility locus for this disease. However, there is yet no consensus about which single nucleotide polymorphisms (SNPs) must be investigated when one is interested in properly assessing the association of ABO locus with VT risk. Using comprehensive haplotype analyses of ABO blood group tagging SNPs in up to 5,425 cases and 8,445 controls from 6 studies, we demonstrated that using only rs8176719 (tagging O1) to correctly assess the impact of ABO locus on VT risk is suboptimal as 5% of rs8176719-delG carriers are not exposed at higher VT risk. Instead, we recommend to use 4 SNPs, rs2519093 (tagging A1), rs1053878 (A2), rs8176743 (B) and rs41302905 (O2) in any analysis aimed at assessing the impact of ABO locus on VT risk to avoid any risk misestimation. Compared to O1 haplotype that can be inferred from these 4 SNPs, the A2 haplotype is associated with a modest increase in VT risk (odds ratio ~1.2), A1 and B haplotypes are associated with a ~1.8 fold increased risk while O2 tend to be slightly protective (odds ratio ~0.80). In addition, our analyses clearly showed that while the A1 an B blood group are associated with increased vWF and FVIII plasma levels only the A1 blood group is associated wih ICAM plasma levels but in an opposite direction, leaving additional avenues to be explored in order to fully understand the whole spectrum of biological effect of ABO locus on cardiovascular traits.

Allogeneic Leukocyte-Reduced Red Blood Cell Transfusion Is Associated with Postoperative Infectious Complications and Cancer Recurrence after Colon Cancer Resection

2019 ◽  
Vol 37 (2) ◽  
pp. 163-170 ◽  
Author(s):  
Andrew-Paul Deeb ◽  
Christopher T. Aquina ◽  
John R.T. Monson ◽  
Neil Blumberg ◽  
Adan Z. Becerra ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Cancer Recurrence ◽  
Infectious Complications ◽  
Oncologic Outcomes ◽  
Red Blood Cell Transfusion ◽  
Elective Resection ◽  
Increased Risk ◽  
The Impact

Background/Aims: Transfusion rates in colon cancer surgery are traditionally very high. Allogeneic red blood cell (RBC) transfusions are reported to induce immunomodulation that contributes to infectious morbidity and adverse oncologic outcomes. In an effort to attenuate these effects, the study institution implemented a universal leukocyte reduction protocol. The purpose of this study was to examine the impact of leukocyte-reduced (LR) transfusions on postoperative infectious complications, recurrence-free survival, and overall survival (OS). Methods: In a retrospective study, patients with stage I–III adenocarcinoma of the colon from 2003 to 2010 who underwent elective resection were studied. The primary outcome measures were postoperative infectious complications and recurrence-free and OS in patients that received a transfusion. Bivariate and multivariable regression analyses were performed for each endpoint. Results: Of 294 patients, 66 (22%) received a LR RBC transfusion. After adjustment, transfusion of LR RBCs was found to be independently associated with increased infectious complications (OR 3.10, 95% CI 1.24–7.73), increased odds of cancer recurrence (hazard ratio [HR] 3.74, 95% CI 1.94–7.21), and reduced OS when ≥3 units were administered (HR 2.24, 95% CI 1.12–4.48). Conclusion: Transfusion of LR RBCs is associated with an increased risk of infectious complications and worsened survival after elective surgery for colon cancer, irrespective of leukocyte reduction.

Sign in / Sign up

Export Citation Format

Share Document