Subject(s)
Blood Platelets/chemistry , Cell Proliferation/drug effects , Immunoglobulins/pharmacology , Killer Cells, Natural/immunology , Multiple Myeloma/immunology , Thalidomide/analogs & derivatives , Culture Media/chemistry , Culture Media/pharmacology , Female , Humans , Immunoglobulins/chemistry , Killer Cells, Natural/pathology , Lenalidomide , Male , Multiple Myeloma/pathology , Thalidomide/pharmacologyABSTRACT
Clinically useful pre-transplant predictive factors of acute graft-versus-host-disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT) are lacking. We prospectively analyzed HSC graft content in CD34+, NK, conventional T, regulatory T and invariant natural killer T (iNKT) cells in 117 adult patients before allo-SCT. Results were correlated with occurrence of aGVHD and relapse. In univariate analysis, iNKT cells were the only graft cell populations associated with occurrence of aGVHD. In multivariate analysis, CD4- iNKT/T cell frequency could predict grade II-IV aGVHD in bone marrow and peripheral blood stem cell (PBSC) grafts, while CD4- iNKT expansion capacity was predictive in PBSC grafts. Receiver operating characteristic analyses determined the CD4- iNKT expansion factor as the best predictive factor of aGVHD. Incidence of grade II-IV aGVHD was reduced in patients receiving a graft with an expansion factor above versus below 6.83 (9.7 vs 80%, P<0.0001), while relapse incidence at two years was similar (P=0.5).The test reached 94% sensitivity and 100% specificity in the subgroup of patients transplanted with human leukocyte antigen 10/10 PBSCs without active disease. Analysis of this CD4- iNKT expansion capacity test may represent the first diagnostic tool allowing selection of the best donor to avoid severe aGVHD with preserved graft-versus-leukemia effect after peripheral blood allo-SCT.
Subject(s)
Graft vs Host Disease/immunology , Hematopoietic Stem Cell Transplantation/adverse effects , Natural Killer T-Cells/immunology , Tissue Donors , Acute Disease , Female , Graft vs Host Disease/diagnosis , Humans , Male , Natural Killer T-Cells/metabolism , Preoperative Period , Prognosis , Severity of Illness Index , Transplantation, HomologousABSTRACT
Promising results of umbilical cord blood transplantation (UCBT) from unrelated donors have been reported in patients with hematologic disorders. These transplants, having potential to trigger beneficial donor-versus-recipient natural killer (NK) cell-mediated alloreaction, we have conducted the first extensive analysis of the phenotypic and functional properties of NK cells after UCBT. NK cells from 25 patients with high-risk hematologic malignancies were compared with cells derived from both healthy adult and CB cells. We found that following UCBT, NK cells display not only some phenotypic features associated with maturity but also unique characteristics that make them fully functional against leukemic blasts. We propose that this full functionality of alloreactive donor-derived NK may drive graft-versus-leukemia reactions after UCBT.
