Dynamics in chimerism of T cells and dendritic cells in relapsed CML patients and the influence on the induction of alloreactivity following donor lymphocyte infusion.
Donor lymphocyte infusion (DLI) after allogeneic SCT induces complete remissions in approximately 80% of patients with relapsed CML in chronic phase, but some patients do not respond to DLI. We studied absolute numbers of dendritic cell (DC) subsets and chimerism in T cells and two subsets of blood DCs (myeloid DCs (MDCs) and plasmacytoid DCs (PDCs)) in relation to DLI-induced alloreactivity. Based on T cell and DC chimerism, we identified three groups. Four patients were completely donor chimeric in T cells and DC subsets. These patients had an early stage of relapse, and three of the four patients attained complete molecular remission (CMolR) without significant GVHD. Six patients were completely donor in T cells and mixed chimeric in DC subsets. All patients entered CMolR, but this was associated with GVHD in four and cytopenia in three patients. Five patients had mixed chimerism in T cells and complete recipient chimerism in MDC; only two patients entered CMolR. Our data suggest that the combination of donor T cells and mixed chimerism in DC subsets induces a potent graft-versus-leukemia (GVL) effect in association with GVHD. DLI in patients with an early relapse and donor chimerism in both T cells and DC subsets results in GVL reactivity without GVHD.
Levenga
H
H
Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. t.levenga@hemat.umcn.nl
Woestenenk
R
R
Schattenberg
A V
AV
Maas
F
F
Jansen
J H
JH
Raymakers
R
R
De Mulder
P H M
PH
van de Wiel-van Kemenade
E
E
Schaap
N
N
de Witte
T
T
Dolstra
H
H
D000328:Adult; D000368:Aged; D001782:Blood Donors; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000628:therapy*; D018655:Lymphocyte Count; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction; D013601:T-Lymphocytes / Q000276:immunology*; D018183:Transplantation Chimera / Q000276:immunology*