HSCT Status Detection Using Polymorphic Nucleic Acid Markers
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Solution Overview
Problem
Current methods for monitoring hematopoietic stem cell transplantation (HSCT) status are costly, resource-intensive, and often detect graft failure too late, as they rely on functional lymphocyte populations or cell-free DNA analysis, which is complicated by mixed nucleic acid sources and interference from recipient DNA in conditions like cancer or graft-versus-host disease.
Innovation Solution
A method involving the measurement of recipient-specific and donor-specific nucleic acids in HSCT recipients, using polymorphic nucleic acid targets and high-throughput sequencing or digital PCR to determine transplant status by analyzing genomic DNA from peripheral white blood cells, allowing for early detection of graft failure or engraftment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If functional lymphocyte population detection is used to monitor HSCT status, then transplantation status can be determined, but the detection is made too late when significant injury has already occurred and the method is technically challenging and resource demanding
Solution Approach 1:
The patent applies preliminary action by detecting donor chimerism at early time points after transplantation (e.g., day +10 to +30) using polymorphic nucleic acid markers before graft failure occurs. This allows prediction of engraftment status before clinical symptoms manifest, enabling preventive intervention rather than reactive treatment after significant injury has occurred.
2Quantity of substance
If cell-free DNA analysis is used to determine HSCT status, then nucleic acid quantification can be performed, but the mixed nucleic acid sources from multiple origins and interference from recipient DNA in conditions like cancer or graft-versus-host disease render it challenging to conclusively correlate donor fraction to engraftment status
Solution Approach 1:
The patent extracts and analyzes only polymorphic nucleic acid markers that differ between donor and recipient, isolating the informative signals from the mixed nucleic acid background. By focusing on specific polymorphic loci rather than total cell-free DNA, the method eliminates interference from recipient DNA and other mixed sources, enabling accurate donor fraction determination even in complex clinical scenarios.
Solution Approach 2:
The patent applies local quality by examining specific polymorphic regions of nucleic acids rather than analyzing bulk DNA. This localized approach to specific genetic markers with known polymorphisms between donor and recipient allows precise differentiation of donor-derived nucleic acids from recipient-derived nucleic acids, improving measurement precision in the presence of mixed sources.
3Measurement precision
If current HSCT monitoring methods are used, then transplantation status can be assessed, but the methods are costly and resource-intensive
Solution Approach 1:
The patent employs disposable, standardized polymorphic nucleic acid marker panels that can be rapidly amplified and detected using high-throughput sequencing or digital PCR. These standardized assays replace complex, expensive functional lymphocyte population analyses with more economical molecular genetic tests that use readily available reagents and can be processed efficiently in high-volume settings, reducing both direct costs and resource requirements.
Data Source
AI summary
This application provides methods and systems for determining transplant status. In some embodiments, the method comprises obtaining a biological sample from hematopoietic stem cell transplant (HSCT) recipient; measuring the amount of one or more identified recipient-specific nucleic acids or donor-specific nucleic acids in the sample; and (c) determining transplant status by monitoring the amount of the one or more identified recipient-specific nucleic acids or donor-specific nucleic acids after transplantation. In some approaches, the one or more recipient-specific or the donor-specific nucleic acids are identified based on the amount of one or more polymorphic nucleic acid targets, which can be used to determine the transplant status. Optionally, the biological sample is blood or bone marrow. Optionally the nucleic acid is genomic DNA.