Lineage-specific chimerism analysis in nucleated cells, T cells and natural killer cells after myeloablative allogeneic hematopoietic stem cell transplantation

Abstract

BackgroundChimerism analysis is an important tool for assessing the origin of hematopoietic cells after allogeneic stem cell transplantation (allo-SCT) and can be used to detect impending graft rejection and the recurrence of underlying malignant or nonmalignant diseases.MethodsThis study included 24 patients who underwent myeloablative allo-SCT. DNA was extracted from nucleated cells (NCs), T cells, and natural killer (NK) cells, and the chimerism status of these cell fractions was determined by STR-PCR performed using an automated fluorescent DNA analyzer.ResultsTwenty-three out of the 24 patients achieved engraftment. Mixed chimerism (MC) in NCs, but not in T cells and NK cells, was significantly correlated with disease relapse. MC in all cell fractions was correlated with mortality. Ten patients (41.6%) developed extensive chronic GVHD. Six patients had MC in T cells, and 3 of them had chronic GVHD. Four patients with MC and relapse received donor lymphocyte infusion (DLI), and among them, 3 had secondary relapse. Further, the chimerism status differed among different cell lineages in 6 patients with myeloid malignancies.ConclusionThe implications of MC in lymphocyte subsets are an important area for future research. Chimerism analysis in lineage-specific cells permits detection of relapse and facilitates the monitoring of therapeutic interventions. These results can provide the basic data for chimerism analysis after myeloablative SCT.

Mixed chimerism in haemoglobinopathies: from risk of graft rejection to immune tolerance

“…Analysis of chimerism in the different cellular compartments is a useful diagnostic tool for monitoring engraftment and consequently for evaluating transplant outcome. Some studies have proposed an association between the persistence of recipient T cells after unmanipulated or T cell‐depleted HCT and an increased risk of recurrent malignancy (46–48). Conversely, in a recent study, Martin et al suggested that low donor T cell chimerism was not associated with a reduced risk of relapse , while Antin et al showed that patients with more‐rapid (i.e.…”

Assessment of lineage-specific chimerism after allogeneic stem cell transplantation

“…Similar data were provided by El-Cheikh et al [13] who found that acute GVHD was predictive of full donor T-cell chimerism after RIC allo-SCT. Early assessment of T-and NK-cell chimerism was proved to be instrumental in the risk assessment and therapeutic management of imminent graft rejection [13][14][15][16]. Detection of predominant host-origin T and NK cells were strongly predictive of graft loss in the majority of patients despite therapeutic interventions [13].…”

Assessment of the purity of isolated cell populations for lineage‐specific chimerism monitoring post haematopoietic stem cell transplantation

“…Recent studies have indicated that chimerism levels in different cell subsets may affect clinical outcome (8)(9)(10)(11)(12)(13)(14)(15). For example, early identification of mixed chimerism in T cells and NK cells has been shown to allow classification of patients into groups with different risk of graft rejection (8), and full donor T-cell chimerism has been shown to precede graft vs tumour effects.…”

“…Lineage‐specific chimerism monitoring is increasingly utilised to specifically detect chimerism in one or more cell subsets, and offers the advantage of identifying mixed chimerism confined to specific lineages which may be undetected in assessment of the whole leukocyte population. Recent studies have indicated that chimerism levels in different cell subsets may affect clinical outcome . For example, early identification of mixed chimerism in T cells and NK cells has been shown to allow classification of patients into groups with different risk of graft rejection , and full donor T‐cell chimerism has been shown to precede graft vs tumour effects.…”