Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard &...
-
Upload
elyse-gulliford -
Category
Documents
-
view
217 -
download
0
Transcript of Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard &...
![Page 1: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/1.jpg)
Immune Recovery in Children after Bone Marrow Transplant
Rollo Hoare
Supervisors:
Robin Callard & Joseph Standing
![Page 2: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/2.jpg)
Bone Marrow Transplant (BMT)
• BMT done post leukemia or other immune system failure
• Before BMT patients undergo conditioning during which all lymphocytes in the body may be killed
• We are looking at the recovery of the immune system after BMT
• In particular the concentration of CD4 in the blood
![Page 3: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/3.jpg)
The aim of the project
1. Build a model for the CD4 cell count recovery
2. Fit the model to the data (CD4 count time series)
3. Add parameters related to covariates
4. Analyse results of included covariates
![Page 4: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/4.jpg)
The aim of the project
1. Build a model for the CD4 cell count recovery
2. Fit the model to the data (CD4 count time series)
3. Add parameters related to covariates
4. Analyse results of included covariates
![Page 5: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/5.jpg)
1. The Model
• Start with an exponential model:
asy
int
Parametersasy = asymptoteint = interceptc = rate of change
![Page 6: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/6.jpg)
The aim of the project
1. Build a model for the CD4 cell count recovery
2. Fit the model to the data (CD4 count time series)
3. Add parameters related to covariates
4. Analyse results of included covariates
![Page 7: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/7.jpg)
2. Fit model to dataa) Age adjustment• CD4 count drops non-linearly with age in healthy
children
![Page 8: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/8.jpg)
2. Fit model to dataNLME Modelling•
![Page 9: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/9.jpg)
The aim of the project
1. Build a model for the CD4 cell count recovery
2. Fit the model to the data (CD4 count time series)
3. Add parameters related to covariates
4. Analyse results of included covariates
![Page 10: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/10.jpg)
3. Add covariates • Multivariate analysis: we add covariate
parameters into the model for:- BMT Age- Sex - BMT Number- Donor type- Donor cells type- Leukaemia- HCMV- EBV- Alem/anti-CD45/ATG
- Total body irradiation- Cyclosporine- Methotrexate- Mycophenolate- Prednisone- Muromonab- No conditioning- Reduced conditioning- Chimerism
![Page 11: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/11.jpg)
3. Diagnostic Plots
![Page 12: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/12.jpg)
3. Diagnostic Plots
![Page 13: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/13.jpg)
The aim of the project
1. Build a model for the CD4 cell count recovery
2. Fit the model to the data (CD4 count time series)
3. Add parameters related to covariates
4. Analyse results of included covariates
![Page 14: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/14.jpg)
4. Results• After SCM, we included the following covariates:
• Int:- Alemtuzumab/Anti-CD45/Anti-thymocyte Globulin- Leukaemia- Donor type
• Asy:- HCMV- No conditioning
• c:- Mycophenolate
![Page 15: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/15.jpg)
4. Results• Int: Alem/anti-CD45/ATG
![Page 16: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/16.jpg)
4. Results• Int: Leukaemia
![Page 17: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/17.jpg)
4. Results• Int: Donor type
![Page 18: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/18.jpg)
4. Results• Asy: HCMV
![Page 19: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/19.jpg)
4. Results• Asy: Conditioning
![Page 20: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/20.jpg)
4. Results• C: Mycophenolate
![Page 21: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/21.jpg)
Next Steps• Include age adjustment in the model rather than pre-
adjustment- Linear- Free exponential- Fixed exponential- Fixed exponential with ratio
• Or use another form of age adjustment- Square root ratio- Fourth root ratio
• Add in further covariates for conditioning drugs and diagnoses
• Look at dosage information
![Page 22: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/22.jpg)
Next StepsInclude age in model: Linear
• ASY = THETA(1) + THETA(2) * (3650-AGE)
![Page 23: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/23.jpg)
Next StepsInclude age in model: Linear
• ASY = THETA(1) + THETA(2) * (3650-AGE)
![Page 24: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/24.jpg)
Next StepsInclude age in model: Free exponential
• ASY = THETA(1) +THETA(2) * EXP(-THETA(3)*AGE)
![Page 25: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/25.jpg)
Next StepsInclude age in model: Free exponential
• ASY = THETA(1) +THETA(2) * EXP(-THETA(3)*AGE)
![Page 26: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/26.jpg)
Next StepsInclude age in model: Fixed exponential
• ASY = 924.2 + 23545.* EXP(-0.00101*AGE)
![Page 27: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/27.jpg)
Next StepsInclude age in model: Fixed exponential
• ASY = 924.2 + 23545.* EXP(-0.00101*AGE)
![Page 28: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/28.jpg)
Next StepsInclude age in model: Fixed exponential with ratio
• ASY = THETA(1) * (924.2 + 2355* EXP(-0.00101*AGE))
![Page 29: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/29.jpg)
Next StepsInclude age in model: Fixed exponential with ratio
• ASY = THETA(1) * (924.2 + 2355* EXP(-0.00101*AGE))
![Page 30: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/30.jpg)
Next StepsAge adjustment: Fourth root ratio
![Page 31: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/31.jpg)
Next StepsAdditional Covariates to be tested
- BMT Failure- Alemtuzumab- Anti CD-45- Anti-thymocyte globulin- Busulphan- Cyclosporine
(Conditioning)- Melphalan
- Fludarabine- Treosulphan- Diagnosis- Edited EBV- Edited HCMV- Edited donor cells- Edited donor type
![Page 32: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/32.jpg)
Conclusion• We have modelled the CD4 count recovery of children
post BMT using the logratio• We have found the following covariates affect recovery:
- Int: Alem/anti-CD45/ATG, Leukaemia, donor type
- Asy: Conditioning, HCMV
- c: mycophenolate• More work needs to be done to ascertain the reliability
of these results.
![Page 33: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/33.jpg)
Questions??
![Page 34: Immune Recovery in Children after Bone Marrow Transplant Rollo Hoare Supervisors: Robin Callard & Joseph Standing.](https://reader036.fdocuments.net/reader036/viewer/2022062423/56649cb45503460f949783ce/html5/thumbnails/34.jpg)