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. 2003 Mar;17(3):613-20. doi: 10.1038/sj.leu.2402854.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD34
  • Bone Marrow Transplantation / methods
  • Bone Marrow Transplantation / standards
  • Female
  • Graft Rejection
  • Humans
  • Leukemia / therapy
  • Leukocytes / cytology*
  • Lymphocyte Depletion
  • Male
  • Middle Aged
  • Myeloid Cells / cytology*
  • Peripheral Blood Stem Cell Transplantation / methods
  • Peripheral Blood Stem Cell Transplantation / standards*
  • Polymerase Chain Reaction / methods*
  • Polymerase Chain Reaction / standards
  • Predictive Value of Tests
  • Prospective Studies
  • Recurrence
  • Tandem Repeat Sequences*
  • Transplantation Chimera*
  • Transplantation, Homologous / methods
  • Transplantation, Homologous / standards

Substances

  • Antigens, CD34