Longitudinal monitoring of immune reconstitution by CDR3 size spectratyping after T-cell-depleted allogeneic bone marrow transplant and the effect ofdonor lymphocyte infusions on T-cell repertoire

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 media n time of 40 months after T-cell-depleted allogeneic BMT for chronic myeloi d leukemia (CML), Furthermore, the effect of donor lymphocyte infusions (DL I) 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 afte r transplant. These evolved to more normal patterns by 12 months after tran splant 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 se veral 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 instabi lity 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, exp osure to infectious agents, GVHD, and immunosuppressive treatment, are like ly contributors to the delay in T-cell-repertoire reconstitution. (C) 2000 by The American Society of Hematology.