The role of the H&I laboratory in post stem cell transplant monitoring is to provide clinicians with accurate information of the engraftment status by quantitatively determining the proportion of donor and recipient derived cells in the patient post transplant. Most H&I laboratories use Short Tandem Repeats (STR’s) for this. STR’s are short sequences of DNA, distributed throughout the genome which are repeated in tandem a variable number of times. The number of repeats of different STR markers varies between individuals, from 4 to 50 repeats for some STRs, giving a highly polymorphic system that can be used to uniquely identify donor derived DNA from patient derived DNA. With the exception of monozygotic twins, careful selection of a number of STR markers will enable most patients derived DNA to be distinguished from donor derived DNA.
Post stem cell transplant chimerism results are typically reported as % donor chimerism. A 100% donor chimera implies complete engraftment. A 0% donor chimerism implies no donor engraftment with all other percentages reported as mixed chimerism showing the proportion of donor engraftment. A longitudinal study of donor engraftment is of more value than a single static result and the H&I laboratory would typically test at agreed intervals and report a history of the chimeric status of the patient since transplant rather than a single test report. The relative changes in magnitude of the donor chimerism provide key information which help clinicians to intervene and to monitor the patients’ response to such intervention. Intervention options include changes in immunosuppression regimes and donor lymphocyte infusion.
Longitudinal STR chimerism analysis is particularly useful in reduced intensity conditioning (RIC) regimes where initial mixed chimerism post transplant is relatively common. The frequency of testing is agreed between the H&I laboratory and the transplant centre. For myeloablative regimens, this is typically weekly in the first month post transplant followed by monthly testing. For RIC regimes this is typically monthly.
While STR analysis can be performed on whole blood, many H&I laboratories will offer lineage specific STR analysis, separating T and B cells from myeloid cells. This approach increases the sensitivity of the technique and has proved useful in some cases of mixed chimerism, where the initial myeloid mixed chimerism may dominate and mask clinically significant changes in other cell subsets.
The use of STR for chimerism analysis has also proved useful in the case of double cord transplants where it is possible to see a mixed chimera consisting of patient and one or both cords early in the post transplant period before one cord eventually expands to 100% present in the patient.
Stable mixed chimerism post transplant does not necessarily indicate a need to treat particularly in diseases such as Aplastic Anaemia (AA) and other non malignant conditions especially where RIC regimes have been used. STR results showing increasing donor proportion is good whilst STR results showing increasingly recipient proportion may indicate relapse or graft rejection and may indicate a need to treat. As mentioned, treatment options include a change in immunosuppression and/or Donor Lymphocyte Infusion (DLI).
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