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.
Papadakis
V
V
Bone Marrow Transplant Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Mackinnon
S
S
Kernan
N A
NA
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