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Serial quantification of lymphoid and myeloid mixed chimerism using multiplex PCR amplification of short tandem repeat-markers predicts graft rejection and relapse, respectively, after allogeneic transplantation of CD34+ selected cells from peripheral blood

Abstract

We used multiplex amplification of nine microsatellite sequences (PCR-STR) to analyse chimerism in pure populations of T cells and neutrophils from peripheral blood from 40 patients submitted to an allogeneic transplant, 22 having received a T-cell depleted (TCD) peripheral blood graft by means of CD34+ selection (allo-PBT/CD34+), and 18, an unmodified graft (allo-SCT; 13 allogeneic bone marrow transplants and five allo-PBT). T-cell mixed chimerism (TcMC) was observed in 16 of the 22 (72.3%) patients receiving an allo-PBT/CD34+, but in only one of the 18 (5.5%) patients receiving an allo-SCT (P=0.0001). TcMC was transient (n=6), stable (n=7), and associated with poor haematopoietic engraftment (n=4). All patients with TcMC who developed graft failure had more than 30% of host T cells. Myeloid MC (MyMC) was observed in four (19%) allo-PBT/CD34+ patients and in three (17%) allo-SCT patients (P=NS). Five out of seven (71%) patients with MyMC relapsed, all of them diagnosed with myeloid malignancies, as compared with two of the 20 (10%) patients with complete donor chimerism (P<0.0001). In conclusion, TcMC appears in a significant number of allo-PBT/CD34+ patients and may be associated with poor engraftment when the percentage of host T cells is >30%; likewise, MyMC appears in a small percentage of recipients of both allo-PBT/CD34+ and allo-SCT patients, and is associated with leukaemia relapse in myeloid malignancies.

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Acknowledgements

This work was supported in part by Grants FIJC-01/P-CR and FIJC-01/P-EM from the José Carreras International Foundation.

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Fernández-Avilés, F., Urbano-Ispizua, A., Aymerich, M. et al. Serial quantification of lymphoid and myeloid mixed chimerism using multiplex PCR amplification of short tandem repeat-markers predicts graft rejection and relapse, respectively, after allogeneic transplantation of CD34+ selected cells from peripheral blood. Leukemia 17, 613–620 (2003). https://doi.org/10.1038/sj.leu.2402854

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