Follow-up of chimerism, including T- and B-lymphocytes and granulocytes in children more than one year after allogeneic bone marrow transplantation.
In bone-marrow-transplanted children, early detection of graft failure, relapse, and other potentially treatable problems is facilitated by the use of polymerase chain reaction (PCR) assays that monitor whether blood and marrow cells are of recipient or donor origin. Presence of mixed donor-recipient chimerism (MC) within the first year after BMT frequently correlates with clinical problems. To study if MC detected one year or more post-BMT was also often associated with clinical problems, the chimeric status in 33 children surviving 1-11 yr (median: 2 yr) after BMT was investigated. A PCR with a sensitivity of 1-2%, using fluorescent primers analyzing DNA fragment length polymorphisms, was applied. T- and B-cells and granulocytes were immunomagnetically isolated and tested separately for all patients. Of the 33 patients, of whom 21 had received pretreatment including total body irradiation (TBI), 27 (82%) exhibited full donor chimerism. Six children (18%), four of whom had received pretreatment without TBI, had MC. In three of these children, all with aplastic anemia, isolated T-cell MC had not posed apparent clinical problems. In two patients, both with MC including B-cells, immune hemolytic anemia was observed. A sixth patient with AML presented with MC and relapse. In two of the six children MC was detected only by cell subset analysis. In conclusion, analysis of MC in leukocyte subsets is more informative than analysis of whole blood only and may reveal clinically important variations in the origin of different cell populations. The prevalence of MC is lower after the first year post-BMT, and when present is less often associated with clinical problems.
Department of Pediatrics, Karolinska Institutet, Huddinge University Hospital, Sweden.
J
J
Winiarski
A
A
Gustafsson
D
D
Wester
T
T
Dalianis
D000293:Adolescent; D001402:B-Lymphocytes; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes; D018183:Transplantation Chimera