Incidence of mixed chimaerism and clinical outcome in 101 patients after myeloablative conditioning regimens and allogeneic stem cell transplantation

Abstract

Summary. In the light of reduced intensity conditioning regimens for allogeneic transplantation, monitoring of donor cell engraftment acquires new relevance. We analysed the clinical significance of haematopoietic chimaerism as a parameter of patient outcome and detection of relapse for early intervention by donor lymphocyte infusion (DLI) after allogeneic transplantation. Between July 1994 and March 1999, 101 adult patients with malignant disease were evaluated. Median follow-up was 15 months (range 0´7±56´5) after transplantation. Patients received busulphan-containing (n 82) or total body irradiation (TBI)-containing (n 19) regimens. Fifteen out of 98 (15%) patients with predictive chimaerism analyses relapsed, 5 out of 20 (25%) with mixed chimaerism (MC) and 10 out of 78 (13%) with complete donor chimaerism (CC) before apparent relapse. Seven patients received donor lymphocyte infusions (DLI) as relapse therapy with conversion from MC to CC in all three patients with successful DLI. Our data stress the importance of chimaerism monitoring after allogeneic transplantation and demonstrate the more frequent occurrence of disease relapse in patients showing MC, rather than CC, after transplantation. Moreover, the assessment of chimaerism has been shown to be a valuable tool in monitoring the efficiency of donor lymphocyte infusions for relapse.

Induction of graft versus malignancy effect after unrelated allogeneic PBSCT using donor lymphocyte infusions derived from frozen aliquots of the original graft

“…1,24 This furthermore stresses the importance of tight monitoring of minimal residual disease, chimerism or molecular relapse and subsequent early DLI. [25][26][27] Positive prognostic factors for better survival were development of cGvHD after the initial PBSCT and time from PBSCT. Preexisting cGVHD possibly reflects a more pronounced GvL effect in those patients.…”

Chimerism analysis within 6 months of allogeneic stem cell transplantation predicts relapse in acute myeloid leukemia

“…Table 5 shows an overview of previous reports on the association between MC and relapse in adult patients with AML. [16][17][18][19][20][21][22] It is important to note that the two studies that did not find a relation between MC and relapse did not distinguish between stable and increasing MC.…”

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

“…[2][3][4][5][6][7][8] The predictive value of MC in an individual patient for either graft rejection or relapse is controversial. [9][10][11][12] Some studies indicate that MC is associated with these complications, [13][14][15][16][17][18][19][20][21][22][23] while others do not corroborate this finding. 24,25 The lack of association of MC with graft rejection and relapse in some studies might be because of the fact that chimerism was not analysed in the cell subsets responsible for these complications.…”