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Blood, Vol. 95 No. 12 (June 15), 2000:
pp. 3990-3995
Longitudinal monitoring of immune reconstitution by CDR3 size
spectratyping after T-cell-depleted allogeneic bone marrow transplant
and the effect of donor lymphocyte infusions on T-cell repertoire
Stephanie Verfuerth,
Karl Peggs,
Paulomi Vyas,
Lorna Barnett,
Richard J. O'Reilly, and
Stephen Mackinnon
From the Department of Haematology, University College London,
London, United Kingdom; and Bone Marrow Transplant Service, MSKCC,
New York, NY.
Delayed immune reconstitution after allogeneic bone marrow
transplantation (BMT) with associated infection is a major cause of
morbidity and mortality. We used third complementarity region (CDR3)
size spectratyping as a tool for monitoring T-cell repertoire reconstitution in 19 patients over a median time of 40 months after
T-cell-depleted allogeneic BMT for chronic myeloid leukemia (CML).
Furthermore, the effect of donor lymphocyte infusions (DLI) for the
treatment of relapse in 18 of the 19 patients was analyzed. All BMT
recipients had irregular spectratypes in the first 3- to -6 months
after transplant. These evolved to more normal patterns by 12 months
after transplant and continued to improve thereafter. In approximately
a third of the patients, it took 2 to 3 years for all spectratypes to
normalize, whereas in the other two thirds, some abnormal spectratypes
persisted even after several years. In 9 patients, there was no
immediate change in the CDR3 size profiles after DLI. In 3 patients,
spectratypes improved slightly after DLI, whereas in 6 patients,
spectratypes became more restricted and irregular. Overall, T-cell
spectratypes in BMT patients were characterized by instability over
time and in patients with graft-versus-host disease (GVHD), this was
even more exaggerated. Several factors, such as pre-BMT conditioning,
T-cell depletion of the donor marrow, loss of thymic function in
adults, exposure to infectious agents, GVHD, and immunosuppressive
treatment, are likely contributors to the delay in T-cell-repertoire reconstitution.
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