MIXED HEMATOPOIETIC CHIMERISM AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION - THE IMPACT OF QUANTITATIVE PCR ANALYSIS FOR PREDICTION OF RELAPSE AND GRAFT-REJECTION IN CHILDREN

It still remains unclear whether patients with mixed hematopoietic chi merism (MC) after allogeneic bone marrow transplantation (allo-BMT) ha ve an increased risk of developing relapse or graft failure, To addres s this question, we monitored the individual dynamics of chimerism aft er allo-BMT in pediatric patients within a prospective case control st udy, The individual ratio of donor to recipient peripheral white cells was determined by quantification of genomic variable number of tandem repeats (VNTRs) with a polymerase chain reaction (PCR) approach, With in the study period from 1 January 1994 until 1 July 1996 we investiga ted 50 sequences of 46 pediatric patients after allo-BMT (32 with mali gnant, 18 with nonmalignant diseases), We found complete chimerism (CC ) in 34/50 cases, MC in 12/50 follow-ups and 4/50 patients revealed au tologous recovery (AC), Eight of 12 patients with MC showed increasing autologous patterns and subsequently relapsed or rejected their graft , 3/12 showed decreasing amounts of recipient DNA and turned to CC upo n further follow-up, One patient of 12 who had severe combined immunod eficiency (SCID), attained engraftment with a stable MC pattern, Three patients of 34 with CC relapsed lacking a transitional MC interval, H owever, the time span between last CC confirmation and relapse in each of these three patients was 6 months or longer, We suggest that these patients also developed a stage of transitional MC but that the criti cal timepoint of molecular confirmation by PCR was missed as time inte rvals in the individual follow-up of these three patients were too lon g (greater than or equal to 6 months), In summary, the results demonst rate that the individual risk of developing relapse or graft failure i s significantly enhanced in the MC situation (P < 0.0005), Therefore t he quantitative analysis of MC at short time intervals might be of gre at value to identify high risk patients which will have a significantl y enhanced risk for relapse or graft rejection.