From the Guidelines
Monitoring of myeloid chimerism is crucial after allogeneic hematopoietic stem cell transplantation (HSCT) to assess transplant success and predict outcomes, with declining donor chimerism or mixed chimerism early after HSCT considered signs of imminent relapse. Myeloid chimerism refers to the presence of donor-derived myeloid cells in a recipient following HSCT. The ideal goal is to achieve complete donor chimerism, where 95-100% of myeloid cells are of donor origin. For patients with mixed chimerism (both donor and recipient cells present), intervention may be necessary, typically through immunosuppression reduction or donor lymphocyte infusions (DLIs) 1.
Importance of Chimerism Monitoring
- Chimerism testing should be performed at regular intervals post-transplant to monitor for signs of relapse or graft rejection.
- The clinical significance of myeloid chimerism varies by disease, but it's particularly important in myeloid malignancies where decreasing donor chimerism may indicate disease relapse 1.
- Molecular monitoring after HSCT has been performed retrospectively in 36 MDS/myeloproliferative neoplasm patients, showing that patients with detectable mutations after HSCT had a higher incidence of relapse than in patients with undetectable mutations 1.
Chimerism Analysis
- Chimerism analysis uses molecular techniques like short tandem repeat (STR) PCR or next-generation sequencing to distinguish between donor and recipient cells.
- Monitoring of chimerism in sorted CD34 cells has been used as MRD monitoring after HSCT in MDS, providing crucial information for managing post-transplant care and identifying patients at risk for graft rejection or disease recurrence 1.
From the Research
Myeloid Chimerism
- Myeloid chimerism refers to the presence of donor and recipient cells in the myeloid lineage after allogeneic stem cell transplantation 2, 3, 4.
- Monitoring of donor chimerism in the myeloid lineage can detect early relapse following transplantation for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) 2, 4.
- Studies have shown that peripheral blood CD34+ donor chimerism is more predictive of relapse than CD3+ donor chimerism 2.
- The use of lineage-specific chimerism, such as CD34+ chimerism, can improve relapse detection and guide therapy decisions 3, 4.
Detection of Relapse
- Sequential monitoring of chimerism in circulating CD34+ cells can detect relapse in patients after allogeneic stem cell transplantation 4.
- A decrease in donor CD34+ cells can precede clinical diagnosis of relapse by 12-97 days (median 52 days) 4.
- Treatment, such as reduction of immunosuppression, donor lymphocyte infusion, or tyrosine kinase inhibitors, can increase donor-derived CD34+ cells and clear malignant cells 4.
Chimerism Testing
- Chimerism testing can assess the relative percentage of donor to recipient hematopoietic cells based on genetic differences 3.
- Various laboratory techniques can be used to compute donor chimerism percentage, including polymerase chain reaction-based amplification of polymorphic short tandem repeat regions 5.
- External factors, such as the type of conditioning regimen, can influence the relative value of donor to recipient chimerism 5.
Graft-Versus-Host Disease
- Graft-versus-host disease (GvHD) remains a significant complication after allogeneic hematopoietic stem cell transplantation 6.
- Longitudinal monitoring of chimerism in CD3+ T-cell subsets can predict the development of GvHD among patients undergoing HSCT 6.
- The risk of acute GvHD correlates with the CD34+ cell dose, while the risk of extensive chronic GvHD is associated with high CD3+ donor chimerism on day 30 6.