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Minimal residual disease is more common in patients who have mixed T- cell
chimerism after bone marrow transplantation for chronic myelogenous
leukemia
S Mackinnon, L Barnett, G Heller and RJ O'Reilly
Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New
York, NY 10021.
Determining both lymphoid chimerism and the presence of minimal residual
disease after allogeneic bone marrow transplantation (BMT) for chronic
myelogenous leukemia (CML) could be helpful to the understanding of the
biology of leukemic relapse in this disease. We prospectively investigated
32 patients with CML post-BMT by assessing T- cell chimerism and minimal
residual disease using sensitive polymerase chain reaction (PCR)
methodologies. Patients were studied between 1 and 24 months post-BMT.
Thirty patients received a T-cell-depleted marrow grafts and 2 received
unmanipulated marrow. All but 1 patient were conditioned with total body
irradiation (TBI)+thiotepa+cyclophosphamide (Cy). The other patient
received TBI+Cy as conditioning. The T cells were exclusively of donor
origin in 12 of 16 patients who were tested at 1 month post-BMT, but were
mixed chimeric in 11 of these patients by > or = 3 months. Once mixed
T-cell chimerism was documented, no patient returned to having all donor
T-cells. At a median follow-up of 12 months, minimal residual disease was
present in 18 of 22 patients with mixed T-cell chimerism and in 3 of 10
patients with full donor chimerism. The actuarial molecular relapse rate at
24 months for the two groups is 91% and 33%, respectively (P < .02). The
finding of BCR- ABL mRNA within the first 6 months of transplant or on two
consecutive assays was highly predictive of subsequent cytogenetic or
hematologic relapse (P = .032 and P < .02, respectively). Ten patients,
9 with mixed T-cell chimerism, have relapsed (4 clinical, 6 cytogenetic) at
a median of 12 months post-BMT. These data suggest that mixed T-cell
chimerism may be a marker for abrogation of graft-versus-leukemia activity
that is thought to be pivotal in eradicating minimal residual disease after
BMT for CML.
Volume 83,
Issue 11,
pp. 3409-3416,
06/01/1994
Copyright © 1994 by The American Society of Hematology
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