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Effects of in vitro depletion of T cells in HLA-identical allogeneic marrow
grafts
PJ Martin, JA Hansen, CD Buckner, JE Sanders, HJ Deeg, P Stewart, FR Appelbaum, R Clift, A Fefer and RP Witherspoon
We report results of a pilot study designed to evaluate the effects of in
vitro depletion of T lymphocytes from donor marrow in patients receiving
HLA-identical marrow grafts for treatment of hematologic malignancies.
Twenty patients aged 31 to 50 years were prepared for transplantation with
cyclophosphamide (120 mg/kg) and fractionated total body irradiation (12.0
or 15.75 Gy). All received cyclosporine after grafting. The donor marrows
were treated with a mixture of eight murine monoclonal antibodies and
rabbit serum complement in a manner that achieved a 2- to 3-log depletion
of T cells in most patients. Initial engraftment occurred promptly in 19 of
the patients, and only three had clinically significant acute
graft-versus-host disease. Depletion of donor T cells, however, was
associated with an increased incidence of graft failure, which occurred as
late as 244 days after transplantation. Graft failure was transient in one
patient but apparently was irreversible in seven others. Three of the seven
patients had cytogenetic but not morphological evidence of leukemic relapse
at the time of graft failure. All seven patients with irreversible graft
failure have died, six after receiving second bone marrow transplants.
Seven of the eight cases of graft failure occurred among the 11 patients
prepared for transplantation with 12.0 Gy of total-body irradiation, and
only one occurred among the nine patients with advanced malignancies who
received 15.75 Gy of total-body irradiation. This association with
irradiation dose suggests that host factors were partly responsible for the
graft failures. Because graft failure seldom occurs in irradiated
recipients of unmodified HLA- identical allogeneic marrow transplants, it
appears that T cells in the donor marrow may serve a beneficial function in
helping to maintain sustained engraftment possibly by eliminating host
cells that can cause graft failure. Optimal application of in vitro
manipulation of donor marrow as a method for preventing graft-versus-host
disease will require more effective immunosuppression of the recipient in
order to assure sustained engraftment and function of donor stem cells.
Volume 66,
Issue 3,
pp. 664-672,
09/01/1985
Copyright © 1985 by The American Society of Hematology
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