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Engraftment and chimerism, particularly of T- and B-cells, in children undergoing allogeneic bone marrow
J Winiarski1, J Mattsson, A Gustafsson
1Department of Pediatrics, Karolinska Institute, Huddinge University Hospital, Sweden.
Insights
Chimerism analysis using PCR helps monitor bone marrow transplant patients for complications. This technique is crucial for detecting graft failure, relapse, and secondary cancers in pediatric cases.
Area of Science:
- Hematology
- Immunology
- Genetics
Background:
- Pediatric bone marrow transplantation (BMT) now frequently involves mismatched or unrelated donors.
- This shift necessitates enhanced monitoring for complications like graft failure, relapse, and secondary cancers.
Observation:
- A polymerase chain-reaction (PCR) technique was adapted to analyze DNA fragment length polymorphisms for chimerism.
- Immunomagnetically isolated leukocyte populations were used to improve precision in selected cases.
- Seventeen pediatric BMT patients were prospectively followed.
Findings:
- Five patients experienced chimerism-related clinical issues, including graft failure, graft-versus-host disease, mixed chimerism with relapse, persistent recipient T-cells, and fatal donor cell lymphoma.
- Twelve children achieved stable full chimerism or low-grade mixed chimerism and remained disease-free.
- Chimerism analysis provided critical insights into patient outcomes.
Implications:
- Chimerism analysis, especially of leukocyte subsets, is vital for managing complex BMT cases.
- It aids therapeutic decisions in transplants with unrelated/mismatched donors, graft manipulation, adoptive immunotherapy, and immunodeficiency.
- This monitoring is essential for improving outcomes in high-risk pediatric BMT.
Abstract:
The spectrum of pediatric bone marrow transplantation has changed in recent years. Mismatched and unrelated donor transplants are common, demanding an increased vigilance to detect incipient graft failure, secondary lymphoma as well as relapse and other problems, which now are potentially treatable. To diagnose these complications it may be important to know whether blood and marrow cells are of recipient or donor origin. To evaluate the role of mixed donor-recipient chimerism in relation to clinical problems we adapted a polymerase chain-reaction technique, using fluorescent primers analyzing DNA fragment length polymorphisms, to follow prospectively 17 bone marrow grafted children. To increase the precision of chimerism analysis, immunomagnetically isolated leukocyte populations were assayed in selected cases. Five patients encountered clinical problems related to chimerism. One infant with adenosine deaminase deficiency failed to engraft stem cells, yet succumbed to graft-versus-host disease, mediated by mature donor T-cells. Three children developed significant mixed chimerism. One of these three patients died in relapse of leukemia, while the two other patients who had received T-cell depleted grafts had persistent recipient T-cells, in spite of engraftment. After 5 months, these were displaced by donor T-cells in one of the patients. In the fifth patient, also after T-cell depleted BMT, a fatal donor cell lymphoma occurred. Twelve children had stable full chimerism or in one case a low grade mixed chimerism and remain disease-free throughout follow up (median 9 months). In conclusion, the analysis of chimerism, particularly of separated leukocyte populations, offers an almost indispensable insight and a basis for therapeutic decisions in complicated situations such as grafting involving unrelated or mismatched donors, graft manipulation, adoptive immunotherapy and in immunodeficiency patients.