Differential effect of pre-transplant cytoreduction on recovery of day zero host circulating cells.
Host lymphocytes, reactive against donor specific HLA antigens, emerge at the time of graft rejection following T cell-depleted BMT. Thirty patients receiving different cytoreduction regimens were evaluated for the presence of circulating residual, in vitro expandable, host cells on day 0. Twenty-five patients received TBI-containing regimens and 5 patients received non-TBI containing regimens. Patients prepared with thiotepa or TBI-containing regimens had 10-fold lower numbers of circulating host PBMC pre-transplant on day 0 compared with patients cytoreduced with BU/CY. Cell proliferation was observed only in patients who received BU/CY. The phenotype of the in vitro expanded cells was predominantly CD3+ (88-97%), CD8+ (45-70%), HLA-DR+ (43-88%), although natural killer cell function and phenotype (CD56+: 6-21%) was also documented. Host cells expanded from a patient who received BU/CY exhibited specific cytotoxicity against feeder cell targets, indicating that BU/CY cytoreduction might not be an optimal BMT preparative regimen for patients at high risk of graft failure. The published experience of similar studies to date is also summarized.
Bone Marrow Transplant Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
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V
Papadakis
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S
Mackinnon
N A
NA
Kernan
D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000627:therapeutic use; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008212:Lymphocyte Depletion; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology; D014916:Whole-Body Irradiation
D003520:Cyclophosphamide; D002066:Busulfan