Detrimental Effect of Natural Killer Cell Alloreactivity in T-replete Hematopoietic Cell Transplantation (HCT) for Leukemia Patients

Joel Y. Sun, Andrew Dagis, Laima Gaidulis, Marcia M. Miller, Roberto Rodriguez, Pablo Parker, Auayporn Nademanee, Peter Falk, Joseph Rosenthal, Stephen J. Forman, David Senitzer
2007 Biology of Blood and Marrow Transplantation  
In hematopoietic cell transplantation (HCT), natural killer cell alloreactivity conferred by inhibitory ligands of killer immunoglobulin-like receptors (iKIRLs) may result in beneficial or detrimental outcomes. More data may contribute to resolution of this complex issue. We analyzed 378 primary allogeneic transplants with T-replete grafts for acute lymphoblastic leukemia (n ‫؍‬ 101), acute myeloid leukemia and myelodysplastic syndrome (n ‫؍‬ 149), and chronic myeloid leukemia (n ‫؍‬ 128). The
more » ... ohort was divided into 3 groups: in group 1, HLA class I matched at the antigen level (n ‫؍‬ 260); in group 2, HLA class I mismatched at the antigen level (n ‫؍‬ 57); and in group 3, HLA class I and iKIRLs mismatched (n ‫؍‬ 61). One-year overall survival (OS) across groups 1 (59%), 2 (49%), and 3 (30%) was significantly different (P ‫؍‬ .002). In contrast to group 2, group 3 had statistically lower OS (P ‫؍‬ .05) and event-free survival (P ‫؍‬ .01). Relapse and relapse-free mortality appeared to contribute to the low OS in group 3. The detrimental effect of natural killer alloreactivity was also evident when HLA-matched transplants were analyzed for patients lacking iKIRLs. One-year OS in patients lacking the HLA-Cw group 1 or 2 iKIRL was significantly lower than that in patients having the iKIRLs (55% vs 67%, n ‫؍‬ 246, P ‫؍‬ .01). Our observations indicate that, in T-replete unrelated HCT, iKIRL mismatches and the absence of iKIRLs confer higher risk to patients after HCT.
doi:10.1016/j.bbmt.2006.09.009 pmid:17241925 fatcat:iqekqnogdbekvh2uuzgnaovxtq