The impact of CD34+ cell dose on engraftment after SCTs: personalized estimates based on mathematical modeling
It is known that the number of transplanted cells has a significant impact on the outcome after SCT. We identify issues that cannot be addressed by conventional analysis of clinical trials and ask whether it is possible to develop a refined analysis to conclude about the outcome of individual patien...
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| Veröffentlicht in: | Bone marrow transplantation (Basingstoke) 2014-01, Vol.49 (1), p.30-37 |
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| creator | Stiehl, T Ho, A D Marciniak-Czochra, A |
| description | It is known that the number of transplanted cells has a significant impact on the outcome after SCT. We identify issues that cannot be addressed by conventional analysis of clinical trials and ask whether it is possible to develop a refined analysis to conclude about the outcome of individual patients given clinical trial results. To accomplish this, we propose an interdisciplinary approach based on mathematical modeling. We devise and calibrate a mathematical model of short-term reconstitution and simulate treatment of large patient groups with random interindividual variation. Relating model simulations to clinical data allows quantifying the effect of transplant size on reconstitution time in the terms of patient populations and individual patients. The model confirms the existence of lower bounds on cell dose necessary for secure and efficient reconstitution but suggests that for some patient subpopulations higher thresholds might be appropriate. Simulations demonstrate that relative time gain because of increased cell dose is an ‘interpersonally stable’ parameter, in other words that slowly engrafting patients profit more from transplant enlargements than average cases. We propose a simple mathematical formula to approximate the effect of changes of transplant size on reconstitution time. |
| doi_str_mv | 10.1038/bmt.2013.138 |
| format | Article |
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We identify issues that cannot be addressed by conventional analysis of clinical trials and ask whether it is possible to develop a refined analysis to conclude about the outcome of individual patients given clinical trial results. To accomplish this, we propose an interdisciplinary approach based on mathematical modeling. We devise and calibrate a mathematical model of short-term reconstitution and simulate treatment of large patient groups with random interindividual variation. Relating model simulations to clinical data allows quantifying the effect of transplant size on reconstitution time in the terms of patient populations and individual patients. The model confirms the existence of lower bounds on cell dose necessary for secure and efficient reconstitution but suggests that for some patient subpopulations higher thresholds might be appropriate. Simulations demonstrate that relative time gain because of increased cell dose is an ‘interpersonally stable’ parameter, in other words that slowly engrafting patients profit more from transplant enlargements than average cases. We propose a simple mathematical formula to approximate the effect of changes of transplant size on reconstitution time.</description><identifier>ISSN: 0268-3369</identifier><identifier>EISSN: 1476-5365</identifier><identifier>DOI: 10.1038/bmt.2013.138</identifier><identifier>PMID: 24056742</identifier><identifier>CODEN: BMTRE9</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/114/2397 ; 631/250/1904 ; 631/61/51/1844 ; Adolescent ; Adult ; Aged ; Algorithms ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Antigens, CD34 - metabolism ; Biological and medical sciences ; Bone marrow ; Bone marrow transplantation ; Bone marrow, stem cells transplantation. Graft versus host reaction ; Cell Biology ; Child ; Child, Preschool ; Clinical trials ; Clinical Trials as Topic ; Computer Simulation ; Cytokines - metabolism ; Hematology ; Hematopoietic Stem Cell Transplantation - methods ; Hematopoietic stem cells ; Humans ; Infant ; Internal Medicine ; Mathematical models ; Medical research ; Medical sciences ; Medicine ; Medicine & Public Health ; Medicine, Experimental ; Middle Aged ; Models, Theoretical ; Neutrophils - cytology ; original-article ; Public Health ; Reproducibility of Results ; Stem cell transplantation ; Stem Cells ; Transfusions. Complications. Transfusion reactions. 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We identify issues that cannot be addressed by conventional analysis of clinical trials and ask whether it is possible to develop a refined analysis to conclude about the outcome of individual patients given clinical trial results. To accomplish this, we propose an interdisciplinary approach based on mathematical modeling. We devise and calibrate a mathematical model of short-term reconstitution and simulate treatment of large patient groups with random interindividual variation. Relating model simulations to clinical data allows quantifying the effect of transplant size on reconstitution time in the terms of patient populations and individual patients. The model confirms the existence of lower bounds on cell dose necessary for secure and efficient reconstitution but suggests that for some patient subpopulations higher thresholds might be appropriate. Simulations demonstrate that relative time gain because of increased cell dose is an ‘interpersonally stable’ parameter, in other words that slowly engrafting patients profit more from transplant enlargements than average cases. We propose a simple mathematical formula to approximate the effect of changes of transplant size on reconstitution time.</description><subject>631/114/2397</subject><subject>631/250/1904</subject><subject>631/61/51/1844</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Algorithms</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Antigens, CD34 - metabolism</subject><subject>Biological and medical sciences</subject><subject>Bone marrow</subject><subject>Bone marrow transplantation</subject><subject>Bone marrow, stem cells transplantation. Graft versus host reaction</subject><subject>Cell Biology</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Clinical trials</subject><subject>Clinical Trials as Topic</subject><subject>Computer Simulation</subject><subject>Cytokines - metabolism</subject><subject>Hematology</subject><subject>Hematopoietic Stem Cell Transplantation - methods</subject><subject>Hematopoietic stem cells</subject><subject>Humans</subject><subject>Infant</subject><subject>Internal Medicine</subject><subject>Mathematical models</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Medicine, Experimental</subject><subject>Middle Aged</subject><subject>Models, Theoretical</subject><subject>Neutrophils - cytology</subject><subject>original-article</subject><subject>Public Health</subject><subject>Reproducibility of Results</subject><subject>Stem cell transplantation</subject><subject>Stem Cells</subject><subject>Transfusions. 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Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Antigens, CD34 - metabolism</topic><topic>Biological and medical sciences</topic><topic>Bone marrow</topic><topic>Bone marrow transplantation</topic><topic>Bone marrow, stem cells transplantation. Graft versus host reaction</topic><topic>Cell Biology</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Clinical trials</topic><topic>Clinical Trials as Topic</topic><topic>Computer Simulation</topic><topic>Cytokines - metabolism</topic><topic>Hematology</topic><topic>Hematopoietic Stem Cell Transplantation - methods</topic><topic>Hematopoietic stem cells</topic><topic>Humans</topic><topic>Infant</topic><topic>Internal Medicine</topic><topic>Mathematical models</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Medicine, Experimental</topic><topic>Middle Aged</topic><topic>Models, Theoretical</topic><topic>Neutrophils - cytology</topic><topic>original-article</topic><topic>Public Health</topic><topic>Reproducibility of Results</topic><topic>Stem cell transplantation</topic><topic>Stem Cells</topic><topic>Transfusions. Complications. Transfusion reactions. 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We identify issues that cannot be addressed by conventional analysis of clinical trials and ask whether it is possible to develop a refined analysis to conclude about the outcome of individual patients given clinical trial results. To accomplish this, we propose an interdisciplinary approach based on mathematical modeling. We devise and calibrate a mathematical model of short-term reconstitution and simulate treatment of large patient groups with random interindividual variation. Relating model simulations to clinical data allows quantifying the effect of transplant size on reconstitution time in the terms of patient populations and individual patients. The model confirms the existence of lower bounds on cell dose necessary for secure and efficient reconstitution but suggests that for some patient subpopulations higher thresholds might be appropriate. Simulations demonstrate that relative time gain because of increased cell dose is an ‘interpersonally stable’ parameter, in other words that slowly engrafting patients profit more from transplant enlargements than average cases. We propose a simple mathematical formula to approximate the effect of changes of transplant size on reconstitution time.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>24056742</pmid><doi>10.1038/bmt.2013.138</doi><tpages>8</tpages></addata></record> |
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| identifier | ISSN: 0268-3369 |
| ispartof | Bone marrow transplantation (Basingstoke), 2014-01, Vol.49 (1), p.30-37 |
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| language | eng |
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| subjects | 631/114/2397 631/250/1904 631/61/51/1844 Adolescent Adult Aged Algorithms Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Antigens, CD34 - metabolism Biological and medical sciences Bone marrow Bone marrow transplantation Bone marrow, stem cells transplantation. Graft versus host reaction Cell Biology Child Child, Preschool Clinical trials Clinical Trials as Topic Computer Simulation Cytokines - metabolism Hematology Hematopoietic Stem Cell Transplantation - methods Hematopoietic stem cells Humans Infant Internal Medicine Mathematical models Medical research Medical sciences Medicine Medicine & Public Health Medicine, Experimental Middle Aged Models, Theoretical Neutrophils - cytology original-article Public Health Reproducibility of Results Stem cell transplantation Stem Cells Transfusions. Complications. Transfusion reactions. Cell and gene therapy Transplantation Transplantation Conditioning - methods Young Adult |
| title | The impact of CD34+ cell dose on engraftment after SCTs: personalized estimates based on mathematical modeling |
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