PARAMETERS OF PROTEIN METABOLISM AND THYROID FUNCTION AS PREDICTORS OF A SCORING SYSTEM FOR ACUTE AND CHRONIC GRAFT-VERSUS-HOST DISEASE
(Abstract release date: 05/19/16)
EHA Library. Skert C. 06/09/16; 133067; E1518
Dr. Cristina Skert
Contributions
Contributions
Abstract
Abstract: E1518
Type: Eposter Presentation
Background
Some “classical” patient-, donor- and transplant characteristics, such as age, gender disparity, donor type, HLA-match, and source of stem cells, have been reported as predictors for acute and chronic GVHD. However, no studies analysed these “classical” variables together with parameters of metabolic and endocrine functions that may potentially influence the immune system.
Aims
Patient-and transplant variables together with index of liver and thyroid function, and some parameters of protein and lipid metabolism were retrospectively evaluated at different time points after transplantation, in order to identify possible predictors of acute and chronic GVHD and to calculate a risk score.
Methods
Clinical and transplant characteristics, number and type of infections before and after SCT were analysed in 200 patients. The following variables were also analysed pre-SCT, at day +7,+14,+21,+28, at + 3 and +6 months: LDH, parameters of liver function; parameters of protein and lipid metabolism; thyroid function tests; autoimmune parameters; body mass index. A 2-step multivariate analysis was performed using principal component analysis and Cox regression analysis. Based on the regression coefficient of Cox analysis for each significant predictor, a scoring system for acute and chronic GVHD was calculated.
Results
In multivariate analysis, diagnosis of Myelodisplastic Syndrome or Chronic Myeloid Leukemia (p=0.0004), conditioning regimen including Total Body Irradiation (p=0.0003), and pre transplantation urea > 34 mg/dl with +21 day urea > 54 mg/dl (p=0.0008) were predictors for acute GVHD. Score values for each factor are 2, 1, 1, respectively and the system had a score range between 0 and 4. The probabilities of acute GVHD according to the sum scores ranged from 8% (score 0) to 98% (score 4). Female donor (p=0.0008), pre-SCT TSH values ≥ 2 mU/L with +28 day urea ≥ 39 mg/dl (p=0.02), +6 month total protein < 5,5 g/dl with gamma-GT ≥ 347 U/L (p=0.0001) resulted predictors for moderate/severe chronic GVHD. Risk of chronic GVHD at +6,5 month ranged from 3% (score 0) to 97% (score 4).
Conclusion
Our study evidenced that factors other than those “classical” may be associated to GVHD. The scoring system included routine-parameters, which are easily available in clinical practice. Urea levels depend on the balance between protein intake, endogenous catabolism and urinary excretion. The inflammatory microenvironment of GVHD promotes muscle catabolism and hence, increased urea levels. Increased urea levels could be indirect index of increased uremic toxins as well, which may stimulate the production of pro-inflammatory cytokines and the activation of leukocytes. Increased urea levels and uremic toxins could also derive from a dysregulated metabolism of the gut microbiome that may influence immune system. Our findings suggest the usefulness to study in deep the complex network between metabolic/endocrine functions and immune system for a holistic approach of the transplant management.
Session topic: E-poster
Keyword(s): Graft-versus-host disease (GVHD), Risk factor
Type: Eposter Presentation
Background
Some “classical” patient-, donor- and transplant characteristics, such as age, gender disparity, donor type, HLA-match, and source of stem cells, have been reported as predictors for acute and chronic GVHD. However, no studies analysed these “classical” variables together with parameters of metabolic and endocrine functions that may potentially influence the immune system.
Aims
Patient-and transplant variables together with index of liver and thyroid function, and some parameters of protein and lipid metabolism were retrospectively evaluated at different time points after transplantation, in order to identify possible predictors of acute and chronic GVHD and to calculate a risk score.
Methods
Clinical and transplant characteristics, number and type of infections before and after SCT were analysed in 200 patients. The following variables were also analysed pre-SCT, at day +7,+14,+21,+28, at + 3 and +6 months: LDH, parameters of liver function; parameters of protein and lipid metabolism; thyroid function tests; autoimmune parameters; body mass index. A 2-step multivariate analysis was performed using principal component analysis and Cox regression analysis. Based on the regression coefficient of Cox analysis for each significant predictor, a scoring system for acute and chronic GVHD was calculated.
Results
In multivariate analysis, diagnosis of Myelodisplastic Syndrome or Chronic Myeloid Leukemia (p=0.0004), conditioning regimen including Total Body Irradiation (p=0.0003), and pre transplantation urea > 34 mg/dl with +21 day urea > 54 mg/dl (p=0.0008) were predictors for acute GVHD. Score values for each factor are 2, 1, 1, respectively and the system had a score range between 0 and 4. The probabilities of acute GVHD according to the sum scores ranged from 8% (score 0) to 98% (score 4). Female donor (p=0.0008), pre-SCT TSH values ≥ 2 mU/L with +28 day urea ≥ 39 mg/dl (p=0.02), +6 month total protein < 5,5 g/dl with gamma-GT ≥ 347 U/L (p=0.0001) resulted predictors for moderate/severe chronic GVHD. Risk of chronic GVHD at +6,5 month ranged from 3% (score 0) to 97% (score 4).
Conclusion
Our study evidenced that factors other than those “classical” may be associated to GVHD. The scoring system included routine-parameters, which are easily available in clinical practice. Urea levels depend on the balance between protein intake, endogenous catabolism and urinary excretion. The inflammatory microenvironment of GVHD promotes muscle catabolism and hence, increased urea levels. Increased urea levels could be indirect index of increased uremic toxins as well, which may stimulate the production of pro-inflammatory cytokines and the activation of leukocytes. Increased urea levels and uremic toxins could also derive from a dysregulated metabolism of the gut microbiome that may influence immune system. Our findings suggest the usefulness to study in deep the complex network between metabolic/endocrine functions and immune system for a holistic approach of the transplant management.
Session topic: E-poster
Keyword(s): Graft-versus-host disease (GVHD), Risk factor
Abstract: E1518
Type: Eposter Presentation
Background
Some “classical” patient-, donor- and transplant characteristics, such as age, gender disparity, donor type, HLA-match, and source of stem cells, have been reported as predictors for acute and chronic GVHD. However, no studies analysed these “classical” variables together with parameters of metabolic and endocrine functions that may potentially influence the immune system.
Aims
Patient-and transplant variables together with index of liver and thyroid function, and some parameters of protein and lipid metabolism were retrospectively evaluated at different time points after transplantation, in order to identify possible predictors of acute and chronic GVHD and to calculate a risk score.
Methods
Clinical and transplant characteristics, number and type of infections before and after SCT were analysed in 200 patients. The following variables were also analysed pre-SCT, at day +7,+14,+21,+28, at + 3 and +6 months: LDH, parameters of liver function; parameters of protein and lipid metabolism; thyroid function tests; autoimmune parameters; body mass index. A 2-step multivariate analysis was performed using principal component analysis and Cox regression analysis. Based on the regression coefficient of Cox analysis for each significant predictor, a scoring system for acute and chronic GVHD was calculated.
Results
In multivariate analysis, diagnosis of Myelodisplastic Syndrome or Chronic Myeloid Leukemia (p=0.0004), conditioning regimen including Total Body Irradiation (p=0.0003), and pre transplantation urea > 34 mg/dl with +21 day urea > 54 mg/dl (p=0.0008) were predictors for acute GVHD. Score values for each factor are 2, 1, 1, respectively and the system had a score range between 0 and 4. The probabilities of acute GVHD according to the sum scores ranged from 8% (score 0) to 98% (score 4). Female donor (p=0.0008), pre-SCT TSH values ≥ 2 mU/L with +28 day urea ≥ 39 mg/dl (p=0.02), +6 month total protein < 5,5 g/dl with gamma-GT ≥ 347 U/L (p=0.0001) resulted predictors for moderate/severe chronic GVHD. Risk of chronic GVHD at +6,5 month ranged from 3% (score 0) to 97% (score 4).
Conclusion
Our study evidenced that factors other than those “classical” may be associated to GVHD. The scoring system included routine-parameters, which are easily available in clinical practice. Urea levels depend on the balance between protein intake, endogenous catabolism and urinary excretion. The inflammatory microenvironment of GVHD promotes muscle catabolism and hence, increased urea levels. Increased urea levels could be indirect index of increased uremic toxins as well, which may stimulate the production of pro-inflammatory cytokines and the activation of leukocytes. Increased urea levels and uremic toxins could also derive from a dysregulated metabolism of the gut microbiome that may influence immune system. Our findings suggest the usefulness to study in deep the complex network between metabolic/endocrine functions and immune system for a holistic approach of the transplant management.
Session topic: E-poster
Keyword(s): Graft-versus-host disease (GVHD), Risk factor
Type: Eposter Presentation
Background
Some “classical” patient-, donor- and transplant characteristics, such as age, gender disparity, donor type, HLA-match, and source of stem cells, have been reported as predictors for acute and chronic GVHD. However, no studies analysed these “classical” variables together with parameters of metabolic and endocrine functions that may potentially influence the immune system.
Aims
Patient-and transplant variables together with index of liver and thyroid function, and some parameters of protein and lipid metabolism were retrospectively evaluated at different time points after transplantation, in order to identify possible predictors of acute and chronic GVHD and to calculate a risk score.
Methods
Clinical and transplant characteristics, number and type of infections before and after SCT were analysed in 200 patients. The following variables were also analysed pre-SCT, at day +7,+14,+21,+28, at + 3 and +6 months: LDH, parameters of liver function; parameters of protein and lipid metabolism; thyroid function tests; autoimmune parameters; body mass index. A 2-step multivariate analysis was performed using principal component analysis and Cox regression analysis. Based on the regression coefficient of Cox analysis for each significant predictor, a scoring system for acute and chronic GVHD was calculated.
Results
In multivariate analysis, diagnosis of Myelodisplastic Syndrome or Chronic Myeloid Leukemia (p=0.0004), conditioning regimen including Total Body Irradiation (p=0.0003), and pre transplantation urea > 34 mg/dl with +21 day urea > 54 mg/dl (p=0.0008) were predictors for acute GVHD. Score values for each factor are 2, 1, 1, respectively and the system had a score range between 0 and 4. The probabilities of acute GVHD according to the sum scores ranged from 8% (score 0) to 98% (score 4). Female donor (p=0.0008), pre-SCT TSH values ≥ 2 mU/L with +28 day urea ≥ 39 mg/dl (p=0.02), +6 month total protein < 5,5 g/dl with gamma-GT ≥ 347 U/L (p=0.0001) resulted predictors for moderate/severe chronic GVHD. Risk of chronic GVHD at +6,5 month ranged from 3% (score 0) to 97% (score 4).
Conclusion
Our study evidenced that factors other than those “classical” may be associated to GVHD. The scoring system included routine-parameters, which are easily available in clinical practice. Urea levels depend on the balance between protein intake, endogenous catabolism and urinary excretion. The inflammatory microenvironment of GVHD promotes muscle catabolism and hence, increased urea levels. Increased urea levels could be indirect index of increased uremic toxins as well, which may stimulate the production of pro-inflammatory cytokines and the activation of leukocytes. Increased urea levels and uremic toxins could also derive from a dysregulated metabolism of the gut microbiome that may influence immune system. Our findings suggest the usefulness to study in deep the complex network between metabolic/endocrine functions and immune system for a holistic approach of the transplant management.
Session topic: E-poster
Keyword(s): Graft-versus-host disease (GVHD), Risk factor
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