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

Citation
P. Bader et al., Characterization of lineage-specific chimaerism in patients with acute leukaemia and myelodysplastic syndrome after allogeneic stem cell transplantation before and after relapse, BR J HAEM, 108(4), 2000, pp. 761-768
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Hematology,"Cardiovascular & Hematology Research
Journal title
BRITISH JOURNAL OF HAEMATOLOGY
ISSN journal
0007-1048 → ACNP
Volume
108
Issue
4
Year of publication
2000
Pages
761 - 768
Database
ISI
SICI code
0007-1048(200003)108:4<761:COLCIP>2.0.ZU;2-8
Abstract
Recently, we have shown that patients with acute leukaemias and myelodyspla stic syndromes (MDS), who showed increasing mixed chimaerism (MC) upon seri al PCR analysis after transplant, have a significantly increased risk of re lapse. To determine whether the increasing MC in these patients is caused b y the reappearance of normal recipient: haematopoiesis or by the reoccurren ce of malignant cells, we purified different leucocyte subpopulations and a nalysed these subfractions with regard to their donor-recipient ratio by a PCR-based method for the analysis of minisatellite DNA regions. In 14 patie nts [eight acute lymphoblastic leukaemia (ALL), three acute myelogenous leu kaemia (AML) and three MDS] subfractions were analysed when increasing MC w as first noted upon serial analysis of the peripheral blood. In seven of th ese 14 patients (four ALL, two AML and one MDS), subfractions were characte rized at the time of frank haematological relapse, In all 14 patients inves tigated with increasing MC, recipient cells were detected in different mono nuclear cell subpopulations, In patients characterized during frank relapse , two distinct distribution patterns were found. Patients who relapsed befo re day +300 (one ALL, two AML and one MDS) showed recipient-derived (normal ) cells in addition to blast populations in different mononuclear subsets a s well as granulocytes. In patients with acute leukaemias who relapsed afte r day +300 (two ALL and one AML), only leukaemic cells were found that were of recipient origin, whereas all other haematopoietic cell lines were dono r derived. These data show that persistent MC in the early posttransplant period is ca used predominantly by normal recipient haematopoietic cells. This finding f urther supports the hypothesis that a state of mixed haematopoietic chimaer ism may reduce the clinical graft-versus-leukaemia (GVL) effect of alloreac tive donor-derived effector cells in patients with acute leukaemias and MDS , and thus facilitate the proliferation of residual malignant cells that ma y have survived the preparative regimen.