Characterization of lineage‐specific chimaerism in patients with acute leukaemia and myelodysplastic syndrome after allogeneic stem cell transplantation before and after relapse

Recently, we have shown that patients with acute leukaemias and myelodysplastic syndromes (MDS), who showed increasing mixed chimaerism (MC) upon serial PCR analysis after transplant, have a significantly increased risk of relapse. To determine whether the increasing MC in these patients is caused b...

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Bibliographic Details
Published in:British journal of haematology 2000-03, Vol.108 (4), p.761-768
Main Authors: Bader, P., Stoll, K., Huber, S., Geiselhart, A., Handgretinger, R., Niemeyer, C., Einsele, H., Schlegel, P. G., Niethammer, D., Beck, J., Klingebiel, T.
Format: Article
Language:English
Subjects:
acute leukaemia
Adolescent
Adult
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Biological and medical sciences
Bone marrow, stem cells transplantation. Graft versus host reaction
Child
Child, Preschool
Graft vs Host Disease - blood
haematopoietic chimaerism
Hematology
Hematopoietic Stem Cell Transplantation
Humans
Infant
Leukemia, Myeloid, Acute - blood
Leukemia, Myeloid, Acute - therapy
Medical sciences
Middle Aged
Myelodysplastic Syndromes - blood
Myelodysplastic Syndromes - therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood
Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy
Recurrence
relapse
stem cell transplantation
Time Factors
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
Transplantation Chimera
Transplantation, Homologous
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Summary:Recently, we have shown that patients with acute leukaemias and myelodysplastic syndromes (MDS), who showed increasing mixed chimaerism (MC) upon serial PCR analysis after transplant, have a significantly increased risk of relapse. To determine whether the increasing MC in these patients is caused by the reappearance of normal recipient haematopoiesis or by the reoccurrence of malignant cells, we purified different leucocyte subpopulations and analysed these subfractions with regard to their donor–recipient ratio by a PCR‐based method for the analysis of minisatellite DNA regions. In 14 patients [eight acute lymphoblastic leukaemia (ALL), three acute myelogenous leukaemia (AML) and three MDS] subfractions were analysed when increasing MC was first noted upon serial analysis of the peripheral blood. In seven of these 14 patients (four ALL, two AML and one MDS), subfractions were characterized at the time of frank haematological relapse. In all 14 patients investigated with increasing MC, recipient cells were detected in different mononuclear cell subpopulations. In patients characterized during frank relapse, two distinct distribution patterns were found. Patients who relapsed before day +300 (one ALL, two AML and one MDS) showed recipient‐derived (normal) cells in addition to blast populations in different mononuclear subsets as well as granulocytes. In patients with acute leukaemias who relapsed after day +300 (two ALL and one AML), only leukaemic cells were found that were of recipient origin, whereas all other haematopoietic cell lines were donor derived. These data show that persistent MC in the early post‐transplant period is caused predominantly by normal recipient haematopoietic cells. This finding further supports the hypothesis that a state of mixed haematopoietic chimaerism may reduce the clinical graft‐versus‐leukaemia (GVL) effect of alloreactive donor‐derived effector cells in patients with acute leukaemias and MDS, and thus facilitate the proliferation of residual malignant cells that may have survived the preparative regimen.
ISSN:0007-1048
1365-2141
DOI:10.1046/j.1365-2141.2000.01927.x