title: Mixed hematopoietic chimerism after allogeneic bone marrow transplantation: the impact of quantitative PCR analysis for prediction of relapse and graft rejection in children.
abstract: It still remains unclear whether patients with mixed hematopoietic chimerism (MC) after allogeneic bone marrow transplantation (allo-BMT) have an increased risk of developing relapse or graft failure. To address this question, we monitored the individual dynamics of chimerism after allo-BMT in pediatric patients within a prospective case control study. 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. Within the study period from 1 January 1994 until 1 July 1996 we investigated 50 sequences of 46 pediatric patients after allo-BMT (32 with malignant, 18 with nonmalignant diseases). We found complete chimerism (CC) in 34/50 cases, MC in 12/50 follow-ups and 4/50 patients revealed autologous recovery (AC). Eight of 12 patients with MC showed increasing autologous patterns and subsequently relapsed or rejected their graft, 3/12 decreasing amounts of recipient DNA and turned to CC upon further follow-up. One patient of 12 who had severe combined immunodeficiency (SCID), attained engraftment with a stable MC pattern. Three patients of 34 with CC relapsed lacking a transitional MC interval. However, 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 critical timepoint of molecular confirmation by PCR was missed as time intervals in the individual follow-up of these three patients were too long (> or = 6 months). In summary, the results demonstrate that the individual risk of developing relapse or graft failure is significantly enhanced in the MC situation (P < 0.0005). Therefore the quantitative analysis of MC at short time intervals might be of great value to identify high risk patients which will have a significantly/enhanced risk for relapse or graft rejection.
authors.affiliation: University Children's Hospital, Department of Pediatric Hematology and Oncology, Tübingen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Bader
authors.forename: W
authors.initials: W
authors.lastname: Hölle
authors.forename: T
authors.initials: T
authors.lastname: Klingebiel
authors.forename: R
authors.initials: R
authors.lastname: Handgretinger
authors.forename: N
authors.initials: N
authors.lastname: Benda
authors.forename: P G
authors.initials: PG
authors.lastname: Schlegel
authors.forename: D
authors.initials: D
authors.lastname: Niethammer
authors.forename: J
authors.initials: J
authors.lastname: Beck
mesh_terms: D000293:Adolescent; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D006084:Graft Rejection / Q000235:genetics; D019337:Hematologic Neoplasms / Q000473:pathology / Q000628:therapy*; D006410:Hematopoiesis / Q000235:genetics*; D006801:Humans; D007223:Infant; D016133:Polymerase Chain Reaction / Q000379:methods; D011237:Predictive Value of Tests; D012008:Recurrence; D018183:Transplantation Chimera / Q000235:genetics*