Recipient origin fetal microchimerism in development of acute GVHD after haploidentical BMT

Abstract

Haploidentical transplantation of hematopoietic stem cells (haplo-HSCT) is a feasible therapeutic approach in patients lacking an HLA-identical donor. Currently, there exist some data concerning associations between maternal microchimerism levels (detection of maternal cells in recipient’s blood) and increased risk for GVHD development. Meanwhile, the effects of microchimerism upon GVHD probability are still controversial. The aim of our study was to adapt a technique for quantitative evaluation of fetal (recipient-cell) and mathernal (donor-cell) microchimerism and investigation of its effects upon actual risk of common complications after HSCT. Determination of microchimerism was carried out by real-time alle-specific polymerase chain reaction (AS RQ-PCR). The analytic panel included 20 InDel markers located at different chromosomes. Evaluation of PCR sensitivity was carried out using DNA mixtures from several established cell lines at serial dilutions. The samples from 20 donor-recipient pairs were analyzed. The patients’ age ranged from 2 to 27 years. The sensitivity thresholds for the InDel-based test panel ranged from 10ˆ- 4 to 10ˆ-5. We have found out that detection of fetal microchimerism in the donor organism is associated with lower risk, or lower degree of acute GVHD (p=0.01). Moreover, we observed a trend to higher timeframe for transplant engraftment, and lower probability of full donor chimerism achievement, if the donor exhibited fetal microchimerism (p=0.12). The patients in our setting transplanted from donors with detectable fetal microchimerism had a tendency to a higher overall survival (p=0.14). Hovewer, we did not reveal any significant association between microchimerism levels (fetal and maternal), and higher probability of chronic GVHD development, as well as any differences in other posttransplant complica- tions for recipients with maternal microchimerism. Evaluation of fetal microchimerism may be considered a useful and informative approach to selection of potential donors, or a method of GVHD prediction in haploidentical HSCT.