Comparative serial quantitative measurements of chimaerism following unmanipulated allogeneic transplantation of peripheral blood stem cells and bone marrow

Abstract

Summary. Serial samples were collected from 38 patients following allogeneic transplantation using either unmanipulated peripheral blood stem cells (PBSC) (n 18) or bone marrow (BM) (n 20) to assess the incidence of mixed chimaerism using PCR ampli®cation of ®ve VNTR regions. After ampli®cation, products were analysed using the Applied Biosystems ABI PRISM 377 Automated DNA Sequencer and GeneScan software GenoTyper program to determine a quantitative measure of chimaerism. The sensitivity of detection using this method was 0´1%.In the immediate post-transplant period (up to day 30) a signi®cantly lower incidence of mixed chimaerism (MC) occurred in recipients of PBSC compared to BM (P < 0´0005). Between 1 and 6 months there was a signi®cantly lower incidence of low-level MC in patients receiving PBSCT compared to BMT (4/14 v 8/11 respectively, P 0´04) in patients who had not rejected their grafts or relapsed. Similarly, beyond 6 months 0/9 PBSCT patients compared to 4/9 BMT patients showed MC (P 0´02). Beyond day 30 13/33 (39%) patients showed intermittent low-level MC, but this was not predictive for subsequent relapse. A rapidly increasing proportion of recipient haemopoiesis was predictive of graft rejection or relapse. Stable continuous MC without relapse was seen in one patient transplanted with PBSC for severe aplastic anaemia. These results suggest that the incidence of intermittent low-level MC is relatively high in the ®rst 6 months following unmanipulated haemopoietic stem cell transplantation but reduces with time and is signi®cantly lower in recipients of PBSC.

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

“…After a median (range) follow-up of 15 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) Table 1. )…”

“…[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.…”

Campath-1G causes rapid depletion of circulating host dendritic cells (DCs) before allogeneic transplantation but does not delay donor DC reconstitution

“…Electrophoresis was for 5 hours at 40 W and 48°C with a GS-500 marker (Applied Biosystems) in each lane. Data were analyzed using Genescan Analysis software and quantitation of percentage of donor chimerism was as described by Miflin et al 30 …”

Prompt initiation of immunotherapy in children with an increasing number of autologous cells after allogeneic HCT can induce complete donor-type chimerism: a report of 14 children

“…Children with an increasing number of host-derived cells (increasing mixed chimerism, inMC) have the highest risk of either graft rejection or relapse. [15][16][17][18] Encouraged by these results we have asked the question whether it would be possible to prevent relapse or rejection in children with an increasing amount of autologous DNA by prompt immunotherapy together with the withdrawal of immunosuppression or DLI.…”