Article

Early recipient chimerism testing in the T- and NK-cell lineages for risk assessment of graft rejection in pediatric patients undergoing allogeneic stem cell transplantation.

St Anna Children's Hospital, Vienna, Austria.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K (Impact Factor: 9.38). 09/2011; 26(3):509-19. DOI: 10.1038/leu.2011.244
Source: PubMed

ABSTRACT Timely diagnosis of impending graft rejection is crucial for effective therapeutic intervention after allogeneic hematopoietic stem cell transplantation (SCT). We have investigated the predictive potential of early leukocyte subset-specific chimerism for graft loss in children undergoing SCT. In total, 192 pediatric patients transplanted for the treatment of malignant and non-malignant diseases after reduced-intensity or myeloablative conditioning were investigated. Surveillance of lineage-specific chimerism was initiated upon first appearance of leukocyte counts amenable to cell sorting. Graft rejection occurred in 23 patients between 24 and 492 days post-transplant (median 63 days). The first chimerism analysis of T and NK cells performed at a median of 20 days after SCT identified three different risk groups that were independent from the conditioning regimen: recipient chimerism (RC) levels in T cells below 50% indicated a very low risk of rejection (1.4%), whereas high levels of RC (>90%) both in T and NK cells heralded graft loss in the majority of patients (90%) despite therapeutic interventions. RC >50% in T cells and ≤90% in NK cells defined an intermediate-risk group in which timely immunotherapy frequently prevented rejection. Early assessment of T- and NK-cell chimerism can therefore be instrumental in the risk assessment and therapeutic management of imminent graft rejection.

0 Followers
 · 
193 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chimerism dynamics in bone marrow, peripheral blood (PB), and T lymphocytes (TLs) has been associated with the development of various complications after allogeneic stem-cell transplantation (allo-SCT). In the present study, the usefulness of chimerism monitoring in CD25(+)-activated leukocytes (ALs), together with that in bone marrow, PB, and TLs, for the anticipation of complications after allo-SCT, has been analyzed in 68 patients. In ALs, we observed a slower dynamics toward complete chimerism (CC) than in PB (p = 0.042), while no significant differences were found between TLs and PB (p = 0.12). Complete chimerism achievement in AL at day +30 has shown to be an independent risk factor for the development of grade II-IV acute graft-versus-host disease (aGvHD; hazard ratio [95% confidence interval]: 11.9 [1.5-91.7]; p = 0.017). Moreover, among patients achieving CC in TLs and ALs at different time-points after SCT (n = 17/68), the incidence of grade II-IV aGvHD was significantly higher in patients who achieved CC earlier in ALs (5/5) than in those who achieved CC earlier in TLs (1/11; p = 0.001). Therefore, achievement of early complete donor chimerism in CD25(+) ALs is a strong predictor for the development of aGvHD. Prospective analysis of chimerism in ALs could improve the post-SCT management of immunosuppressive therapy in transplanted patients. Copyright © 2014 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.
    Experimental Hematology 10/2014; 43(1). DOI:10.1016/j.exphem.2014.09.003 · 2.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Little is known regarding the chimerism status after reduced-intensity conditioning transplantation when bone marrow is used as a stem cell source. We prospectively analyzed lineage-specific chimerism and retrospectively evaluated clinical outcomes in 80 adult patients who underwent unrelated donor bone marrow transplantation (URBMT) with fludarabine plus melphalan (FM) as the conditioning regimen. Mixed donor chimerism (MDC) was seen in 43 and 10 % of patients at days 14 and 28, respectively. Melphalan at ≤130 mg/m(2) was associated with an increased incidence of MDC at day 28 (P = 0.03). Patients with MDC at day 14 showed a marginally increased risk of primary graft failure and a marginally decreased risk of graft-versus-host disease. In multivariate analysis, MDC at day 14 was associated with higher overall mortality (hazard ratio (HR) = 2.1; 95 % confidence interval (CI), 1.1-4.2; P = 0.04) and relapse rate (HR = 3.0; 95 % CI, 1.2-7.5; P = 0.02), but not with non-relapse mortality (HR = 1.8; 95 % CI, 0.70-4.6; P = 0.23). Thus, the FM regimen yields prompt complete donor chimerism after URBMT, but the melphalan dose significantly impacts the kinetics of chimerism. Chimerism status evaluation at day 14 may be instrumental in predicting relapse after URBMT with the FM regimen.
    Annals of Hematology 02/2015; DOI:10.1007/s00277-015-2312-4 · 2.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mixed donor chimerism is increasingly common in the pediatric HSCT setting due to the increased use of reduced intensity preparative regimens for non-malignant diseases. Donor lymphocyte infusion (DLI) is potentially useful in the treatment of mixed donor chimerism but there is little data available on the use of DLI in this setting. We conducted a retrospective review of 27 pediatric patients who received DLI for mixed donor chimerism between January 2006 and December 2010 after receiving a preparative regimen of alemtuzumab, fludarabine, and melphalan. Twenty one patients (78%) are alive at a median of 35 months post transplant. Seven patients (26%) have sustained full donor chimerism following DLI only at a median of 35 months post HSCT. Nine patients (33%) continue with mixed donor chimerism (median 38%, range 18-70%) at a median of 37 months following DLI only. Five patients underwent unconditioned stem cell boosts or second conditioned transplants after no improvement in donor chimerism was seen following DLI. Donor source appeared to contribute to outcomes following DLI; patients with mismatched unrelated donors had earlier first decline in chimerism and timing of first DLI, a higher response rate to DLI, and an increased rate of GVHD. There was no response to DLI in patients with matched sibling donors. Ten patients, all with improvement in chimerism following DLI, developed acute GVHD following DLI, with three having grade III GVHD. Three patients developed chronic GVHD following DLI. This data illustrate the potential efficacy of DLI in the treatment of mixed donor chimerism following a reduced intensity preparative regimen.
    Biology of Blood and Marrow Transplantation 10/2014; 21(2). DOI:10.1016/j.bbmt.2014.10.010 · 3.35 Impact Factor

Full-text (2 Sources)

Download
17 Downloads
Available from
Jun 16, 2014